{"schemaVersion":1,"generatedAt":"2026-08-02T20:03:34.691Z","source":{"registry":"ClinicalTrials.gov","apiVersion":"2.0.5","dataTimestamp":"2026-07-31T09:00:04","endpoint":"https://clinicaltrials.gov/api/v2/studies","perQueryLimit":75,"queryCount":69,"coverageNote":"The snapshot stores the most recently updated matches for each tracked peptide query. Registry totals can exceed indexed rows when a query has more matches than the per-query limit."},"stats":{"trials":2643,"recruiting":434,"active":410,"completed":1341,"phase1":384,"phase2":709,"phase3":578,"phase4":373,"companies":194,"countries":96,"averageEnrollment":336,"newestTrial":"NCT07738276","latestResult":"NCT01542021"},"contentHash":"4844e3213143e5daf65f557219565ac6dc1b54b34004e11b7b2d98d255813230","pagination":{"offset":0,"limit":100,"returned":100,"total":2643,"hasMore":true},"links":{"self":"https://www.peptidestat.com/clinical-trials/data?offset=0&limit=100","first":"https://www.peptidestat.com/clinical-trials/data?offset=0&limit=100","previous":null,"next":"https://www.peptidestat.com/clinical-trials/data?offset=100&limit=100"},"trials":[{"nctId":"NCT02115282","title":"Exemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic","officialTitle":"A Randomized Phase III Trial of Endocrine Therapy Plus Entinostat/Placebo in Patients With Hormone Receptor-Positive Advanced Breast Cancer","summary":"This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or another place in the body (metastatic). Estrogen can cause the growth of breast cancer cells. Endocrine therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether exemestane is more effective with or without entinostat in treating breast cancer.","detailedDescription":"PRIMARY OBJECTIVES:\n\nI. To evaluate whether the addition of entinostat to endocrine therapy (exemestane) improves progression-free survival (PFS) and/or overall survival (OS) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have previously progressed on a non-steroidal aromatase inhibitor (Al).\n\nSECONDARY OBJECTIVES:\n\nI. To evaluate the safety and tolerability of entinostat in combination with exemestane, and to compare the safety profile to that of endocrine therapy with placebo.\n\nII. To evaluate the objective response rate of exemestane in combination with entinostat or placebo.\n\nIII. To evaluate whether the efficacy of exemestane with entinostat varies with changes in acetylation status in peripheral blood mononuclear cells (PBMCs).\n\nIV. To evaluate the time to treatment deterioration (as defined by decrease in health-related quality of life \\[HRQL\\], progression, death) of exemestane + entinostat versus exemestane + placebo arms.\n\nV. To evaluate the differences in overall health-related quality of life (HRQL) between the exemestane + entinostat versus exemestane + placebo arms.\n\nVI. To evaluate the difference with respect to specific symptoms that are associated with entinostat, i.e., fatigue, nausea, anorexia and diarrhea, between the exemestane + entinostat versus exemestane + placebo arms.\n\nVII. To measure adherence to protocol therapy. VIII. To evaluate the pharmacokinetics of entinostat in patients with advanced breast cancer.\n\nIX. To evaluate what, if any, patient variables alter the pharmacokinetic profile of entinostat in patients with advanced breast cancer.\n\nEXPLORATORY OBJECTIVES:\n\nI. To collect archival tumor samples and germline deoxyribonucleic acid (DNA) to explore other potential biomarkers of therapeutic efficacy.\n\nII. To collect patient ratings of adverse events (AEs) using select patient-reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items to evaluate the psychometric properties of PRO-CTCAE items and explore the incorporation of PRO-CTCAE items into a phase III double-blind placebo-controlled trial.\n\nOUTLINE: Patients are randomized to 1 of 2 treatment arms.\n\nARM A: Patients receive exemestane orally (PO) once daily (QD) on days 1-28 and entinostat PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline.\n\nARM B: Patients receive exemestane as in Arm A and placebo PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI at baseline, at the end of cycle 3, every 3 cycles, at treatment discontinuation, and during follow-up, collection of blood samples at baseline and day 15 of cycle 1, and collection of archived tissue at baseline.\n\nIn both arms, pre/perimenopausal female patients and all male patients also receive goserelin acetate subcutaneously (SC) on day 1.\n\nAfter completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.","peptideSlugs":["goserelin"],"peptideNames":["Goserelin"],"conditions":["Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Breast Adenocarcinoma","HER2/Neu Negative","Locally Advanced Breast Carcinoma","Metastatic Breast Carcinoma","Recurrent Breast Carcinoma"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":608,"dates":{"start":"2014-03-29","primaryCompletion":"2020-05-05","completion":"2027-06-02","firstPosted":"2014-04-16","resultsPosted":"2021-11-16","lastUpdated":"2026-07-31"},"hasResults":true,"locationCount":654,"countries":["South Africa","United States"],"locations":[{"facility":"University of Alabama at Birmingham Cancer Center","status":null,"city":"Birmingham","state":"Alabama","country":"United States","latitude":33.52066,"longitude":-86.80249},{"facility":"NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro","status":null,"city":"Jonesboro","state":"Arkansas","country":"United States","latitude":35.8423,"longitude":-90.70428},{"facility":"Mercy San Juan Medical Center","status":null,"city":"Carmichael","state":"California","country":"United States","latitude":38.61713,"longitude":-121.32828},{"facility":"Enloe Medical Center","status":null,"city":"Chico","state":"California","country":"United States","latitude":39.72849,"longitude":-121.83748},{"facility":"Adventist Health Cancer Care Center Chico","status":null,"city":"Chico","state":"California","country":"United States","latitude":39.72849,"longitude":-121.83748},{"facility":"Community Cancer Institute","status":null,"city":"Clovis","state":"California","country":"United States","latitude":36.82523,"longitude":-119.70292},{"facility":"University Oncology Associates","status":null,"city":"Clovis","state":"California","country":"United States","latitude":36.82523,"longitude":-119.70292},{"facility":"Eisenhower Medical Center","status":null,"city":"Rancho Mirage","state":"California","country":"United States","latitude":33.73974,"longitude":-116.41279},{"facility":"Mercy Cancer Center - Sacramento","status":null,"city":"Sacramento","state":"California","country":"United States","latitude":38.58157,"longitude":-121.4944},{"facility":"Saint Helena Hospital","status":null,"city":"St. Helena","state":"California","country":"United States","latitude":38.50519,"longitude":-122.47026},{"facility":"Presbyterian Intercommunity Hospital","status":null,"city":"Whittier","state":"California","country":"United States","latitude":33.97918,"longitude":-118.03284},{"facility":"Woodland Memorial Hospital","status":null,"city":"Woodland","state":"California","country":"United States","latitude":38.67852,"longitude":-121.7733},{"facility":"Rocky Mountain Cancer Centers-Aurora","status":null,"city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"The Medical Center of Aurora","status":null,"city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"Boulder Community Foothills Hospital","status":null,"city":"Boulder","state":"Colorado","country":"United States","latitude":40.01499,"longitude":-105.27055},{"facility":"Rocky Mountain Cancer Centers-Boulder","status":null,"city":"Boulder","state":"Colorado","country":"United States","latitude":40.01499,"longitude":-105.27055},{"facility":"Penrose-Saint Francis Healthcare","status":null,"city":"Colorado Springs","state":"Colorado","country":"United States","latitude":38.83388,"longitude":-104.82136},{"facility":"Rocky Mountain Cancer Centers-Penrose","status":null,"city":"Colorado Springs","state":"Colorado","country":"United States","latitude":38.83388,"longitude":-104.82136},{"facility":"UCHealth Memorial Hospital Central","status":null,"city":"Colorado Springs","state":"Colorado","country":"United States","latitude":38.83388,"longitude":-104.82136},{"facility":"AdventHealth Porter","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Colorado Blood Cancer Institute","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Presbyterian - Saint Lukes Medical Center - Health One","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Rocky Mountain Cancer Centers-Midtown","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Saint Joseph Hospital - Cancer Centers of Colorado","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Estrogen receptor (ER) and/or progesterone receptor (PR) positive histologically confirmed adenocarcinoma of the breast with staining of \\>= 1% cells will be considered positive; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)\n* Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) \\>= 2.0, or average HER2 copy number \\>= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)\n* Patients must have measurable or non-measurable stage III/locally advanced or metastatic carcinoma of the breast where local therapy with curative intent is not possible; lesions must be evaluated =\\< 4 weeks prior to study randomization; diagnostic-quality computed tomography (CT) scans with both oral and intravenous (IV) contrast are the expected radiologic method, unless an alternative is approved\n\n  * NOTE: Where baseline imaging has already been performed =\\< 6 weeks prior to study randomization, repeat imaging may not be required\n  * NOTE: As of October 16, 2016, accrual of new patients having non-measurable disease has stopped; the planned accrual for this target population has been reached\n* Pre/peri- and postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:\n\n  * Age \\>= 55 years and one year or more of amenorrhea\n  * Age \\< 55 years and one year or more of amenorrhea, with estradiol \\< 20 pg/ml\n  * Age \\< 55 with prior hysterectomy but intact ovaries, with estradiol \\< 20 pg/ml\n  * Prior bilateral oophorectomy\n\n    * NOTE: Women who do not fit the criteria for being postmenopausal as above are deemed pre-or peri-menopausal; pre/perimenopausal women and all men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; pre/perimenopausal women must have commenced treatment with LHRH agonist at least 4 weeks prior to randomization; if patients have received alternative LHRH agonist prior to study entry, they must switch to goserelin for the duration of the trial\n* Sexually active males and pre/perimenopausal women must agree to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 3 months after discontinuation of therapy\n* Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study =\\< 2 weeks prior to randomization\n\n  * A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Patients must not have known central nervous system metastasis or a history of central nervous system (CNS) metastases; patients with leptomeningeal disease are not eligible\n* Patients must be disease-free of prior invasive malignancies for \\> 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix\n\n  * NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment for that cancer\n* Patients must meet at least one of the following criteria:\n\n  * Disease progression any time after non-steroidal AI use in the advanced disease setting\n  * Relapse while on or within =\\< 12 months of end of adjuvant non-steroidal AI therapy with or without prior endocrine therapy for advanced disease\n  * NOTE: In either setting, treatment with any prior endocrine therapy must be completed \\>= 2 weeks prior to cycle 1 day 1 (C1D1) of study treatment with the exception of exemestane which is permitted in the advanced disease setting within =\\< 4 weeks immediately prior to C1D1; prior adjuvant exemestane is allowed if the disease free interval is \\> 12 months from the discontinuation of exemestane; prior faslodex, everolimus, palbociclib or other cyclin-dependent kinase (CDK) inhibitor (e.g. ribociclib, abemaciclib) use are allowed and must have been completed \\>= 2 weeks prior to C1D1; failure to adhere to this washout guideline will result in a protocol violation\n* Patients may have received only one prior chemotherapy regimen for metastatic disease provided treatment was completed \\>= 3 weeks prior to randomization\n* Patients may be treated with bone modifying agents such as bisphosphonates or RANK-ligand agents (e.g. denosumab) per American Society of Clinical Oncology (ASCO) guidelines; whenever possible, patients requiring bone modifying agents should start treatment \\>= 7 days prior to study therapy and should continue the same agent throughout study unless clinically compelled to change\n* Prior radiotherapy must in general have been completed \\>= 2 weeks prior to randomization and patients must have recovered from the toxicity of the radiation\n\n  * NOTE: Patients may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as sites of measurable or non-measurable disease outside the radiation therapy port are available to follow\n* Patients must NOT receive concurrent anti-cancer therapy or investigational agent unless specified in protocol\n* Patients must NOT be receiving valproic acid, an histone deacetylase (HDAC) inhibitor, and may not have previously received any HDAC inhibitor prior to enrollment (e.g. valproic acid, entinostat, vorinostat) unless discussed with the study chair; patients must not have received prior HDAC therapy for the treatment of their malignancy\n* Patients must have no known allergies to exemestane, entinostat, or medications that have a benzamide structure (e.g., tiapride, remoxipride, clebropride)\n* Patients must NOT suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities; this includes uncontrolled intercurrent illness including, but not limited to ongoing or active infection\n* Patients must have recovered from all clinically relevant adverse events to grade 1 or baseline due to previous agents administered (except alopecia)\n* Patients must have adequate hematologic, liver and renal function =\\< 28 days prior to randomization\n\n  * NOTE: It is preferred that laboratory values for eligibility be assessed after the last dose of prior treatment, especially in cases where most-recent treatment prior to study entry is chemotherapy\n* Hemoglobin (HgB) \\>= 9.0 g/dL (=\\< 28 days prior to randomization)\n* Platelet count \\>= 100,000/mcL (=\\< 28 days prior to randomization)\n* Absolute neutrophil count \\>= 1,500/mcL (=\\< 28 days prior to randomization)\n* Creatinine =\\< 2.0 mg/dL (=\\< 28 days prior to randomization)\n* Total bilirubin \\< 1.5 x institutional upper limit of normal (=\\< 3 mg/dL in case of Gilbert's syndrome) (=\\< 28 days prior to randomization)\n* Transaminases (alanine aminotransferase \\[ALT\\], aspartate aminotransferase \\[AST\\]) =\\< 2.5 x institutional upper limit normal (=\\< 28 days prior to randomization)\n* Known human immunodeficiency virus (HIV)-positive patients should have a cluster of differentiation (CD)4 count \\> 250/mm\\^3\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n* Patients must have a life expectancy \\>= 12 weeks\n* Patients must be able to swallow tablets","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"PROCEDURE","name":"Biospecimen Collection","description":"Undergo collection of blood and archived tissue samples"},{"type":"PROCEDURE","name":"Computed Tomography","description":"Undergo CT"},{"type":"DRUG","name":"Entinostat","description":"Given PO"},{"type":"DRUG","name":"Exemestane","description":"Given PO"},{"type":"DRUG","name":"Goserelin","description":"Given PO"},{"type":"DRUG","name":"Goserelin Acetate","description":"Given SC"},{"type":"PROCEDURE","name":"Magnetic Resonance Imaging","description":"Undergo MRI"},{"type":"OTHER","name":"Placebo Administration","description":"Given PO"},{"type":"OTHER","name":"Quality-of-Life Assessment","description":"Ancillary studies"}],"primaryOutcomes":[{"measure":"Progression-free Survival (PFS)","description":"Progression-free survival (PFS) was defined to be time from randomization to the earliest documented disease progression as defined by the RECIST criteria, new primary breast cancer, or death without progression. Disease assessment was to continue until disease progression, even after non-protocol anti-cancer therapy was started. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of progression, regardless of whether non-protocol anti-cancer therapy was started or not. Disease progression was based on central review, and defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. In addition, the appearance of one or more new lesions was also considered progression. Kaplan-Meier method was used to estimate PFS rate.","timeFrame":"Assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression"},{"measure":"Overall Survival (OS)","description":"Overall survival (OS) was defined to be time from randomization to death from any cause. Cases who were still alive were censored at the date last known alive.","timeFrame":"Assessed every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until death"}],"secondaryOutcomes":[{"measure":"Objective Response Rate (ORR)","description":"Objective response rate was defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses were evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR was defined as disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).","timeFrame":"Assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression"},{"measure":"Time-to-treatment Deterioration (TTD)","description":"Time-to-treatment deterioration (TTD) was defined as time from randomization to disease progression or death or worsening of symptoms, whichever occurred first. Disease progression was assessed per RECIST v1.1. Symptoms deterioration was measured by 6 items (GP1, GP2, GP4, GF7, B1, P2, scored 0-24) from the 8-item FACT-Breast Symptom Index (FBSI). Symptom deterioration was defined as two consecutive available decreases of at least 3 points from baseline using the 6-item FBSI in this trial, and the second visit time was used as the time of symptom deterioration in this case, unless it was the final score, for which one decrease was sufficient. Kaplan-Meier method was used to estimate the median TTD and TTD rate at a certain time point. Symptoms were assessed every cycle for the first six months after randomization, every two cycles between 6 months and 1 year. It then were assessed based on the same schedule for tumor assessments until disease progression as specified below.","timeFrame":"Disease assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression"},{"measure":"Lysine Acetylation Change in CD45 Blood Mononuclear Cells Between C1D1 and C1D15 and PFS in Patients on Arm A","description":"Peripheral blood samples (PBMCs) were collected prior to therapy and on Days 8 and 15 of cycle 1, for assessment of lysine acetylation, using an assay developed by the Trepel Laboratory, NCI/NIH. CD45 blood mononuclear cells were measured. Patients with lysine acetylation change of 1.5 folds or higher were compared to patients with lysine acetylation change of less than 1.5 folds.","timeFrame":"Disease assessed at baseline, then every 12 weeks until treatment discontinuation, then every 3 months within 2 years from study entry, every 6 months between 2-5 years and annually between 6-10 years from study entry, until first disease progression"},{"measure":"Patient-reported Health-related Quality of Life","description":"Health-related quality of life (HRQL) was measured using Functional Assessment of Cancer Therapy - General (FACT-G). The primary endpoint for HRQL was the FACT-G Trial Outcome Index (TOI) which was an aggregate score of 5 items from the FACT-G-Physical subscale (GP2, GP3, GP4, GP6, and GP7) and 6 items from the FACT-G-Functional subscale (GF1, GF2, GF3, GF4, GF6, and GF7). All items were rated on a 5-point Likert scale from 0 to 4. FACT-G TOI subscale score was calculated based on the scoring manual, subscale score ranges from 0 to 44, and higher scores indicate better quality of life. The primary comparison of HRQL between treatment arms was based on the end of cycle 3 assessment.","timeFrame":"Assessed at baseline and end of cycle 3"},{"measure":"Patient-reported Diarrhea","description":"Diarrhea was measured by Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea (FACIT-Diarrhea) subscale form, which had 11 items, all items were rated on a 5-point Likert scale from 0 to 4. FACIT-Diarrhea subscale score was calculated based on the scoring manual, subscale score ranges from 0 to 44, and higher score indicates less diarrhea. The primary comparison of patient-reported diarrhea between treatment arms was based on the end of cycle 3 assessment.","timeFrame":"Assessed at baseline and end of cycle 3"},{"measure":"Patient-reported Fatigue","description":"Fatigue was measured by PROMIS Fatigue short form, it had 7 items and all items were rated on a 5-point Likert scale from 1 to 5. The PROMIS Fatigue total score and T score were calculated based on the scoring manual. The total score ranges from 7 to 35, the T score ranges from 29.4 to 83.2, higher scores indicate more fatigue. The PROMIS Fatigue T score was used for arm comparison. The primary comparison of patient-reported fatigue between treatment arms was based on the end of cycle 3 assessment.","timeFrame":"Assessed at baseline and end of cycle 3"},{"measure":"Patient-reported Nausea and Anorexia","description":"Nausea and anorexia were measured by The Functional Assessment of Anorexia/Cachexia Treatment (FAACT)-additional concerns, which had 12 items, all items were rated on a 5-point Likert scale from 0 to 4. FAACT-additional concerns subscale score was calculated based on scoring manual. Subscale score ranges from 0 to 48, and higher scores indicate less nausea and anorexia. The primary comparison of patient-reported nausea and anorexia between treatment arms was based on the end of cycle 3 assessment.","timeFrame":"Assessed at baseline and end of cycle 3"}],"publications":[{"pmid":"34357781","citation":"Connolly RM, Zhao F, Miller KD, Lee MJ, Piekarz RL, Smith KL, Brown-Glaberman UA, Winn JS, Faller BA, Onitilo AA, Burkard ME, Budd GT, Levine EG, Royce ME, Kaufman PA, Thomas A, Trepel JB, Wolff AC, Sparano JA. E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2021 Oct 1;39(28):3171-3181. doi: 10.1200/JCO.21.00944. Epub 2021 Aug 6."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT02115282"},{"nctId":"NCT02960022","title":"A Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study","officialTitle":"A Phase 2 Open-label Extension Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study","summary":"The purpose of this study is to collect long term safety data in subjects who are continuing to derive clinical benefit from treatment with Enzalutamide from the subjects participation in an enzalutamide clinical study sponsored by Astellas or Medivation (i.e., parent study) which has completed, at a minimum, the primary analysis or the study specified evaluation period.","detailedDescription":"Subjects must continue on the treatment regimen that the subject was receiving in the prior study. Dose changes of any of the prior therapies subjects were receiving on the previous protocol are allowed after medical monitor approval. The day 1 visit for this study should coincide with the last treatment visit for the study the subject will be enrolling from (≤ 7 days post last visit of parent study) unless the subject is on treatment suspension. The subjects will be followed according to the local institution's standard of care and will be required to return to the institution every 24 weeks (± 7 days) to review adverse events (AEs), collect concomitant medications and confirm that no discontinuation criteria are met. At each visit and at every 12 weeks (IP only visit) subjects are to return all dispensed study drug and to receive more study drug if applicable. All AEs (new and ongoing from the study the subject is enrolling from) and Serious Adverse Events (SAEs) (including death), will be collected from the time the subject signs the consent form until the end of study visit.\n\nAfter the marketing approval in South Korea, this study continued as \"post marketing clinical study\" in South Korea. In the rest of the countries which participated in this study, this study continued as clinical study.","peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Prostate Cancer"],"keywords":["prostate cancer","prednisone","MDV3100","enzalutamide","Xtandi","abiraterone acetate"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Astellas Pharma Global Development, Inc.","slug":"astellas-pharma-global-development-inc","class":"INDUSTRY"},"collaborators":[{"name":"Pfizer","slug":"pfizer","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":900,"dates":{"start":"2016-12-22","primaryCompletion":"2029-07-31","completion":"2029-07-31","firstPosted":"2016-11-09","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":241,"countries":["Argentina","Australia","Austria","Belgium","Brazil","Canada","Chile","China","Czechia","Denmark","Finland","France","Georgia","Germany","Hong Kong","Israel","Italy","Japan","Malaysia","Moldova","Netherlands","New Zealand","Norway","Poland","Romania","Russia","Serbia","Slovakia","South Africa","South Korea","Spain","Sweden","Taiwan","Thailand","Turkey (Türkiye)","Ukraine","United Kingdom","United States"],"locations":[{"facility":"Site US10052","status":"COMPLETED","city":"Anchorage","state":"Alaska","country":"United States","latitude":61.21806,"longitude":-149.90028},{"facility":"Site US10011","status":"COMPLETED","city":"Tucson","state":"Arizona","country":"United States","latitude":32.22174,"longitude":-110.92648},{"facility":"Site US10040","status":"COMPLETED","city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Site US10009","status":"COMPLETED","city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Site US10067","status":"RECRUITING","city":"Orange","state":"California","country":"United States","latitude":33.78779,"longitude":-117.85311},{"facility":"Site US10008","status":"COMPLETED","city":"San Bernardino","state":"California","country":"United States","latitude":34.10834,"longitude":-117.28977},{"facility":"Site US10042","status":"COMPLETED","city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Site US10028","status":"COMPLETED","city":"Stanford","state":"California","country":"United States","latitude":37.42411,"longitude":-122.16608},{"facility":"Site US10001","status":"COMPLETED","city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"Site US10017","status":"COMPLETED","city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Site US10050","status":"COMPLETED","city":"Washington D.C.","state":"District of Columbia","country":"United States","latitude":38.89511,"longitude":-77.03637},{"facility":"Site US10049","status":"COMPLETED","city":"Daytona Beach","state":"Florida","country":"United States","latitude":29.21081,"longitude":-81.02283},{"facility":"Site US10048","status":"WITHDRAWN","city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"Site US10002","status":"ACTIVE_NOT_RECRUITING","city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Springfield Clinic, LLP","status":"ACTIVE_NOT_RECRUITING","city":"Springfield","state":"Illinois","country":"United States","latitude":39.80172,"longitude":-89.64371},{"facility":"Site US10007","status":"COMPLETED","city":"Jeffersonville","state":"Indiana","country":"United States","latitude":38.27757,"longitude":-85.73718},{"facility":"University of Kansas Medical Center","status":"ACTIVE_NOT_RECRUITING","city":"Kansas City","state":"Kansas","country":"United States","latitude":39.11417,"longitude":-94.62746},{"facility":"Site US10066","status":"ACTIVE_NOT_RECRUITING","city":"Lenexa","state":"Kansas","country":"United States","latitude":38.95362,"longitude":-94.73357},{"facility":"Site US10029","status":"COMPLETED","city":"Towson","state":"Maryland","country":"United States","latitude":39.4015,"longitude":-76.60191},{"facility":"Site US10032","status":"COMPLETED","city":"St Louis","state":"Missouri","country":"United States","latitude":38.62727,"longitude":-90.19789},{"facility":"Nebraska Medical Hospital","status":"ACTIVE_NOT_RECRUITING","city":"Omaha","state":"Nebraska","country":"United States","latitude":41.25626,"longitude":-95.94043},{"facility":"Site US10023","status":"ACTIVE_NOT_RECRUITING","city":"Omaha","state":"Nebraska","country":"United States","latitude":41.25626,"longitude":-95.94043},{"facility":"Site US10004","status":"ACTIVE_NOT_RECRUITING","city":"Hackensack","state":"New Jersey","country":"United States","latitude":40.88593,"longitude":-74.04347},{"facility":"Site US10024","status":"ACTIVE_NOT_RECRUITING","city":"Garden City","state":"New York","country":"United States","latitude":40.72677,"longitude":-73.6343}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Subject must currently be receiving enzalutamide or assigned to receive enzalutamide (if on treatment suspension) for prostate cancer in a study sponsored by Astellas or Medivation and, based on the investigator's assessment, benefit from continued treatment. Subjects participating in investigator-initiated trials are not eligible.\n* Subject is able to continue on the treatment regimen that they were receiving or were assigned to receive in the prior study. If in the investigator's assessment, a change is needed to the subject's regimen (e.g., dose change in Androgen deprivation therapy (ADT) or dropping of a combination therapy) approval from a medical monitor is required prior to enrollment.\n* Subject is able to swallow enzalutamide capsules and comply with study requirements.\n* Subject and female partner who is of childbearing potential must continue to use 2 forms of birth control, of which 1 must be highly effective and 1 must be a barrier method throughout the study and for 3 months after final enzalutamide administration.\n* Subject agrees to avoid sperm donation during the study and for at least 3 months after final enzalutamide administration.\n* Subject agrees not to participate in another interventional study while on treatment.\n\nCanada Specific:\n\n* Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for the United States sites) must be obtained from the subject prior to any study-related procedures.\n* Subject must currently be receiving enzalutamide for breast cancer in a study sponsored by Astellas or Medivation/Pfizer and based on the investigator's assessment, benefit from continued treatment. Subjects participating in investigator-initiated trials are not eligible.\n* Subject is able to continue on the treatment regimen that they were receiving in the prior study. If in the investigator's assessment, a change is needed to the subject's regimen (e.g., dropping of a combination therapy) approval from a medical monitor is required prior to enrollment.\n* Subject is able to swallow enzalutamide capsules and comply with study requirements.\n* Subject is either:\n* Of nonchildbearing potential:\n* postmenopausal (defined as no spontaneous menses for at least 12 months prior to Day 1 with follicle stimulating hormone (FSH) \\> 40 IU/L at Day 1 for women \\< 55 years of age),\n* documented surgically sterile or status post hysterectomy (at least 1 month prior to Day 1),\n* Or, if of childbearing potential,\n* must have a negative urine pregnancy test at Day 1 before the first dose of study drug is administered,\n* must use 2 acceptable methods of birth control starting at Day 1 and through 6 months after the final study drug administration,\n* must not donate ova starting at first administration of study intervention and throughout 6 months after final study intervention administration.\n\nThe 2 acceptable methods of birth control are as follows or per local guidelines where these require additional description of contraceptive methods:\n\n* A barrier method (e.g., condom by a male partner) is required; AND\n* One of the following is required:\n* Placement of an intrauterine device (IUD) or intrauterine system (IUS);\n* Additional barrier method including occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;\n* Vasectomy or other surgical castration at least 6 months before Day 1.\n* The subject must not be breastfeeding at Day 1 or during the study period, and for 6 months after the final study drug administration.\n* Subject agrees not to participate in another interventional study while on treatment.\n\nExclusion Criteria:\n\n* Subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which subject is enrolling from.\n* Subject requires treatment with or plans to use either of the following:\n\n  * New systemic therapy for subjects cancer (palliative radiation therapy is allowed). The treatment with agents administered during previous studies which was stopped and then restarted during this study does not represent new treatment.\n  * Investigational therapy other than enzalutamide.\n* Subject is currently participating in an investigator-initiated interventional trial and receiving enzalutamide.\n* Subject has any concurrent disease, infection, or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.\n\nCanada Specific:\n\nSubject will be excluded from participation if any of the following apply:\n\n* Subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which they are enrolling from.\n* Subject requires treatment with or plans to use any of the following:\n* New systemic therapy for their cancer (palliative radiation therapy is allowed). The treatment with agents administered during previous studies which was stopped and then restarted during this study does not represent new treatment.\n* Investigational therapy other than enzalutamide.\n* Subject is currently participating in an investigator-initiated interventional trial and receiving enzalutamide.\n* Subject has any concurrent disease, infection, or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.","minimumAge":"18 Years","maximumAge":null,"sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"enzalutamide","description":"Subjects will receive enzalutamide orally once daily at the same time each day."},{"type":"DRUG","name":"abiraterone acetate","description":"Subjects enrolling from study 9785-CL-0011 or MDV3100-10 (PLATO) study may receive abiraterone acetate once daily and prednisone twice daily, in addition to enzalutamide"},{"type":"DRUG","name":"prednisone","description":"Subjects enrolling from study 9785-CL-0011 or MDV3100-10 (PLATO) study may receive abiraterone acetate once daily and prednisone twice daily, in addition to enzalutamide"},{"type":"DRUG","name":"Leuprolide acetate","description":"Subjects enrolling from study MDV3100-13 (EMBARK) study may receive leuprolide acetate once every 12 weeks in addition to enzalutamide once daily"}],"primaryOutcomes":[{"measure":"Number of participants with adverse events","description":null,"timeFrame":"Until End of Study (Up to 96 Months)"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT02960022"},{"nctId":"NCT05669664","title":"Testing the Anti-cancer Drug Darolutamide in Patients With Testosterone-Driven Salivary Gland Cancers","officialTitle":"A Phase 2 Study of Darolutamide in Combination With Leuprolide Acetate in Hormone-Therapy Naive Recurrent and/or Metastatic Androgen Receptor (AR) Positive Salivary Gland Cancer","summary":"This phase II trial tests how well darolutamide and leuprolide acetate work in treating patients with androgen receptor positive salivary cancer that has spread from where it first started (primary site) to other places in the body (metastatic), cannot be removed by surgery (unresectable) or that has come back after a period of responding to prior therapy (recurrent). Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Leuprolide acetate is in a class of medications called gonadotropin-releasing hormone (GnRH) agonists. It works by decreasing the amount of certain hormones in the body. Giving darolutamide in combination with leuprolide acetate may help to stop the growth of tumor cells that need androgens to grow or shrink them.","detailedDescription":"PRIMARY OBJECTIVE:\n\nI. To evaluate the best overall response rate (BOR) of recurrent/metastatic androgen receptor positive (AR+) salivary gland cancer (SGC) patients within one year of darolutamide and androgen deprivation therapy (ADT).\n\nSECONDARY OBJECTIVES:\n\nI. To evaluate progression-free survival (PFS). II. To evaluate overall survival (OS). III. To evaluate toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.\n\nEXPLORATORY OBJECTIVES:\n\nI. To evaluate molecular, genomic and transcriptomic biomarkers in serial research biopsies obtained before and on darolutamide and ADT.\n\nII. To evaluate the differences in BOR, PFS, OS with darolutamide and ADT treatment among patients who did and did not receive prior systemic therapy for AR+ SGC.\n\nOUTLINE:\n\nPatients receive darolutamide orally (PO) twice daily (BID) on days 1-28 of each cycle and leuprolide acetate intramuscularly (IM) every 4 or 12 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, collection of blood samples, and computed tomography (CT)/magnetic resonance imaging (MRI) throughout the trial.\n\nAfter completion of study treatment, patients are followed every 3-6 months for 2 years after treatment discontinuation or until death, whichever occurs first.","peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Locally Advanced Salivary Gland Carcinoma","Metastatic Salivary Gland Carcinoma","Recurrent Salivary Gland Carcinoma","Unresectable Salivary Gland Carcinoma"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":21,"dates":{"start":"2023-07-20","primaryCompletion":"2026-11-30","completion":"2026-11-30","firstPosted":"2023-01-03","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":27,"countries":["United States"],"locations":[{"facility":"UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care","status":null,"city":"Irvine","state":"California","country":"United States","latitude":33.66946,"longitude":-117.82311},{"facility":"Los Angeles General Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"USC / Norris Comprehensive Cancer Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"UC Irvine Health/Chao Family Comprehensive Cancer Center","status":null,"city":"Orange","state":"California","country":"United States","latitude":33.78779,"longitude":-117.85311},{"facility":"University of California Davis Comprehensive Cancer Center","status":null,"city":"Sacramento","state":"California","country":"United States","latitude":38.58157,"longitude":-121.4944},{"facility":"UCHealth University of Colorado Hospital","status":null,"city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"Emory University Hospital Midtown","status":null,"city":"Atlanta","state":"Georgia","country":"United States","latitude":33.749,"longitude":-84.38798},{"facility":"University of Chicago Comprehensive Cancer Center","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"UC Comprehensive Cancer Center at Silver Cross","status":null,"city":"New Lenox","state":"Illinois","country":"United States","latitude":41.51198,"longitude":-87.96561},{"facility":"University of Chicago Medicine-Orland Park","status":null,"city":"Orland Park","state":"Illinois","country":"United States","latitude":41.63031,"longitude":-87.85394},{"facility":"UChicago Medicine Northwest Indiana","status":null,"city":"Crown Point","state":"Indiana","country":"United States","latitude":41.41698,"longitude":-87.36531},{"facility":"Memorial Sloan Kettering Basking Ridge","status":null,"city":"Basking Ridge","state":"New Jersey","country":"United States","latitude":40.70621,"longitude":-74.54932},{"facility":"Memorial Sloan Kettering Monmouth","status":null,"city":"Middletown","state":"New Jersey","country":"United States","latitude":40.39428,"longitude":-74.11709},{"facility":"Memorial Sloan Kettering Bergen","status":null,"city":"Montvale","state":"New Jersey","country":"United States","latitude":41.04676,"longitude":-74.02292},{"facility":"Memorial Sloan Kettering Commack","status":null,"city":"Commack","state":"New York","country":"United States","latitude":40.84288,"longitude":-73.29289},{"facility":"Memorial Sloan Kettering Westchester","status":null,"city":"Harrison","state":"New York","country":"United States","latitude":40.96899,"longitude":-73.71263},{"facility":"Laura and Isaac Perlmutter Cancer Center at NYU Langone","status":null,"city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Memorial Sloan Kettering Cancer Center","status":null,"city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Memorial Sloan Kettering Nassau","status":null,"city":"Uniondale","state":"New York","country":"United States","latitude":40.70038,"longitude":-73.59291},{"facility":"UNC Lineberger Comprehensive Cancer Center","status":null,"city":"Chapel Hill","state":"North Carolina","country":"United States","latitude":35.9132,"longitude":-79.05584},{"facility":"University of Oklahoma Health Sciences Center","status":null,"city":"Oklahoma City","state":"Oklahoma","country":"United States","latitude":35.46756,"longitude":-97.51643},{"facility":"UPMC Hillman Cancer Center","status":null,"city":"Pittsburgh","state":"Pennsylvania","country":"United States","latitude":40.44062,"longitude":-79.99589},{"facility":"UT MD Anderson Cancer Center","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327},{"facility":"Huntsman Cancer Institute/University of Utah","status":null,"city":"Salt Lake City","state":"Utah","country":"United States","latitude":40.76078,"longitude":-111.89105}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed salivary gland cancer that is recurrent/metastatic or unresectable/locally advanced, with AR expression detected by immunohistochemistry (IHC) on a Clinical Laboratory Improvement Act (CLIA)-approved assay. Androgen receptor testing by immunohistochemistry (IHC) can be performed locally in a CLIA (Clinical Laboratory Improvement Amendments) certified lab\n* Patients must have measurable disease\n* Patients must have not had prior AR-targeted therapy, except for AR-targeted therapy administered in the neoadjuvant and/or adjuvant setting and with disease recurrence more than 6 months since treatment completion\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of darolutamide in combination with leuprolide acetate in patients \\< 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\< 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,000/mcL\n* Platelets \\>= 100,000/mcL\n* Total bilirubin =\\< 1.5 x institutional upper limit of normal (ULN) (exception: patients with elevated bilirubin due to Gilbert's disease would be eligible for the trial)\n* Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \\[SGOT\\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\\[SGPT\\]) =\\< 3 x institutional ULN\n* Creatinine =\\< 1.5 x institutional ULN\n* Glomerular filtration rate (GFR) \\>= 30 mL/min/1.73 m\\^2 (by Chronic Kidney Disease Epidemiology Collaboration \\[CKD-EPI\\])\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better\n* The effects of darolutamide on the developing human fetus are unknown. For this reason and because androgen receptor inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic (leuprolide-acetate), women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 days after completion of darolutamide administration or after the depot interval for the leuprolide-acetate dose used has been completed, whichever is longer\n* Ability to understand and the willingness to sign a written informed consent document\n* Patients must have tumors that are safely accessible for biopsy.\n\n  * Note: Two research biopsies are mandated in this trial. If the biopsy is deemed to be unsafe after attempting the first biopsy, the patient will remain eligible for the trial and subsequent tumor biopsies will not be required\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and peripheral neuropathy\n* Patients with a vascular or ischemic event within 6 months of study registration\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to darolutamide or leuprolide acetate\n* Patients on combined P-gp and strong or moderate CYP3A inducers or BCRP substrates are excluded. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with uncontrolled intercurrent illness\n* Pregnant women are excluded from this study because darolutamide is an androgen receptor inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with darolutamide and leuprolide-acetate, breastfeeding should be discontinued if the mother is treated with darolutamide and leuprolide-acetate. These potential risks may also apply to other agents used in this study.\n* Patients with moderate hepatic impairment (Child-Pugh Class B or C)","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"PROCEDURE","name":"Biopsy Procedure","description":"Undergo biopsy"},{"type":"PROCEDURE","name":"Biospecimen Collection","description":"Undergo collection of blood"},{"type":"PROCEDURE","name":"Computed Tomography","description":"Undergo CT"},{"type":"DRUG","name":"Darolutamide","description":"Given PO"},{"type":"DRUG","name":"Leuprolide Acetate","description":"Given IM"},{"type":"PROCEDURE","name":"Magnetic Resonance Imaging","description":"Undergo MRI"}],"primaryOutcomes":[{"measure":"Best overall response (BOR)","description":"The trial will be considered positive if 8 or more complete response/partial response are observed in stage 1 and stage 2 combined.","timeFrame":"Within 1 year of initiating treatment"}],"secondaryOutcomes":[{"measure":"Progression-free survival (PFS)","description":"Will be estimated using Kaplan-Meier methodology. Patients without an event (progression, death) will be censored at the time of last follow-up or last day known to be alive.","timeFrame":"From day 1 of treatment until progression or death, assessed up to 2 years"},{"measure":"Overall survival (OS)","description":"Will be estimated using Kaplan-Meier methodology. Patients without an event (progression, death) will be censored at the time of last follow-up or last day known to be alive.","timeFrame":"From day 1 of treatment until progression or death, assessed up to 2 years"},{"measure":"Incidence of adverse events (AEs)","description":"Will be listed individually per patient according to Common Terminology Criteria for Adverse Events version 5.0, and the number of patients experiencing each AE will be summarized.","timeFrame":"Up to 2 years"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05669664"},{"nctId":"NCT06374875","title":"Fibrosis Lessens After Metabolic Surgery","officialTitle":"A Prospective Multicenter International Randomized Controlled Trial Comparing Surgical and Medical Therapies in the Treatment of Advanced Metabolic Dysfunction Associated Steatohepatitis","summary":"Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment.\n\nPatients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.","detailedDescription":"FLAMES (Fibrosis Lessens After Metabolic Surgery) is a 2-arm randomized, controlled, pathologist-blinded multicenter study with 2 parallel groups of patients with MASH, liver fibrosis, and obesity who will either receive metabolic surgery or incretin-based therapies (semaglutide \\[injection or oral\\], tirzepatide \\[injection\\], or liraglutide \\[injection\\]) for 2 years to assess the effects of advanced surgical and medical therapies in liver histology in patients with obesity, biopsy-proven MASH, and liver fibrosis. With genuine uncertainty in the expert medical community and literature over which treatment will result in a greater improvement in histopathological features of MASH and liver fibrosis, the investigators aim to compare metabolic surgery and incretin-based therapies head-to-head.\n\nAdult patients with BMI between 35 - 60 kg/m\\^2, Fibrosis-4 (FIB-4) index ≥ 1.3, liver stiffness measure (LSM) ≥ 12 kPa by vibration-controlled transient elastography (VCTE) using FibroScan (or similar non-invasive tests) who meet the contemporary eligibility criteria for metabolic surgery will be eligible for participation. Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy. Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point.\n\nThe primary site of this multicenter, international, randomized controlled trial (RCT) is at the Cleveland Clinic main campus in Cleveland, Ohio, USA.","peptideSlugs":["tirzepatide","semaglutide","liraglutide","glucagon"],"peptideNames":["Tirzepatide","Semaglutide","Liraglutide","Glucagon"],"conditions":["Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)","Non-Alcoholic Fatty Liver Disease","Metabolic Dysfunction-Associated Steatohepatitis (MASH)","Liver Fibrosis","Obesity"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"The Cleveland Clinic","slug":"the-cleveland-clinic","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":120,"dates":{"start":"2024-07-11","primaryCompletion":"2029-05-31","completion":"2029-12-31","firstPosted":"2024-04-19","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":22,"countries":["Brazil","Canada","Finland","India","Ireland","Italy","Kuwait","Mexico","Spain","Sweden","Switzerland","United Kingdom","United States"],"locations":[{"facility":"Banner Health Center","status":"NOT_YET_RECRUITING","city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Indiana University","status":"NOT_YET_RECRUITING","city":"Indianapolis","state":"Indiana","country":"United States","latitude":39.76838,"longitude":-86.15804},{"facility":"Mayo Clinic","status":"NOT_YET_RECRUITING","city":"Rochester","state":"Minnesota","country":"United States","latitude":44.02163,"longitude":-92.4699},{"facility":"Cleveland Clinic","status":"RECRUITING","city":"Cleveland","state":"Ohio","country":"United States","latitude":41.4995,"longitude":-81.69541},{"facility":"Hospital Alemão Oswaldo Cruz","status":"RECRUITING","city":"São Paulo","state":null,"country":"Brazil","latitude":-23.5475,"longitude":-46.63611},{"facility":"McGill University","status":"NOT_YET_RECRUITING","city":"Montreal","state":null,"country":"Canada","latitude":45.50884,"longitude":-73.58781},{"facility":"Turku University Hospital","status":"NOT_YET_RECRUITING","city":"Turku","state":null,"country":"Finland","latitude":60.45148,"longitude":22.26869},{"facility":"Sri Aurobindo Institute of Medical Sciences","status":"NOT_YET_RECRUITING","city":"Indore","state":null,"country":"India","latitude":22.71792,"longitude":75.8333},{"facility":"The Digestive Health Institute","status":"NOT_YET_RECRUITING","city":"Mumbai","state":null,"country":"India","latitude":19.07283,"longitude":72.88261},{"facility":"University College Dublin","status":"NOT_YET_RECRUITING","city":"Dublin","state":null,"country":"Ireland","latitude":53.33306,"longitude":-6.24889},{"facility":"Università Cattolica del Sacro Cuore","status":"NOT_YET_RECRUITING","city":"Milan","state":null,"country":"Italy","latitude":45.46427,"longitude":9.18951},{"facility":"Sapienza Università di Roma","status":"NOT_YET_RECRUITING","city":"Roma","state":null,"country":"Italy","latitude":44.99364,"longitude":11.10642},{"facility":"Kuwait University","status":"NOT_YET_RECRUITING","city":"Kuwait City","state":null,"country":"Kuwait","latitude":29.367,"longitude":47.97429},{"facility":"Instituto Nacional de Ciencias Médicas y Nutrición Salvador","status":"NOT_YET_RECRUITING","city":"Mexico City","state":null,"country":"Mexico","latitude":19.42847,"longitude":-99.12766},{"facility":"Hospital Clínic Barcelona","status":"NOT_YET_RECRUITING","city":"Barcelona","state":null,"country":"Spain","latitude":41.38879,"longitude":2.15899},{"facility":"Linköping University","status":"NOT_YET_RECRUITING","city":"Linköping","state":null,"country":"Sweden","latitude":58.41086,"longitude":15.62157},{"facility":"Örebro University","status":"NOT_YET_RECRUITING","city":"Örebro","state":null,"country":"Sweden","latitude":59.27412,"longitude":15.2066},{"facility":"Clarunis Universitäres","status":"NOT_YET_RECRUITING","city":"Basel","state":null,"country":"Switzerland","latitude":47.55839,"longitude":7.57327},{"facility":"Hôpitaux universitaires de Genève","status":"NOT_YET_RECRUITING","city":"Geneva","state":null,"country":"Switzerland","latitude":46.20222,"longitude":6.14569},{"facility":"Nuffield Health Bristol Hospital","status":"NOT_YET_RECRUITING","city":"Bristol","state":null,"country":"United Kingdom","latitude":51.45523,"longitude":-2.59665},{"facility":"King's College Hospital","status":"NOT_YET_RECRUITING","city":"London","state":null,"country":"United Kingdom","latitude":51.50853,"longitude":-0.12574},{"facility":"Queen Mary University","status":"NOT_YET_RECRUITING","city":"London","state":null,"country":"United Kingdom","latitude":51.50853,"longitude":-0.12574}],"eligibility":{"criteria":"Inclusion Criteria\n\nEntry into the study would require that the patient:\n\n1. Is a candidate for general anesthesia\n2. Is eligible for metabolic surgery (RYGB or SG) based on the ASMBS/IFSO 2022 guidelines\n3. Has insurance coverage for metabolic surgery (the requirements may vary in each country)\n4. Is ≥18 and ≤75 years old at the time of signing the informed consent\n5. Has a BMI ≥35 and ≤70 kg/m2 at the time of first study visit\n6. FIB-4 ≥ 1.3\n7. At least one of the following 5 criteria suggesting presence of advanced fibrosis:\n\n   * LSM ≥ 12 kPa by VCTE using FibroScan®\n   * LSM ≥ 12 kPa by SWE\n   * LSM ≥ 1.7 m/s by ARFI\n   * LSM ≥ 3.63 kPa MRE\n   * ELF score ≥ 9.8\n8. Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication (including insulin but not semaglutide or tirzepatide or liraglutide) for at least 3 months prior to entry, with glycated hemoglobin (HbA1c) ≤12%.\n9. Self-reported stable weight in 6 months before the first study visit (no weight loss \\>10% within 6 months prior to the first study visit)\n\n   a. In patients with a historical noninvasive tests or liver biopsy, weight loss of no more than 10% is allowed from 6 months prior to the historical tests until the first study visit\n10. Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study\n11. Can understand the options and comply with the requirements of each arm, including one liver biopsy performed during the screening period (if no adequate biopsy within 12 months before screening is available) and one liver biopsy after 2-years\n12. Has a negative urine pregnancy test at the first and at the randomization visits for women of childbearing potential.\n13. Women of childbearing age must agree to use reliable method of contraception for 2 years\n\n8.2 Exclusion Criteria\n\nPatients who meet the following criteria will be excluded from the study:\n\n1. Known history of other chronic liver diseases (drug induced, viral hepatitis, autoimmune, and genetic):\n\n   * Hepatitis B as detected by presence of hepatitis B surface antigen (HBsAg)\n   * Hepatitis C as detected by presence of hepatitis C virus (HCV) RNA (in case the screening test for hepatitis C is positive, the confirmative test is decisive)\n   * Autoimmune liver disease as diagnosed by antibodies or compatible liver histology\n   * Primary biliary cirrhosis as defined by the presence of at least 2 criteria (elevated alkaline phosphatase, presence of anti-mitochondrial antibody, and histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts)\n   * Primary sclerosing cholangitis\n   * Wilson's disease as diagnosed by low ceruloplasmin or compatible liver histology\n   * Alpha-1-antitrypsin deficiency as diagnosed by alpha1-antitrypsin level or liver histology\n   * Hemochromatosis as diagnosed by HFE mutations (C282Y, H63D), ferritin and transferrin saturation levels, or presence of 3+ or 4+ stainable iron on liver biopsy\n   * Drug-induced liver disease diagnosed by medical history\n   * Known bile duct obstruction\n   * Suspected or proven liver cancer\n2. Weight change \\>10% within 6 months prior to the first study visit or prior to the historical liver biopsy\n3. Treatment with semaglutide, tirzepatide, or liraglutide (for obesity or for T2DM) \\<90 days before the first study visit.\n\n   • However, patients are allowed to participate if they have been on a low dose (or are on older generation GLP-1 agonists) and have lost less than 10% of their body weight since starting the medication.\n4. Type 1 diabetes or autoimmune diabetes\n5. Known cases of human immunodeficiency virus infection\n6. Prior bariatric and metabolic surgery of any kind\n\n   • Reversed procedures such as gastric band or intragastric balloon that have been removed at least 3 months prior to the first study visit are allowed.\n7. Prior complex foregut surgery including any esophageal and gastric surgeries, anti-reflux procedures, biliary diversion, and complex trauma surgery\n8. Any surgery requiring general anesthesia within 1 month prior to signing the consent\n9. History of solid organ transplant\n10. Severe pulmonary disease defined as FEV1 \\< 50% of predicted value\n11. Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)\n12. Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V\n13. Classified as New York Heart Association Class IV\n14. Left ventricular ejection fraction \\<25% at the time of screening\n15. Myocardial infarction, unstable angina, stroke, heart surgery, coronary stent placement in the past 6 months\n16. Chronic renal insufficiency with eGFR below 30 mL/min/1.73 m2, or being on dialysis\n17. Presence of large hiatal hernia (\\>7 cm)\n18. Presence of Crohn's disease\n19. Psychiatric disorders including (but not limited to) dementia, active psychosis, severe depression requiring 3 or more medications, history of suicide attempts, active alcohol, or substance abuse within the previous 12 months that in the opinion of the investigators could disqualify the patient from metabolic surgery\n20. Pregnancy, the intention of becoming pregnant, or not using adequate contraceptive measures\n21. Breastfeeding\n22. Diagnosis of malignancy within the preceding 3 years (except squamous cell and basal cell cancer of the skin)\n23. Anemia defined as hemoglobin less than 9 g/dL\n24. On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs)\n25. Known history of clotting disorders, including pulmonary embolus and deep vein thrombosis\n26. Clinical judgment that life expectancy is less than 3 years\n27. Use of investigational therapy within 3 months prior to signing the consent\n28. History of pancreatic carcinoma\n29. Acute pancreatitis \\< 180 days before screening\n30. History or presence of chronic pancreatitis\n31. Presence of concerning thyroid nodule\n32. Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) \\> 6.0 mIU/L or \\< 0.1 mIU/L before the first study visit\n\n    * Patients receiving treatment for hypothyroidism can be included if their thyroid hormone replacement dose has been stable for at least 3 months.\n    * Patients whose TSH is outside the rang but they have normal levels of thyroid hormones can be included.\n33. A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)\n34. Evidence or history of ascites or spontaneous bacterial peritonitis that require(d) treatment\n\n    • Trace ascites identified only by an abdominal imaging without other evidence of clinically significant portal hypertension and esophageal varices is not an exclusion criterion.\n35. Evidence or history of hepatic encephalopathy\n36. Evidence or history of variceal bleeding\n37. Evidence or history of portosplenic vein thrombosis\n38. Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to the first study visit.\n\n    • Defined as more than 14 units/week for females (\\>1 drink per day) and more than 21 units/week for males (\\>2 drinks per day) on average, where one unit of alcohol is equivalent to a 12-oz beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor.\n39. Treatment with medications (for more than 14 consecutive days) with known effect on liver steatosis (e.g., treatment with systemic corticosteroids \\[oral or intravenous\\], methotrexate, tamoxifen, valproic acid, amiodarone, or tetracycline) in the 3 months prior to the first study visit (or historical liver biopsy).\n40. ALT or AST or Alkaline phosphatase \\>200 U/L\n41. Recurrent major hypoglycemia or hypoglycemic unawareness\n42. Inability to safely obtain a liver biopsy\n43. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study\n44. Unable to understand the risks, benefits, and compliance requirements of study\n45. Lack capacity to give informed consent\n46. Plans to move outside the primary location of study (country) within the next 24 months\n47. Known or suspected allergy to semaglutide, tirzepatide, liraglutide, excipients, or related products\n48. Previous participation in this trial and got randomized to one of the study groups but did not proceed.\n49. Hospitalization due to COVID-19 within 2 months prior to screening.\n50. Platelet count \\<80,000\n51. International Normalized Ratio (INR) \\>1.7\n52. Child-Pugh score B or C\n53. MELD score ≥15\n54. Upper endoscopy showing gastroesophageal varices\n55. Upper endoscopy showing more than mild portal hypertensive gastropathy\n56. Liver vascular ultrasound (duplex ultrasonography) showing significant portal hypertension characterized by dilated portal vein (\\>13 mm), biphasic or reverse flow in the portal vein, enlarged paraumbilical veins, splenorenal collaterals, or dilated left and short gastric veins.\n\n    Note: Negative findings on upper endoscopy and liver duplex ultrasound (done within one year of the first study visit for both tests) are necessary to establish eligibility for the FLAMES.\n    * Ruling out clinically significant portal hypertension is particularly important in patients with a liver stiffness ≥20 kPa or with a platelet count \\<150,000 per μL or with a (historical) liver biopsy showing cirrhosis.\n    * A subset of patients without having upper endoscopy and liver duplex ultrasound can be eligible for enrollment if their:\n\n      * liver stiffness (by transient elastography using FibroScan®) is between 12 and 15 kPa and their platelet count is \\>150,000 per μL, or\n      * a (historical) liver biopsy showing absence of cirrhosis, or\n      * a (historical) HVPG \\< 5 mmHg\n57. Cross-sectional abdominal imaging (if available historically) indicating presence of large portosystemic collaterals or ascites\n\n    • Splenomegaly alone (in the absence of other radiological and laboratory findings) is not considered to be a sign of clinically significant portal hypertension and is not an exclusion criterion.\n58. HVPG ≥ 12 mmHg (if available historically or if measured at the time of de novo liver biopsy)\n59. Liver biopsy characteristics:\n\n    * F0 in de novo biopsy; Enrollment cap of 20% for F1 in de novo biopsy.\n    * F0 and F1 in historical liver biopsy\n    * Absence of all three components of MASH (steatosis, hepatocyte ballooning, and lobular inflammation) in patients with F1, F2, and F3\n    * Absence of steatosis (\\<5%) in patients with F4\n    * Diagnosis other than MASH","minimumAge":"18 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"PROCEDURE","name":"Metabolic surgery","description":"Patients receive either RYGB or SG. The surgical risk, differential impact of each procedure on body weight and other obesity-related diseases, presence of other medical and mental problems, patient's behavioral factors (e.g., postoperative compliance, active smoking), medications, and goals will be considered when the patient and local medical team make a shared decision about the most appropriate surgical procedure"},{"type":"DRUG","name":"Incretin-Based Therapy","description":"Three incretin-based medications that have been approved for treatment of obesity including liraglutide, semaglutide, or tirzepatide will be used in the nonsurgical group. Any of these 3 medications (in the injection or oral from) based on availability in each country, access, and clinical indications can be used. If possible, patients will be placed on high-dose tirzepatide (Mounjaro or Zepbound 15 mg once weekly injection) or high-dose semaglutide (Wegovy 2.4 mg once weekly injection or Ozempic 2 mg once weekly injection). Other acceptable, less preferrable, options: liraglutide (Saxenda or Victoza), semaglutide tablet (Rybelsus), or lower dose of tirzepatide and semaglutide injections."}],"primaryOutcomes":[{"measure":"Improvement of at least 1 fibrosis stage of the Kleiner fibrosis classification and no worsening of MASH in the repeat liver biopsy.","description":"Development of hepatic decompensation events including ascites (requiring treatment including diuretics), spontaneous bacterial peritonitis, hepatic encephalopathy (requiring treatment or hospitalization), or bleeding esophageal varices, and all-cause mortality will be counted as a treatment failure with no need for repeating liver biopsy.","timeFrame":"Through study completion, 2 years"}],"secondaryOutcomes":[{"measure":"MASH resolution in the repeat liver biopsy","description":"MASH resolution defined as no hepatocyte ballooning (score of 0 according to the NASH CRN criteria), no more than mild residual inflammatory cells (score of 0 or 1), without worsening of liver fibrosis stage in the repeat liver biopsy","timeFrame":"Through study completion, 2 years"},{"measure":"MASH resolution and fibrosis improvement in the repeat liver biopsy","description":"Presence of both MASH resolution and fibrosis improvement in the repeat liver biopsy","timeFrame":"Through study completion, 2 years"},{"measure":"Fibrosis progression in the repeat liver biopsy","description":"Defined as worsening of at least 1 fibrosis stage of the Kleiner fibrosis classification in the repeat liver biopsy among patients who did not have F4 in the baseline liver biopsy","timeFrame":"Through study completion, 2 years"},{"measure":"Average Weight loss percentage","description":"Mean percentage weight loss from baseline","timeFrame":"Through study completion, 2 years"},{"measure":"Disease-specific Quality of Life (QoL)","description":"Change from baseline in score of a disease-specific QoL instrument: Chronic Liver Disease Questionnaire (CLDQ) for NASH (CLDQ-NASH). This instrument collects data on 36 items grouped into 6 domains: abdominal symptoms, activity/energy, emotional health, fatigue, systemic symptoms, and worry. In all domains, greater scores (between 1-7) reflect better health, and the average of the domain scores yields the total CLDQ-NASH score. Research coordinator completes the survey with the patient.","timeFrame":"Through study completion, 2 years"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06374875"},{"nctId":"NCT06987513","title":"RECLAIM STUDY: Phase 2 Study of the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol Use Disorder (AUD) in Subjects With Obesity or Overweight","officialTitle":"RECLAIM STUDY: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol Use Disorder (AUD) in Subjects With Obesity or Overweight","summary":"This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pemvidutide in the treatment of AUD in subjects with obesity or overweight. After signing the informed consent form, subjects will be screened and if eligible randomized 1:1 to 1 of the following 2 treatment arms:\n\n* Pemvidutide: 2.4 mg SC once weekly\n* Placebo: Placebo SC once weekly","detailedDescription":null,"peptideSlugs":["pemvidutide"],"peptideNames":["Pemvidutide"],"conditions":["Alcohol Use Disorder (AUD)"],"keywords":["Pemvidutide","GLP-1 receptor agonist","Alcohol Use Disorder","Obesity","Overweight","AUD treatment","Phase 2"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Altimmune, Inc.","slug":"altimmune-inc","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":100,"dates":{"start":"2025-05-15","primaryCompletion":"2026-07-30","completion":"2026-07-30","firstPosted":"2025-05-23","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":12,"countries":["United States"],"locations":[{"facility":"Altimmune Clinical Study Site","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"Altimmune Clinical Study Site","status":null,"city":"New Haven","state":"Connecticut","country":"United States","latitude":41.30815,"longitude":-72.92816},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Fort Myers","state":"Florida","country":"United States","latitude":26.62168,"longitude":-81.84059},{"facility":"Altimmune Clinical Study Site","status":null,"city":"University Park","state":"Florida","country":"United States","latitude":25.74649,"longitude":-80.36755},{"facility":"Altimmune Clinical Study Site","status":null,"city":"North Canton","state":"Ohio","country":"United States","latitude":40.87589,"longitude":-81.40234},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Tulsa","state":"Oklahoma","country":"United States","latitude":36.15398,"longitude":-95.99277},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Providence","state":"Rhode Island","country":"United States","latitude":41.82399,"longitude":-71.41283},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Charleston","state":"South Carolina","country":"United States","latitude":32.77632,"longitude":-79.93275},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Charlottesville","state":"Virginia","country":"United States","latitude":38.02931,"longitude":-78.47668},{"facility":"Altimmune Clinical Study Site","status":null,"city":"Richmond","state":"Virginia","country":"United States","latitude":37.55376,"longitude":-77.46026}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Written informed consent signed prior to performance of any study procedures\n2. Male or female ages 18 to 75 years, inclusive\n3. Diagnosis of current AUD of moderate or greater severity according to DSM-5 criteria\n4. Reported drinking at least 28 drinks per week if male or 21 drinks per week if female in the 28 days prior to signing the informed consent. This should include at least 3 heavy drinking days per week (defined as ≥ 5 drinks per day for men and ≥ 4 drinks per day for women) Note: Baseline heavy drinking days will be determined by the TFLB method (28-day recall) drinking pattern collected at the initial screening visit\n5. Overweight or obesity, defined as BMI ≥ 25 kg/m2\n\nExclusion Criteria:\n\n1. Presence of clinically significant alcohol withdrawal symptoms, as defined as CIWA-Ar score ≥ 10 at screening and/or prior to randomization\n2. History of hospitalization for alcohol intoxication or alcohol withdrawal\n3. History of alcohol-related disorders including seizures related to alcohol, MalloryWeiss Syndrome, and alcoholic ketoacidosis\n4. History and/or current DSM-5 diagnosis of schizophrenia, bipolar disorder, psychotic disorder or other severe psychiatric disorders, unless documented as well-controlled by the Investigator and cleared by the Medical Monitor\n5. C-SSRS score indicative of active suicidal thoughts (answering \"yes\" to any of Questions 2 through 5 on the C-SSRS) in the past 6 months","minimumAge":"18 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Pemvidutide","description":"Pemvidutide 2.4 mg SC once weekly"},{"type":"OTHER","name":"Placebo","description":"Placebo SC once weekly"}],"primaryOutcomes":[{"measure":"Change from baseline in the average number of heavy drinking days per week","description":"Change from baseline in the average number of heavy drinking days per week, with a heavy drinking day defined as 5 or more drinks in the day for men and 4 or more drinks in the day for women, using the Timeline Followback (TLFB) method","timeFrame":"Baseline to Weeks 21-24"}],"secondaryOutcomes":[{"measure":"Proportion of subjects achieving a 2-level reduction in WHO risk drinking level","description":"Proportion of subjects achieving a 2-level reduction in WHO risk drinking level using the TLFB method for the 4-week period comprising Weeks 21 through 24","timeFrame":"Baseline to Weeks 21-24"},{"measure":"Absolute change from baseline in average phosphatidylethanol (PEth) levels at Week 24","description":null,"timeFrame":"Baseline to Week 24"},{"measure":"Change from baseline in average number of drinks per drinking day","description":"Change from baseline in average number of drinks per drinking day using the TLFB method for the 4-week period comprising Week 21 through 24","timeFrame":"Baseline to Weeks 21-24"},{"measure":"Change from baseline in proportion of subjects achieving no heavy drinking days","description":"Change from baseline in proportion of subjects achieving no heavy drinking days using the TLFB method for the 4-week period comprising Week 21 through 24","timeFrame":"Baseline to Weeks 21-24"},{"measure":"Change from baseline in average percent days completely abstinent","description":"Change from baseline in average percent days completely abstinent using the TLFB method for the 4-week period comprising Week 21 through 24","timeFrame":"Baseline to Weeks 21-24"},{"measure":"Change from baseline at Week 24 in average Drinker Inventory of Consequences - Short Inventory of Problems (DrInc-SIP-2R)","description":null,"timeFrame":"Baseline to Week 24"},{"measure":"Change from baseline at Week 24 in Patient Reported Outcomes Measurement Information System (PROMIS) Negative Alcohol Consequences (NECO) Short Form","description":null,"timeFrame":"Baseline to Week 24"},{"measure":"Percent changes from baseline in body weight","description":null,"timeFrame":"Baseline to Week 24"},{"measure":"Percent change from baseline in BMI","description":null,"timeFrame":"Baseline to Week 24"},{"measure":"Percent change from baseline in waist circumference","description":null,"timeFrame":"Baseline to Week 24"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06987513"},{"nctId":"NCT07478653","title":"MODERN-Dental: Pediatric Obesity, Cardiometabolic Risks, And Periodontal Disease","officialTitle":"MODERN-Dental: Pediatric Obesity, Cardiometabolic Risks, And Periodontal Disease: Effects Of Semaglutide Treatment","summary":"The goal of this clinical trial is to assess whether adjunctive dental cleaning can enhance the effects of semaglutide in children with obesity. The main question\\[s\\] it aims to answer \\[is/are\\]:\n\nif dental cleaning will improve both oral health and metabolic outcomes beyond the effects of semaglutide alone.\n\nParticipants will receive either dental cleaning and oral hygiene instruction or oral hygiene instruction alone.","detailedDescription":"Parent study NCT06967389","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Obesity","Dental Care for Children"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Oelisoa Andriankaja","slug":"oelisoa-andriankaja","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":50,"dates":{"start":"2026-09-01","primaryCompletion":"2028-07-31","completion":"2028-07-31","firstPosted":"2026-03-17","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"University of Kentucky","status":null,"city":"Lexington","state":"Kentucky","country":"United States","latitude":37.98869,"longitude":-84.47772}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* participants from the ongoing Mitigation of Cardiovascular Disease Risks in Children with Extreme Obesity (MODERN) study (NCT06967389)\n* Class 2 or 3 obesity (BMI =120% of the 95th percentile for age and sex)\n\nExclusion Criteria:\n\n* Same exclusion as parent study.\n* Planning to receive or complete dental services during the 12-month course of the study\n* Ongoing orthodontic treatment\n* Use of any anti-inflammatory medication (other than steroids) within 1 month prior to enrollment\n* Currently taking medications that could influence the characteristics or response to periodontal treatment (e.g., use of immunosuppressants or steroids)\n* Local or systemic antibiotic use within 15 days prior to enrollment or for \\>10 days within the past 3 months\n* History of bleeding disorders\n* Professional dental prophylaxis or non-surgical periodontal therapy within the past 6 months","minimumAge":"12 Years","maximumAge":"17 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"PROCEDURE","name":"Dental Cleaning and Oral Hygiene Instruction (OHI)","description":"Participants receive dental cleaning and oral hygiene instruction (OHI) and oral health assessments at baseline (prior to initiating weight-loss medication), 6 months (±2 weeks), and 12 months (±1 month) post-enrollment."},{"type":"BEHAVIORAL","name":"Oral Hygiene Instruction (OHI)","description":"Participants will receive standard oral health care, including instructions on how to care for their teeth (OHI). Dental cleaning provided at 12 months."}],"primaryOutcomes":[{"measure":"Change in gingival index","description":"Based on visual assessment and gentle probing of the marginal periodontal tissues. Scored on a 0-3 scale and the higher score means increased inflammation.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in probing depth","description":"Measuring the pocket depth at six sites per tooth (in millimeters) using a UNC-15 periodontal probe.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in BOP (Bleeding on probing)","description":"Presence or absence of bleeding upon probing recorded at six sites per tooth.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in Plaque Index","description":"Measured using a plaque score (0-3) at six specific Ramfjord teeth","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in Clinical Attachment Level (CAL)","description":"Calculated as PD (Pocket Depth) + GM (Gingival Margin) for each site.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in Gingival Margin Position (GM)","description":"Recorded at six sites per tooth (in millimeters) using a UNC-15 periodontal probe.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Number of participants with Supragingival and Subgingival Calculus","description":"Recorded as present or absent, generalized or localized when visible or detected upon probing.","timeFrame":"Baseline, 6 months, 12 months"},{"measure":"Change in Gingival Crevicular Fluid (GCF)","description":"Up to six samples per participant using Periopaper strips at mesiobuccal interproximal sites.","timeFrame":"Baseline, 6 months, 12 months"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07478653"},{"nctId":"NCT07619989","title":"Transcutaneous Auricular Vagus Nerve Stimulation for Poor Weight-Loss Response to Incretin Receptor Agonists","officialTitle":"Adjunctive Transcutaneous Auricular Vagus Nerve Stimulation in Overweight or Obese Patients With a Suboptimal Weight-Loss Response to Incretin Receptor Agonists: A Single-Center, Randomized, Sham-Controlled Study","summary":"This is a single-center, randomized, participant-blinded, sham-controlled trial designed to evaluate the adjunctive effect of transcutaneous auricular vagus nerve stimulation (taVNS) in overweight or obese patients who show a suboptimal weight-loss response to incretin receptor agonist therapy. A total of 24 participants will be randomly assigned to receive either taVNS plus tirzepatide 5 mg or sham stimulation plus tirzepatide 5 mg for 12 weeks. The primary objective is to compare the percent change in body weight from baseline to week 12 between the two groups.","detailedDescription":"This is a prospective, single-center, randomized, participant-blinded, sham-controlled, parallel-group study conducted at the Department of Endocrinology, Nanjing Drum Tower Hospital. The study will enroll 24 overweight or obese participants with a suboptimal weight-loss response, defined as a body weight reduction of no more than 10% after at least 12 weeks of tirzepatide treatment. Eligible participants will be randomized in a 1:1 ratio to the taVNS plus tirzepatide 5 mg group or the sham stimulation plus tirzepatide 5 mg group for 12 weeks.\n\nBefore and after intervention, all participants will undergo standardized assessments, including lifestyle questionnaires, anthropometric measurements, body composition analysis, autonomic function evaluation, laboratory testing, and assessment of hepatic steatosis and fibrosis. Autonomic function assessment will include heart rate variability, cardiovascular autonomic reflex tests, sudomotor function, and brain MRI. Liver-related assessments will include FibroTouch and liver MRI. During follow-up, body weight will be monitored weekly by telephone or WeChat, waist circumference, hip circumference, and body composition will be reassessed every 4 weeks, and device use will be monitored through an app to ensure adherence and protocol consistency.\n\nThe primary endpoint is the between-group difference in percent change in body weight from baseline to week 12. Secondary endpoints include changes in body composition and fat distribution, glucose- and lipid-related metabolic parameters, liver function and hepatic steatosis/fibrosis-related parameters, and autonomic function measures. Exploratory analyses will evaluate changes in brain imaging phenotypes after 12 weeks of intervention.","peptideSlugs":["tirzepatide"],"peptideNames":["Tirzepatide"],"conditions":["Obesity & Overweight"],"keywords":["Obesity & Overweight","Transcutaneous Auricular Vagus Nerve Stimulation","Incretin Receptor Agonists","Non-responders"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School","slug":"the-affiliated-nanjing-drum-tower-hospital-of-nanjing-university-medical-school","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":24,"dates":{"start":"2026-08-01","primaryCompletion":"2027-06-01","completion":"2027-09-01","firstPosted":"2026-06-02","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":1,"countries":["China"],"locations":[{"facility":"Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School","status":"RECRUITING","city":"Nanjing","state":"Jiangsu","country":"China","latitude":32.06167,"longitude":118.77778}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Individuals with obesity, or overweight accompanied by at least one weight-related comorbidity (e.g., hypertension or fatty liver disease), who have been receiving tirzepatide therapy for at least 12 weeks and have achieved ≤10% weight loss during treatment;\n2. Willingness to provide written informed consent.\n\nExclusion Criteria:\n\n1. Presence of diseases that may substantially affect body weight homeostasis, including Cushing's syndrome, uncontrolled thyroid disease (thyroid-stimulating hormone \\>6.0 mIU/L or \\<0.4 mIU/L), malignancy, or similar conditions;\n2. Use within the past 3 months of medications, other than incretin receptor agonists, that may significantly affect body weight, including glucocorticoids and antipsychotic agents;\n3. Skin infection or damage involving the auricular area;\n4. Women planning pregnancy in the near future;\n5. Contraindications to MRI, such as metallic prostheses or claustrophobia;\n6. Diagnosis of diabetes mellitus; Inability to complete the 12-week intervention period for practical reasons, such as frequent business travel or planned travel.","minimumAge":"18 Years","maximumAge":"50 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DEVICE","name":"transcutaneous auricular vagus nerve stimulation","description":"Participants will receive active transcutaneous auricular vagus nerve stimulation plus tirzepatide 5 mg for 12 weeks. Active stimulation will be delivered to the bilateral cymba conchae, an auricular region innervated by the auricular branch of the vagus nerve. Stimulation will use an intermittent waveform of 15 seconds on and 5 seconds off at 20 Hz, with a pulse width of 0.2 ms. Stimulation intensity will be titrated from 0 mA to a level that produces mild tingling without obvious discomfort, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes per session, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly."},{"type":"DEVICE","name":"Sham","description":"Participants will receive sham stimulation in addition to tirzepatide 5 mg for 12 weeks. Sham stimulation will be applied to the bilateral tail of the helix, an auricular site without vagus nerve distribution, whereas active taVNS targets the cymba conchae, which is innervated by the auricular branch of the vagus nerve. The sham group will use the same waveform parameters, stimulation intensity titration, and treatment schedule as the active group, namely twice daily for 30 minutes per session, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly."}],"primaryOutcomes":[{"measure":"Percent Change in Body Weight From Baseline","description":"Percent change in body weight from baseline to week 12 will be compared between the taVNS plus tirzepatide group and the sham stimulation plus tirzepatide group to evaluate the adjunctive effect of taVNS on weight reduction.","timeFrame":"Baseline, 4 weeks, 8 weeks, 12 weeks"}],"secondaryOutcomes":[{"measure":"Change in Waist Circumference","description":"Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement.","timeFrame":"Baseline, Week 4, Week 8, Week 12"},{"measure":"Change in Body Composition and Fat Distribution","description":"Changes in body composition and fat distribution will be assessed by body fat percentage using anthropometric measurements and body composition analysis.","timeFrame":"Baseline, ,Week 4, Week 8, Week 12"},{"measure":"Change in blood glucose","description":"Change in fasting blood glucose from baseline to Week 12 will be assessed using laboratory testing.","timeFrame":"Baseline, Week 12"},{"measure":"Change in Hip Circumference","description":"Change in hip circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement.","timeFrame":"Baseline, Week 4, Week 8, Week 12"},{"measure":"Change in Visceral Fat Area","description":"Change in visceral fat area from baseline to Week 4, Week 8, and Week 12 will be assessed using body composition analysis.","timeFrame":"Baseline, Week 4, Week 8, Week 12"},{"measure":"Change in Glycated Hemoglobin","description":"Change in glycated hemoglobin (HbA1c) from baseline to Week 12 will be assessed using laboratory testing.","timeFrame":"Baseline, Week 12"},{"measure":"Change in High-Density Lipoprotein Cholesterol","description":"Change in high-density lipoprotein cholesterol (HDL-C) from baseline to Week 12 will be assessed using laboratory testing.","timeFrame":"Baseline, Week 12"},{"measure":"Change in Low-Density Lipoprotein Cholesterol","description":"Change in low-density lipoprotein cholesterol (LDL-C) from baseline to Week 12 will be assessed using laboratory testing.","timeFrame":"Baseline, Week 12"},{"measure":"Change in Triglycerides","description":"Change in triglycerides from baseline to Week 12 will be assessed using laboratory testing.","timeFrame":"Baseline, Week 12"},{"measure":"Change in Controlled Attenuation Parameter","description":"Change in controlled attenuation parameter (CAP) from baseline to Week 12 will be assessed using transient elastography.","timeFrame":"Baseline, Week 12"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07619989"},{"nctId":"NCT07673900","title":"Semaglutide Delivered Epi-Intradermally by Microarray Patch (VX-201) Versus Subcutaneous Administration in Healthy Overweight and Obese Participants","officialTitle":"A Randomized, Phase 1 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Epi/Intra-dermally Administered Semaglutide (VX-201) Compared to Subcutaneous Administration in Healthy Overweight and Obese Participants: Single and Multiple Dose Assessment","summary":"VX-201-101 is a first-in-human Phase 1 clinical study evaluating VX-201, a needle-free microneedle (MN) array patch (MAP) that delivers semaglutide through the skin as an alternative to subcutaneous (SC) injection.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Overweight and/or Obesity"],"keywords":["first in human","Phase 1","randomized","single ascending dose","multiple dose","open label","pharmacokinetics","microarray patch","semaglutide"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Terrestrial Bio, Inc.","slug":"terrestrial-bio-inc","class":"INDUSTRY"},"collaborators":[{"name":"Celerion","slug":"celerion","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":62,"dates":{"start":"2026-06-15","primaryCompletion":"2027-02-10","completion":"2027-05-18","firstPosted":"2026-06-29","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Celerion Clinical Research","status":"RECRUITING","city":"Tempe","state":"Arizona","country":"United States","latitude":33.41477,"longitude":-111.90931}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* To be eligible for study participation, all subjects must meet all the following inclusion criteria:\n\n  1. Medically healthy with no clinically significant medical history, vital sign, or coagulation results at Screening; chemistry, hematology, or urinalysis at Screening and Day -1 (SAD)/Day 0 (MD) as deemed by the Investigator\n  2. Age 18 to 60 years, inclusive, at the time of Screening\n  3. Body mass index ≥25 to \\<35 kg/m2 if participating in the SAD phase or ≥27 to \\<40 kg/m2 if participating in the MD phase, at the time of Screening\n  4. Must be able to communicate well with the Investigator, understand and comply with the requirements of the study (including required confinement periods), and understand and provide written consent\n\nExclusion Criteria:\n\nAll subjects meeting any of the following criteria will be excluded from this study:\n\n1. Any disorder which in the investigator's opinion might jeopardize the subject's safety, evaluation of results, or compliance with the protocol\n2. Any of the following obesity or glycemia-related history:\n\n   1. Treatment with a GLP-1 receptor agonist within 90 days before screening\n   2. Treatment with any medication for the indication of obesity within the past 90 days before screening\n   3. A self-reported change in body weight \\> 5 kg (11 lb) within 90 days before screening irrespective of medical records.\n   4. Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device\n   5. HbA1c ≥ 6.5% as measured at screening\n   6. History of type 1 or type 2 diabetes mellitus\n3. Have a history of heart block, or a pulse rate (PR) interval \\>200 milliseconds (msec), or any abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study\n4. Have a significant history of or current cardiovascular (myocardial infarction, congestive heart failure, cerebrovascular accident, venous thromboembolism, etc.), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological (including history of thrombocytopenia), or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, or of constituting a risk when taking the study medication, or interfering with the interpretation of data\n5. Estimated glomerular filtration rate \\<80 mL/min as determined by the Mosteller body surface area correction equation at Screening\n6. Have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2\n7. Presence of acute pancreatitis within the past 90 days prior to the day of screening or history or presence of chronic pancreatitis\n8. Active malignancy or history of malignancy of any organ system (other than localized squamous cell or basal cell carcinoma of the skin that have been excised or resolved), treated or untreated, within the past 5 years\n9. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method\n10. Any prescription medications (except for hormonal contraception associated with inhibition of ovulation as described Exclusion 9) within 14 days of Screening\n11. Previously participated in another dose level group in the study\n12. Known hypersensitivity to semaglutide\n13. Known or suspected alcohol or drugs/chemical substance abuse within one year prior to the day of screening, or positive drug or alcohol screen results at Screening or Day-1\n14. Positive result for human immunodeficiency virus (HIV) or presence of actively replicating viral hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at Screening\n15. Excessive tattoos, skin blemishes, or excessive hair near patch administration site\n16. Participation in any clinical study with an investigational or approved drug/device within 30 days or 5 half-lives (whichever is longer) before Screening or is planning to participate in another clinical study while enrolled in this study\n17. Donated or lost \\>200 mL of blood within 60 days before Day -1, donated plasma within 7 days before Day -1, or plans to donate blood or plasma during the study\n18. Is directly affiliated with the study at the study site or is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the study site, or is employed by Terrestrial Bio (that is an employee, temporary contract worker, or designee responsible for the conduct of the study) or is an immediate family member of an employee of Terrestrial Bio","minimumAge":"18 Years","maximumAge":"60 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"COMBINATION_PRODUCT","name":"VX-201","description":"VX-201 is a needle free, shelf-stable, microneedle array patch (MAP) for delivery of semaglutide epi/intra-dermally"},{"type":"DRUG","name":"semaglutide SC","description":"Semaglutide is a long acting GLP-1 analogue with low renal clearance and an elimination half-life of approximately 7 days following subcutaneous administration."}],"primaryOutcomes":[{"measure":"Type, incidence, and severity of treatment emergent adverse events (TEAEs), including assessment of application site skin sensitivity, vital signs, electrocardiograms (ECGs), and clinical laboratory results)","description":null,"timeFrame":"From enrollment until approximately 5 weeks after the last dose of study drug"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07673900"},{"nctId":"NCT07733427","title":"Evaluating the Effectiveness of AIT in the Treatment of Pain Related to Pancreatic Cancer","officialTitle":"A Pilot Study Aimed at Evaluating the Effectiveness of AIT in the Treatment of Pain Related to Pancreatic Cancer","summary":"The aim of this clinical trial is to assess the effectiveness of intratracheal analgesia on pain intensity in cancer patients, from the start of treatment up to 3 months. It will also investigate the safety of this technique. The main questions it seeks to answer are as follows:\n\nWhat is the impact on the use of opioid analgesics, and can this be measured? What is the quality of life? What is the quality of sleep, and can this be assessed? How does the patient's weight change? Is the patient satisfied? What is the patient's overall survival?\n\nThe researchers will assess the equivalent daily dose of morphine (mg/day) between enrolment and follow-up visits, as well as the number of patients requiring an escalation of analgesic treatment. Overall quality of life score measured using the ESAS questionnaire between enrolment and follow-up visits; satisfaction assessed using a numerical satisfaction scale (0-10); sleep quality assessed using the ISI questionnaire; and the tolerability and safety of the technique assessed by monitoring adverse events.\n\nEligible participants:\n\nFollowing implantation of the intrathecal pump, participants will have scheduled consultations at day 30, then at 3, 6, 9 and 12 months, with questionnaires to be completed.","detailedDescription":null,"peptideSlugs":["ziconotide"],"peptideNames":["Ziconotide"],"conditions":["Pancreatic Cancer Pain","Intrathecal Analgesic","Intrathecal Administration of the Drug","Pancreatic Carcinoma"],"keywords":[],"conditionGroups":[{"slug":"pain","label":"Pain"}],"sponsor":{"name":"Clinique Bizet","slug":"clinique-bizet","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":40,"dates":{"start":"2026-06","primaryCompletion":"2027-03","completion":"2027-12","firstPosted":"2026-07-29","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":3,"countries":["France"],"locations":[{"facility":"Benkessou","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Bizet Clinic","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Clinique Bizet","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488}],"eligibility":{"criteria":"Inclusion Criteria:\n\nSubject aged over 20 years\n\n* Patient with histologically confirmed pancreatic carcinoma\n* Chronic cancer-related pain that is inadequately controlled by standard treatment or for whom analgesics are contraindicated.\n* EMO \\< 120 mg/day Patients experiencing side effects: sedation, vomiting, constipation, or an allergy to morphine.\n* Signed informed consent\n* Participants affiliated with or eligible for a social security scheme\n* Agree to complete the various study questionnaires\n\nExclusion Criteria:\n\nPatients under the age of 20.\n\n* Contraindications to intratracheal analgesia\n* Acute respiratory infection\n* Uncontrolled coagulation disorder\n* Pregnancy or breastfeeding\n* Unable to comply with medical follow-up for the study.\n* Adults who are legally protected, under guardianship or under a conservatorship","minimumAge":"20 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DEVICE","name":"Intrathecal catheter connected to an implantable pump","description":"Epidural puncture (AL injection), followed by a lumbar puncture and collection of cerebrospinal fluid. Positioning of the catheter behind the spinal cord at the desired metameric level for the pancreas (T5-T7), and positioning of the pump in the flank or buttock."},{"type":"DRUG","name":"Administration of medication, including analgesics, via an intrathecal catheter connected to an implantable pump or via periodic injections","description":"Medications are administered via an intrathecal catheter connected to an implantable pump or via periodic injections; the patient is admitted to hospital with morphine (IV, PO, transdermal) discontinued on entry to the unit (the same applies to methadone). Depending on the condition of the patient's abdominal skin (stoma, multiple injections, etc.) and any foreseeable technical difficulties during MRI scanning (in the left or right lateral positions), the procedure is performed under fluoroscopy, with appropriate antibiotic prophylaxis, under local anaesthesia, epidural anaesthesia and light sedation. Product used, dosage and frequency:\n\nOpioids: μ and δ receptors: Morphine sulphate: 50 mg/ml Ca++ channels: ziconotide: initial dose 0.5 µg/day Sodium channels: 1% ropivacaine As with a patient-controlled analgesia (PCA) system: Continuous infusion + bolus or sequential boluses Patient education on the use of the pump during their hospital stay."}],"primaryOutcomes":[{"measure":"Change in Edmonton Symptom Assessment System (ESAS) - Pain Subscore","description":"Change in pain intensity score measured by the ESAS subscale from baseline to follow-up visits.\n\nUnit of Measure: Score on a scale (0 to 10) Scale Range (Minimum and Maximum Values): 0 to 10\n\nDirection of Scores: Higher scores mean a worse outcome (greater pain intensity).","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"}],"secondaryOutcomes":[{"measure":"Change in Edmonton Symptom Assessment System (ESAS) Overall Quality of Life Score","description":"Change in overall score as measured by the Edmonton Symptom Assessment System (ESAS) from baseline to follow-up visits.\n\nUnit of Measure: Score on a scale (ESAS Score) Scale Range (Minimum and Maximum Values): 0 to 10\n\nDirection of Scores: Higher scores mean a worse outcome (greater pain intensity).","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Proportion of Patients Requiring Pain Treatment Escalation","description":"Number of patients requiring an increase or escalation in pain management treatment during follow-up.\n\nUnit of Measure: Number of participants (or Percentage)","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Change in Daily Morphine Equivalent Dose (MED)","description":"Change in daily opioid dose from baseline to follow-up visits.\n\nUnit of Measure: mg/day","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Change in Sleep Quality Score Insomnia Severity Index (ISI)","description":"Change in insomnia severity measured by the Insomnia Severity Index (ISI) questionnaire from baseline to follow-up visits.\n\nScale Range (Minimum and Maximum Values): 0 to 28 (Derived from summing the 7 individual items, each scored on a 0 to 4 scale evaluating sleep onset, maintenance, early morning awakening, satisfaction, daytime interference, noticeability, and distress)\n\nDirection of Scores: Higher score 4 means a worse outcome (greater insomnia severity and impaired quality of life)\n\nUnit of Measure: Score on a scale (ISI Score)","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Change in Body Weight","description":"Change in body weight from baseline to follow-up visits.\n\nUnit of Measure: Kilograms (kg)","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Patient Satisfaction Clinical Global Impressions Scale (typically either CGI-Severity or CGI-Improvement)","description":"Overall patient satisfaction Clinical Global Impressions (typically either CGI-Severity or CGI-Improvement) rated on a numerical scale.\n\nUnit of Measure: Score on a scale\n\nScale Range (Minimum and Maximum Values): 1 to 7\n\nDirection of Scores: Higher scores mean a worse outcome (e.g., greater illness severity or worsening condition).","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Incidence of Adverse Events Related to Intratracheal Analgesia","description":"Number of participants experiencing at least one adverse event related to the intratracheal analgesia technique.\n\nUnit of Measure: Number of participants","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"},{"measure":"Incidence of Serious Adverse Events (SAEs)","description":"Number of participants experiencing a serious adverse event during the study period.\n\nUnit of Measure: Number of participants","timeFrame":"Telephone call between Week 1 and Week 12, and questionnaires at Day 30, 3 months, 6 months, 9 months and 12 months"}],"publications":[{"pmid":"35183448","citation":"Park J, Park EY, Han SS, Park HM, Lee M, Lee SA, Kim SW, Kim DH, Park SJ. Randomized controlled study comparing the analgesic effects of intravenous patient-controlled analgesia and patient-controlled epidural analgesia after open major surgery for pancreatobiliary cancer. HPB (Oxford). 2022 Aug;24(8):1238-1244. doi: 10.1016/j.hpb.2022.01.013. Epub 2022 Feb 3."},{"pmid":"28025375","citation":"Bruel BM, Burton AW. Intrathecal Therapy for Cancer-Related Pain. Pain Med. 2016 Dec;17(12):2404-2421. doi: 10.1093/pm/pnw060. Epub 2016 Apr 28."},{"pmid":"18054150","citation":"Cohen SP, Dragovich A. Intrathecal analgesia. Anesthesiol Clin. 2007 Dec;25(4):863-82, viii. doi: 10.1016/j.anclin.2007.07.001."},{"pmid":"18443642","citation":"Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H. Intrathecal drug delivery. Pain Physician. 2008 Mar;11(2 Suppl):S89-S104."},{"pmid":"25638694","citation":"Rizvi S, Kumar K. History and present state of targeted intrathecal drug delivery. Curr Pain Headache Rep. 2015;19(2):474. doi: 10.1007/s11916-014-0474-8."},{"pmid":"10642496","citation":"Haan S, Kortylewski M, Behrmann I, Muller-Esterl W, Heinrich PC, Schaper F. Cytoplasmic STAT proteins associate prior to activation. Biochem J. 2000 Feb 1;345 Pt 3(Pt 3):417-21."},{"pmid":"29543644","citation":"Carvajal G, Dupoiron D, Seegers V, Lebrec N, Bore F, Dubois PY, Leblanc D, Delorme T, Jubier-Hamon S. Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-up Study Over an 11-Year Period in a Comprehensive Cancer Center. Anesth Analg. 2018 Jun;126(6):2038-2046. doi: 10.1213/ANE.0000000000002903."},{"pmid":"14612485","citation":"Bruera E, Kim HN. Cancer pain. JAMA. 2003 Nov 12;290(18):2476-9. doi: 10.1001/jama.290.18.2476. No abstract available."},{"pmid":"10488677","citation":"Caraceni A, Portenoy RK; a working group of the IASP Task Force on Cancer Pain. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. Pain. 1999 Sep;82(3):263-274. doi: 10.1016/S0304-3959(99)00073-1."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07733427"},{"nctId":"NCT07738276","title":"Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity","officialTitle":"Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity: A Double-Blinded Randomized Controlled Trial","summary":"The goal of this clinical trial is to learn if tirzepatide works to improve physical function in adults with heart failure and obesity. It will also learn about the safety of tirzepatide. The main questions it aims to answer are:\n\nDoes tirzepatide improve how far participants can walk in 6 minutes? Does tirzepatide improve heart failure symptoms and quality of life? What side effects do participants have when taking tirzepatide?\n\nResearchers will compare tirzepatide to a placebo (a look-alike substance that contains no drug) to see if tirzepatide improves physical function in people with heart failure and obesity.\n\nParticipants will:\n\nGet a weekly injection of tirzepatide or a placebo under the skin for 6 months Start at a low dose, which may be raised slowly based on how well they tolerate it Keep taking their usual heart failure medicines Visit the clinic for checkups, blood tests, heart ultrasounds, and a 6-minute walk test Answer questions about their quality of life and heart failure symptoms","detailedDescription":"This is a phase 3, randomized, double-blind (participant, care provider, investigator, and outcomes assessor blinded), placebo-controlled, parallel- group clinical trial evaluating the efficacy and safety of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, in participants with heart failure with reduced ejection fraction (HFrEF) and obesity.\n\nEligible participants are adults aged 18 years or older with HFrEF (left ventricular ejection fraction ≤40% on echocardiography within the prior 3 months), a body mass index ≥27 kg/m² with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia), and stable guideline-directed heart failure therapy for at least 4 weeks prior to enrollment. Key exclusion criteria include recent acute heart failure decompensation or hospitalization, uncontrolled blood pressure, advanced kidney disease (eGFR \\<30 mL/min/1.73m²), significant hepatic impairment, active pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, and pregnancy or breastfeeding.\n\nA total of 60 participants will be randomized 1:1 using a computer-generated block randomization schedule (block size of 4) to receive either tirzepatide or matching placebo, both administered as weekly subcutaneous injections. Study drug is initiated at 2.5 mg once weekly and titrated every 4 weeks, as tolerated, up to a maximum of 10 mg once weekly, continuing through month 6. The placebo pen is identical in appearance, packaging, and dosing schedule to maintain blinding.\n\nThe primary outcome is change in 6-minute walk distance from baseline to 6 months. Secondary outcomes include change in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire quality-of-life score, body mass index, ejection fraction, pulmonary artery pressure, and metabolic parameters (fasting glucose, glycated hemoglobin, lipid panel), measured at baseline and at months 2, 4, and 6. Safety outcomes include gastrointestinal adverse events, injection-site reactions, hypoglycemia, pancreatitis, gallbladder events, and changes in liver enzymes, amylase, and lipase. An exploratory outcome evaluates shared molecular and genetic pathways linking obesity and HFrEF using peripheral blood RNA analysis via quantitative PCR or next-generation sequencing.\n\nThe study is being conducted at seven sites in Tehran, Iran, including Masih Daneshvari Hospital, Shahid Rajaei Cardiovascular Medical and Research Center, Rasoul Akram Hospital, Tehran Heart Center, Firoozgar Hospital, Ayatollah Taleghani Hospital, and Imam Khomeini Hospital Complex.","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Heart Failure and Reduced Ejection Fraction","Obesity & Overweight","Tirzepatide"],"keywords":["Tirzepatide","GLP-1/GIP receptor agonist","Heart failure with reduced ejection fraction","Obesity","6-minute walk test","Weight loss","Functional capacity","Randomized controlled trial"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Shahid Beheshti University of Medical Sciences","slug":"shahid-beheshti-university-of-medical-sciences","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":60,"dates":{"start":"2026-07-18","primaryCompletion":"2027-06-11","completion":"2027-12-22","firstPosted":"2026-07-31","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 18 years or older\n* Heart failure with reduced ejection fraction, defined as left ventricular ejection fraction ≤40% on echocardiography performed within the prior 3 months\n* Body mass index ≥27 kg/m², with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia)\n* Stable heart failure therapy for at least 4 weeks prior to enrollment, including beta-blockers, renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors, if prescribed\n* Written informed consent\n\nExclusion Criteria:\n\n* Acute heart failure decompensation or cardiac hospitalization within the prior 4 weeks\n* Uncontrolled blood pressure (systolic blood pressure \\<90 mmHg or ≥180 mmHg)\n* Advanced renal impairment (estimated glomerular filtration rate \\<30 mL/min/1.73m²)\n* Severe hepatic impairment (liver enzymes elevated to 3 times the upper limit of normal)\n* Active pancreatitis\n* Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2\n* Pregnancy or breastfeeding\n* Known hypersensitivity to glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonist drugs\n* Concurrent use of other weight-loss medications","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"dual GLP-1/GIP receptor agonist administered subcutaneously; brief dosing summary"},{"type":"DRUG","name":"Placebo","description":"Matching placebo pen containing all inactive ingredients except tirzepatide"}],"primaryOutcomes":[{"measure":"Change in 6-Minute Walk Distance","description":"The 6-minute walk test will be performed according to the American Thoracic Society standard guidelines in a straight 30-meter corridor. Participants will be asked to walk as far as possible in 6 minutes at their own pace, with rest breaks permitted if needed. Total distance walked will be recorded in meters. This is a standardized, validated, and reproducible tool for assessing functional capacity and exercise tolerance in patients with heart failure.","timeFrame":"Baseline and 6 months after intervention start"}],"secondaryOutcomes":[{"measure":"NYHA Functional Class","description":"Heart failure severity classified according to the New York Heart Association (NYHA) functional classification system.","timeFrame":"Baseline and 6 months after intervention start"},{"measure":"Glycated Hemoglobin (HbA1c)","description":"Measured using standard biochemical assay kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"Fasting Blood Glucose","description":"Venous blood sample collected after at least 8 hours of fasting; fasting glucose measured using standard enzymatic glucose oxidase laboratory kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"Body Mass Index (BMI)","description":"Calculated as weight in kilograms divided by height in meters squared, using standardized stadiometer and scale.","timeFrame":"Baseline and 6 months after intervention start"},{"measure":"Quality of Life (QoL)","description":"Assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.","timeFrame":"Baseline and 6 months after intervention start"},{"measure":"Systolic Blood Pressure","description":"Measured using a calibrated automatic blood pressure device after at least 5 minutes of rest in a seated position.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"Serum Amylase","description":"Venous blood sample; serum amylase measured using standard colorimetric enzymatic laboratory kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"Alanine Aminotransferase (ALT)","description":"Venous blood sample; serum ALT measured using standard enzymatic spectrophotometric laboratory kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)","description":"Measured using human NT-proBNP ELISA kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"},{"measure":"Total Cholesterol","description":"Venous blood sample collected after at least 8 hours of fasting; total cholesterol measured using standard colorimetric enzymatic laboratory kit.","timeFrame":"Baseline, end of month 2, end of month 4, and end of month 6"}],"publications":[{"pmid":"3283935","citation":"Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622-30. doi: 10.1126/science.3283935."},{"pmid":"18193044","citation":"Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS, Wahlstrand B, Hedner T, Corella D, Tai ES, Ordovas JM, Berglund G, Vartiainen E, Jousilahti P, Hedblad B, Taskinen MR, Newton-Cheh C, Salomaa V, Peltonen L, Groop L, Altshuler DM, Orho-Melander M. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008 Feb;40(2):189-97. doi: 10.1038/ng.75. Epub 2008 Jan 13."},{"pmid":"18159244","citation":"Hinney A, Nguyen TT, Scherag A, Friedel S, Bronner G, Muller TD, Grallert H, Illig T, Wichmann HE, Rief W, Schafer H, Hebebrand J. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One. 2007 Dec 26;2(12):e1361. doi: 10.1371/journal.pone.0001361."},{"pmid":"34811547","citation":"Klarin D, Natarajan P. Clinical utility of polygenic risk scores for coronary artery disease. Nat Rev Cardiol. 2022 May;19(5):291-301. doi: 10.1038/s41569-021-00638-w. Epub 2021 Nov 22."},{"pmid":"38632048","citation":"Wallner M, Biber ME, Stolfo D, Sinagra G, Benson L, Dahlstrom U, Gudbjornsdottir S, Cosentino F, Mol PGM, Rosano GMC, Butler J, Metra M, Lund LH, Ferrannini G, Savarese G. Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries. Eur Heart J Cardiovasc Pharmacother. 2024 Jul 16;10(4):296-306. doi: 10.1093/ehjcvp/pvae026."},{"pmid":"37932236","citation":"Hankosky ER, Wang H, Neff LM, Kan H, Wang F, Ahmad NN, Griffin R, Stefanski A, Garvey WT. Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis. Diabetes Obes Metab. 2024 Jan;26(1):319-328. doi: 10.1111/dom.15318. Epub 2023 Nov 6."},{"pmid":"39551891","citation":"Borlaug BA, Zile MR, Kramer CM, Baum SJ, Hurt K, Litwin SE, Murakami M, Ou Y, Upadhyay N, Packer M. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med. 2025 Feb;31(2):544-551. doi: 10.1038/s41591-024-03374-z. Epub 2024 Nov 17."},{"pmid":"39556714","citation":"Zile MR, Borlaug BA, Kramer CM, Baum SJ, Litwin SE, Menon V, Ou Y, Weerakkody GJ, Hurt KC, Kanu C, Murakami M, Packer M; SUMMIT Trial Study Group. Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity. Circulation. 2025 Mar 11;151(10):656-668. doi: 10.1161/CIRCULATIONAHA.124.072679. Epub 2024 Nov 18."},{"pmid":"39555826","citation":"Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, Weerakkody GJ, Ou Y, Bunck MC, Hurt KC, Murakami M, Borlaug BA; SUMMIT Trial Study Group. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025 Jan 30;392(5):427-437. doi: 10.1056/NEJMoa2410027. Epub 2024 Nov 16."},{"pmid":"37952180","citation":"Kosiborod MN, Verma S, Borlaug BA, Butler J, Davies MJ, Jon Jensen T, Rasmussen S, Erlang Marstrand P, Petrie MC, Shah SJ, Ito H, Schou M, Melenovsky V, Abhayaratna W, Kitzman DW; STEP-HFpEF Trial Committees and Investigators. Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial. Circulation. 2024 Jan 16;149(3):204-216. doi: 10.1161/CIRCULATIONAHA.123.067505. Epub 2023 Nov 12."},{"pmid":"38819334","citation":"Petrie MC, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, Verma S, Jensen TJ, Einfeldt MN, Liisberg K, Perna E, Sharma K, Ezekowitz JA, Fu M, Melenovsky V, Ito H, Lelonek M, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program. J Am Coll Cardiol. 2024 Jul 2;84(1):27-40. doi: 10.1016/j.jacc.2024.04.022. Epub 2024 May 13."},{"pmid":"37622681","citation":"Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963. Epub 2023 Aug 25."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07738276"},{"nctId":"NCT07738614","title":"A Study of Eloralintide (LY3841136) in Participants With Obesity or Overweight","officialTitle":"A Phase 1, Investigator- and Participant-Blinded, Placebo-Controlled, Randomized, Multiple-Dose Study to Evaluate the Gastric Emptying Delay, Pharmacokinetics, Safety, and Tolerability of Eloralintide in Participants With Obesity or Overweight","summary":"The main purpose of this study is to find out how significantly Eloralintide slows stomach emptying in participants who are overweight or obese. For each participant, the study will last approximately 21 weeks and will include 2 overnight stays in the clinical research unit (CRU) lasting between 4 and 8 days. There will be 13 other visits.","detailedDescription":null,"peptideSlugs":["eloralintide"],"peptideNames":["Eloralintide"],"conditions":["Obesity","Overweight"],"keywords":["Healthy"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":56,"dates":{"start":"2026-07","primaryCompletion":"2026-12","completion":"2026-12","firstPosted":"2026-07-31","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":2,"countries":["Singapore","United States"],"locations":[{"facility":"ICON Early Phase Services","status":null,"city":"San Antonio","state":"Texas","country":"United States","latitude":29.42412,"longitude":-98.49363},{"facility":"Lilly Centre for Clinical Pharmacology","status":null,"city":"Singapore","state":null,"country":"Singapore","latitude":1.28967,"longitude":103.85007}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Have overweight or obesity, but are otherwise overtly healthy.\n* Have a body mass index (BMI) within the range of 27.0 to 45.0 kilograms (kg)/square meter (m²), inclusive.\n* Have had a stable body weight, with less than 5 percent (%) change during the 3-month period prior to screening.\n\nExclusion Criteria:\n\n* Have been diagnosed with Type 1 or Type 2 diabetes mellitus, or have either of the following at screening\n\n  * A fasting plasma glucose concentration greater than or equal to 126 milligrams (mg)/deciliter (dL) or 7.0 millimoles (mmol)/liter (L), or\n  * Hemoglobin A1C (HbA1c) greater than or equal to 6.5% or 48 mmol/mole (mol).\n* Have a history or presence of psychiatric disorders, including a history of major depressive disorder or severe psychiatric disorders such as schizophrenia, and bipolar disorder, within the last 2 years.\n* Have received a glucagon-like peptide-1 (GLP-1) receptor agonist, glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, or GIP/GLP-1/glucagon receptor agonist within 60 days or 5 half-lives, whichever is longer, prior to screening.\n* Are in the judgment of the investigator, actively suicidal or deemed to be at significant risk for suicide.","minimumAge":"18 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Eloralintide","description":"Administered SC"},{"type":"DRUG","name":"Placebo","description":"Administered SC"},{"type":"DRUG","name":"Acetaminophen","description":"Administered Oral Solution"}],"primaryOutcomes":[{"measure":"Acetaminophen Area Under the Concentration Versus Time Curve (AUC)","description":null,"timeFrame":"Baseline to Day 65"},{"measure":"Acetaminophen Maximum Observed Concentration (Cₘₐₓ)","description":null,"timeFrame":"Baseline to Day 65"},{"measure":"Acetaminophen Time to Maximum Observed Drug Concentration (tₘₐₓ)","description":null,"timeFrame":"Baseline to Day 65"}],"secondaryOutcomes":[{"measure":"Eloralintide AUC","description":null,"timeFrame":"Baseline to Day 106"},{"measure":"Eloralintide Cₘₐₓ","description":null,"timeFrame":"Baseline to Day 106"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07738614"},{"nctId":"NCT07740291","title":"Tirzepatide Impact Assessment Study","officialTitle":"Tirzepatide Impact Assessment: Exploring Health and Wellness Outcomes","summary":"This study examines how two different weight-loss strategies affect heart and metabolic health, as well as changes at the molecular level in the body. One group includes adults who are starting a GLP-1 receptor agonist medication (i.e., semaglutide or tirzepatide) prescribed by their own doctor for weight loss. The other group includes adults who will participate in a structured lifestyle program combining a reduced-calorie diet with increased physical activity. Both groups complete assessments at the start of the study and again after three months.\n\nAt each visit, participants have their weight, body composition, blood pressure, and resting metabolic rate measured. A blood draw is collected to evaluate cholesterol, blood sugar, insulin, appetite hormones, and liver and kidney function markers, and to analyze gene activity (RNA sequencing) and metabolites, which are small molecules that reflect how the body is using energy and nutrients. Participants also complete online questionnaires about diet, disordered eating, stress, mental health, and quality of life. Those in the lifestyle group attend three individual nutrition and physical activity counseling sessions over the course of the study.\n\nThe main goals of the study are (1) to determine whether GLP-1 receptor agonist medication or lifestyle changes produce greater improvements in heart and metabolic health markers over three months; (2) to examine if GLP-1 receptor agonist medication or lifestyle changes produce greater improvement in disordered eating, stress, mental health, and quality of life; (3) to investigate if GLP-1 receptor agonist medication or lifestyle changes produce greater improvement in appetite-related hormones (i.e., ghrelin, GLP-1, insulin, leptin, and peptide YY); and (4) to explore whether the two approaches cause different changes in gene expression and metabolic profiles. This is a pilot study conducted at Texas Tech University's Nutrition and Metabolic Health Initiative clinic in Lubbock, Texas.\n\nWho can participate: Adults aged 18 years and older with a BMI of 27.5 or higher who are either starting semaglutide or tirzepatide therapy for weight management or who are seeking weight management without the use of weight-loss medications.\n\nWho cannot participate: Individuals who are pregnant or lactating, have a pacemaker or internal medical device, have certain serious medical conditions (such as active cancer, uncontrolled hypertension, or severe kidney disease), have type 1 diabetes, or use insulin for type 2 diabetes.","detailedDescription":"This prospective non-randomized comparative pilot study is conducted at the Nutrition and Metabolic Health Initiative (NMHI) clinic at Texas Tech University in Lubbock, Texas. The study includes two arms: a GLP-1 receptor agonist (GLP-1 RA) arm and a lifestyle (LS) comparator arm. GLP-1 RA arm participants are recruited from obesity medicine and aesthetics clinics in Lubbock, Texas, and enrolled within 0 to 3 days of initiating semaglutide or tirzepatide as prescribed by their own medical provider. LS comparator arm participants are recruited from the community via flyers, community events, hospital intranet postings, and university listservs; they will receive a structured behavioral intervention at no cost.\n\nEach arm follows a two-visit assessment schedule at baseline and at three months. In-person visits include anthropometric measurement, bioelectrical impedance analysis for body composition, resting metabolic rate assessment via MedGem indirect calorimetry, blood pressure measurement (average of two readings after a five-minute rest), and venipuncture for biological sample collection. Blood is drawn into serum-separating tubes and an EDTA tube. Serum is processed for lipid panels, basal metabolic panels, hepatic and renal function markers including alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine, as well as appetite-related hormones including ghrelin, GLP-1, insulin, leptin, and peptide YY. The EDTA tube is processed for whole-blood RNA sequencing and untargeted metabolomics. Participants also wear a Garmin device for two weeks following the baseline visit to monitor sleep, heart rate, and oxygen saturation. Online questionnaires are completed via Qualtrics prior to each in-person visit.\n\nLS comparator participants receive three individual lifestyle education sessions across the study period: at baseline, at one month, and at two months. Sessions may be completed in person or via a HIPAA-secured video platform and last approximately 30 to 45 minutes each. Each participant's total energy expenditure (TEE) is estimated by multiplying measured resting metabolic rate by a physical activity factor. Participants are instructed to follow a 500 kilocalorie daily deficit from TEE and to accumulate 150 to 300 minutes of moderate-intensity physical activity per week. Meal plans are based on the Academy of Nutrition and Dietetics Nutrition Care Manual. Dietary and physical activity adherence is monitored using MyFitnessPal or a food journal, with records reviewed at each session.\n\nGiven the pilot nature of this study, the primary emphasis is on effect size estimation and variance characterization to inform future adequately powered trials rather than definitive hypothesis testing. For example, with 12 participants in the GLP-1 receptor agonist arm and 15 participants in the LS comparator arm, the study is powered to detect only large between-group differences in cardiometabolic outcomes. Transcriptomic and metabolomic findings should be interpreted as hypothesis-generating. IRB approval was obtained prior to study initiation (IRB Number: IRB2024-370).","peptideSlugs":["tirzepatide","semaglutide"],"peptideNames":["Tirzepatide","Semaglutide"],"conditions":["Obesity & Overweight","Cardiometabolic Health Indicators","Addiction","Eating Disorders","Mental Health"],"keywords":["GLP-1 receptor agonists","obesity","Multi-omics profiling","Semaglutide","Tirzepatide","Appetite Regulation","Addictive Behaviors","eating disorders","appetite-related hormones","mental health"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Texas Tech University","slug":"texas-tech-university","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":27,"dates":{"start":"2025-01-02","primaryCompletion":"2026-11-23","completion":"2026-12-07","firstPosted":"2026-07-31","resultsPosted":null,"lastUpdated":"2026-07-31"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Nutrition Metabolic Health Initiative (NMHI)","status":"RECRUITING","city":"Lubbock","state":"Texas","country":"United States","latitude":33.57786,"longitude":-101.85517}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 18 years or older\n* BMI of 27.5 kg/m2 or higher\n* For GLP-1 RA arm: initiating semaglutide or tirzepatide for weight loss as prescribed by their own medical provider\n* For LS comparator arm: not currently taking a GLP-1 receptor agonist or other weight-loss medication, and no use of weight-loss medication within the past 3 months\n\nExclusion Criteria:\n\n* Pregnant\n* Breastfeeding\n* Wears a pacemaker or other internal medical device\n* Chronic kidney disease in the past 2 years\n* Active cancer or cancer treatment within the past 6 months\n* Current diagnosis of any major endocrine, inflammatory, cardiovascular, or neurological disorder/condition, including Addison's disease, autism, congestive heart failure, Crohn's disease, Cushing's syndrome, hyperparathyroidism, multiple sclerosis, neuromuscular disorders (Guillain-Barre syndrome or myasthenia gravis), stroke, thyroid gland disorders (hyperthyroidism or hypothyroidism), type 1 diabetes, and ulcerative colitis\n* Insulin therapy for type 2 diabetes\n* For LS comparator arm only: initiating any weight-loss medication (including a GLP-1 receptor agonist) currently or within the past 3 months","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"GLP-1 Receptor Agonist Therapy","description":"Participants receive semaglutide or tirzepatide as prescribed by their own medical provider prior to study enrollment. Dosing and titration followed the prescribing provider's clinical judgment and are not controlled by the study team. Both medications are GLP-1 receptor agonists approved for weight management and glycemic control; tirzepatide additionally acts on the glucose-dependent insulinotropic polypeptide (GIP) receptor."},{"type":"BEHAVIORAL","name":"Structured Lifestyle Intervention","description":"A reduced-calorie diet providing a 500 kcal daily deficit from individually calculated total energy expenditure, combined with a goal of 150 to 300 minutes of moderate-intensity physical activity per week. Total energy expenditure is estimated by multiplying each participant's measured resting metabolic rate (MedGem indirect calorimetry) by a standard physical activity factor. Meal plans are based on the Academy of Nutrition and Dietetics Nutrition Care Manual. Three individual counseling sessions are delivered over three months in person or via a HIPAA-secured video platform."}],"primaryOutcomes":[{"measure":"Change in Fasting Blood Glucose","description":"Fasting serum blood glucose measured from venipuncture sample and analyzed as part of the basal metabolic panel. Used as the reference outcome for power estimation; a between-group difference of 4.71 mg/dL was the minimum detectable effect based on a prior semaglutide meta-analysis (SD = 9.9 mg/dL).","timeFrame":"Baseline and 3 months"},{"measure":"Change in LDL Cholesterol","description":"Serum LDL cholesterol measured from a fasting venipuncture sample. A decrease of 10% or more from baseline is considered clinically meaningful.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Triglycerides","description":"Serum triglycerides measured from fasting venipuncture sample. A decrease of 30% or more from baseline is considered clinically meaningful.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Fasting Insulin","description":"Serum fasting insulin measured from venipuncture sample. Used alongside fasting glucose to characterize insulin resistance.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Blood Pressure","description":"Systolic and diastolic blood pressure measured using a digital monitor after a five-minute rest period. The average of two readings taken five minutes apart is recorded.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Disordered Eating","description":"Disordered eating characteristics including dietary restraint, eating concern, shape concern, and weight concern assessed using the Eating Disorder Examination Questionnaire (EDE-Q) administered via Qualtrics.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Food Addiction","description":"Food addiction symptom count and severity assessed using the Modified Yale Food Addiction Scale Version 2.0 (mYFAS 2.0) administered via Qualtrics.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Alcohol Use","description":"Alcohol use frequency, quantity, and disorder risk assessed using the Alcohol Use Disorders Identification Test (AUDIT) and a 30-day frequency and quantity measure administered via Qualtrics.","timeFrame":"Time Frame: Baseline and 3 months"}],"secondaryOutcomes":[{"measure":"Differential Gene Expression Profiles","description":"Whole-blood RNA sequencing analyzed using DESeq2 to identify differentially expressed genes from baseline to 3 months within each arm and between arms. Gene Set Enrichment Analysis used to identify enriched biological pathways.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Plasma Metabolomic Signatures","description":"Untargeted metabolomics conducted on plasma samples. Univariate and multivariate analyses including principal component analysis and partial least squares discriminant analysis performed using the MetaboAnalyst R package.","timeFrame":"Baseline and 3 months"},{"measure":"Association Between Gene Expression Changes and Cardiometabolic Outcome Changes","description":"Pearson or Spearman correlations and partial least squares regression used to examine associations between transcriptomic change scores and changes in lipid panel, blood glucose, insulin, and blood pressure within and between arms.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Dietary Intake","description":"Dietary intake patterns assessed using the Short Food Frequency Questionnaire administered via Qualtrics.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Physical Activity","description":"Self-reported physical activity level assessed using the Rapid Assessment of Physical Activity (RAPA) questionnaire administered via Qualtrics, with objective daily step count additionally tracked via Garmin Vivofit4 watch throughout the 3-month study period.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Sleep Duration","description":"Nightly sleep duration tracked continuously via Garmin Vivofit4 watch, with participants syncing device data to the Garmin app at least weekly throughout the 3-month study period.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Health-Related Quality of Life","description":"General health-related quality of life assessed using the WHO Health-Related Quality of Life (HRQOL) measure and gastrointestinal quality of life assessed using the Gastrointestinal Quality of Life questionnaire, both administered via Qualtrics.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Liver Enzymes","description":"Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measured from a fasting venipuncture sample as indicators of hepatic function.","timeFrame":"Baseline and 3 months"},{"measure":"Change in Renal and Hepatic Markers","description":"Serum total bilirubin and creatinine measured from a fasting venipuncture sample as indicators of hepatic and renal function.","timeFrame":"Baseline and 3 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07740291"},{"nctId":"NCT05567198","title":"Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires","officialTitle":"Efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires","summary":"Background:\n\nSystemic lupus erythematosus (SLE) is a disease that affects females nine times more often than males. People with SLE are often treated with cyclophosphamide (CYC). But CYC can damage a woman s ovaries; it may cause infertility. A drug called GnRHa is sometimes given to protect the ovaries during CYC therapy. But no one really knows how effective GnRHa treatment is. This natural history survey will compare women who received GnRHa during CYC therapy with those who did not.\n\nObjective:\n\nTo find out whether GnRHa can help protect women s ovaries during CYC.\n\nEligibility:\n\nWomen under age 40 years starting CYC treatment with or without GnRHa.\n\nDesign:\n\nThis study will do 2 things: It will conduct patient surveys. It will collect data from medical records.\n\nParticipants will complete a one-time survey. They will answer questions about their menstrual cycle. They will be asked about their history of pregnancy or infertility.\n\nParticipants can take the survey in 4 ways:\n\nOn paper, sent through the mail.\n\nOnline, in a secure web page managed by the NIH.\n\nBy phone.\n\nIn person, during a routine visit to the NIH clinic.\n\nThe survey will take about 30 minutes.\n\nParticipants medical records will be reviewed. Researchers will look for data about the participants SLE disease. This may include their symptoms and the results of their blood tests. It may also include the details of prior treatments.\n\nResearchers will also collect data about participants reproductive history. This may include their personal or family history of infertility. It may include any fertility treatments and any sexually transmitted infections.\n\n...","detailedDescription":"Study Description: SLE patients with life-threatening lupus manifestations are often treated with cyclophosphamide (CYC), which has known cytotoxic effects on ovarian reserve. Co-administration of Gonadotropinreleasing hormone agonist (GnRHa) is suggested to protect ovaries from the cytotoxic effects of CYC but there is lack of data to support this. We hypothesize that the co-administration of a GnRH agonist for the duration of CYC therapy will exert protective effects on ovarian reserve and function in SLE females. We plan to do a patient survey and a retrospective data collection to compare ovarian function in subjects who received CYC with GnRHa to those who received CYC without GnRHa.\n\nObjectives:\n\nPrimary Objective: Determine the effectiveness of GnRH-a in preventing primary ovarian insufficiency (POI) in female SLE patients getting cyclophosphamide treatment.\n\nSecondary Objectives: Determine the effects of SLE disease activity, damage accrual, cumulative dose of cyclophosphamide and other demographic and clinical variables in preventing primary ovarian insufficiency.","peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Systemic Lupus Erythematosus (Sle)","Primary Ovarian Insufficiency (Poi)"],"keywords":["Primary Ovarian Insufficiency (Poi)","Nephritis","Neuro-Psychiatric Lupus","Anti-Mullerian Hormone (Amh)","Natural History"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","slug":"national-institute-of-arthritis-and-musculoskeletal-and-skin-diseases-niams","class":"NIH"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":100,"dates":{"start":"2023-03-03","primaryCompletion":"2027-05-31","completion":"2027-05-31","firstPosted":"2022-10-05","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","status":"RECRUITING","city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026}],"eligibility":{"criteria":"* ELIGIBILITY CRITERIA:\n* INCLUSION CRITERIA: Group 1: SLE patients receiving CYC alone\n\nSLE females \\<40 years at the beginning of CYC treatment without GnRH-a cotreatment.\n\n-EXCLUSION CRITERIA: Group 1: SLE patients receiving CYC alone\n\nFemales \\>40 years at the beginning of CYC treatment; any females with a prior history of reproductive disorders, infertility, or untreated sexually transmitted infections (STIs).\n\n-INCLUSION CRITERIA: Group 2: SLE patients receiving both CYC and leuprolide acetate (GnRH-a). Leuprolide acetate was injected at a dose of either 3.75 mg/month or 11.25mg/every 3 months.\n\nSLE females \\<40 years at the beginning of CYC treatment with GnRH-a cotreatment.\n\n-EXCLUSION CRITERIA: Group 2: SLE patients receiving both CYC and leuprolide acetate (GnRH-a). Leuprolide acetate was injected at a dose of either 3.75 mg/month or 11.25mg/every 3 months.\n\nFemales \\>40 years at the beginning of CYC treatment; any females with a prior history of reproductive disorders, infertility, or untreated STIs.\n\n-Group: Control subjects.\n\nAge-matched female SLE patients without a history of reproductive disorders, infertility, or untreated STIs, who have not received CYC either with or without GnRH-a.","minimumAge":"18 Years","maximumAge":"120 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[],"primaryOutcomes":[{"measure":"POI","description":"The primary outcome variable is POI, and we want to determine whether GnRH-a coadministration with CYC protects against POI incidence in pre-menopausal SLE females. The age of menopause onset will be collected from previous medical records or survey responses and compared across all three groups. Onset of menopause prior to the age of 40 will be considered POI, whereas menopause onset beyond the age of 40 will be considered natural menopause.","timeFrame":"End of study"}],"secondaryOutcomes":[{"measure":"Record Effects of CYC administration with GnRH-a on menstrual cycle","description":"\\- Menses cycles will be classified as either regular (consistently having a period of normal duration each month) or irregular (frequent, infrequent, or absent periods). Classifications of irregular cycle subcategories will be provided, which include polymenorrhea (frequent periods with a cycle length \\<21 days), oligomenorrhea (infrequent menses with cycle length between 37 to 90 days), or amenorrhea (absence of a period for \\>90 days). - Menopausal signs and symptoms will include vaginal dryness, hot flashes, chills, sleeping disturbances, night sweats, mood changes, weight gain, loss of breast fullness, thinning hair, or dry skin. - Inability to conceive will be defined as 12 months of trying to conceive without success.","timeFrame":"End of study"},{"measure":"SLE disease activity as measured by SELENA-SLEDAI score at the start of CYC treatment","description":"These include SLE disease activity as measured by SELENA-SLEDAI score at the start of CYC treatment, damage index score as measured by SLICC/ACR DI, cumulative CYC dose, and age at the time of beginning CYC.","timeFrame":"End of study"}],"publications":[{"pmid":"7108499","citation":"Friedman RC, Clarkin JF, Corn R, Aronoff MS, Hurt SW, Murphy MC. DSM-III and affective pathology in hospitalized adolescents. J Nerv Ment Dis. 1982 Sep;170(9):511-21. doi: 10.1097/00005053-198209000-00001. No abstract available."},{"pmid":"24081299","citation":"Kiriakidou M, Cotton D, Taichman D, Williams S. Systemic lupus erythematosus. Ann Intern Med. 2013 Oct 1;159(7):ITC4-1. doi: 10.7326/0003-4819-159-7-201310010-01004. No abstract available."},{"pmid":"4555317","citation":"Stamenovic B. [Effect of increased chloride on the spontaneous release of acetylcholine in the neuromuscular synapses of amphibia poisoned with Clostridium toxin Type A]. Vojnosanit Pregl. 1972 Mar;29(3):139-44. No abstract available. Serbian."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05567198"},{"nctId":"NCT05765500","title":"RecoverPC: Relugolix vs GnRH Agonist in Quality of Life","officialTitle":"RecoverPC: A Phase 2 Study of RElugolix Versus GnRH Agonist Quality of Life (QOL) and Testosterone reCOVERy in Men With Prostate Cancer","summary":"This study is testing the way that approved androgen deprivation therapy treatments, Leuprolide and Relugolix, for prostate cancer affect quality of life, blood levels, cholesterol, and blood sugar. The drugs are already standard treatment for people with prostate cancer, and the drugs will be used as described in their label.\n\nThe names of the study drugs involved in this study are:\n\n* Leuprolide (type of ADT)\n* Relugolix (type of ADT)","detailedDescription":"This is a phase 2 clinical trial comparing patient-reported Quality of Life (QOL) among men with localized or biochemically recurrent prostate cancer treated with relugolix versus leuprolide depot therapy.\n\nParticipants will be randomized into one of the study groups leuprolide versus relugolix. Randomization means that a participant is put into a study group by chance.\n\nThe U.S. Food and Drug Administration (FDA) has approved leuprolide and relugolix as treatment options for prostate cancer.\n\nThe research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, ECGs, and blood tests.\n\nParticipation in this research study is expected to last 12 months.\n\nIt is expected about 110 people will take part in this research study.\n\nThe Prostate Cancer Foundation and Pfizer are supporting this research study by providing funding. Myovant is supporting this study by providing the drug, Relugolix.","peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Prostate Cancer","Prostatic Neoplasms"],"keywords":["Prostate Cancer","Prostate Neoplasms"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Dana-Farber Cancer Institute","slug":"dana-farber-cancer-institute","class":"OTHER"},"collaborators":[{"name":"Prostate Cancer Foundation","slug":"prostate-cancer-foundation","class":"OTHER"},{"name":"Pfizer","slug":"pfizer","class":"INDUSTRY"},{"name":"Sumitomo Pharma America, Inc.","slug":"sumitomo-pharma-america-inc","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":110,"dates":{"start":"2024-02-12","primaryCompletion":"2027-07-01","completion":"2028-01-01","firstPosted":"2023-03-13","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":3,"countries":["United States"],"locations":[{"facility":"Brigham and Women's Hospital","status":"NOT_YET_RECRUITING","city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977},{"facility":"Dana-Farber Cancer Institute","status":"RECRUITING","city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977},{"facility":"Dana-Farber Cancer Institute at Foxborough","status":"RECRUITING","city":"Foxborough","state":"Massachusetts","country":"United States","latitude":42.06538,"longitude":-71.24783}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Participants must have a histologic diagnosis of prostate adenocarcinoma.\n* Participants must be eligible for treatment with 6 months of ADT with leuprolide depot or relugolix without additional systemic therapies other than first generation androgen receptor antagonists (eg. bicalutamide, nilutamide, flutamide).\n* Participants cannot have received prior GnRH agonist or antagonist therapy.\n* Patients must have testosterone level \\> 200 ng/mL prior to initiation of ADT.\n* Age ≥18 years.\n* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).\n* Life expectancy of greater than 12 months\n* Participants must have adequate organ and marrow function as defined below:\n\n  * leukocytes ≥3,000/mcL\n  * absolute neutrophil count ≥1,500/mcL\n  * platelets ≥100,000/mcL\n  * total bilirubin ≤ institutional upper limit of normal (ULN) unless known or suspected Gilbert syndrome\n  * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN\n  * creatinine ≤ institutional ULN OR\n  * glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2 (see Appendix B).\n* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.\n* The effects of relugolix and leuprolide on the developing human fetus are unknown. For this reason and because GnRH agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of relugolix or leuprolide depot administration.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* History of major adverse cardiac event, including myocardial infarction, new congestive heart failure (CHF) or CHF exacerbation, or stroke, within the past 6 months.\n* Participants who have prior or planned concurrent treatment with second generation AR targeted therapies (such as abiraterone, enzalutamide, darolutamide, apalutamide).\n* Participants who are receiving any other investigational agents.\n* Patients with brain metastases will be excluded from the study as intermittent hormonal therapy is not standard of care treatment for this population.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to leuprolide depot or relugolix.\n* Participants with uncontrolled intercurrent illness.\n* Participant is unable to swallow pills.","minimumAge":"18 Years","maximumAge":null,"sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Relugolix","description":"Gonadotropin-releasing hormone (GnRH) antagonist, oral tablet taken 1x daily."},{"type":"DRUG","name":"Leuprolide","description":"Gonadotropin-releasing hormone (GnRH) antagonist, intramuscular injection 1x every 3 months."}],"primaryOutcomes":[{"measure":"9-month Quality of Life (QOL) Score","description":"The QOL assessed using Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire, defined protocol section 11.1.1: The FACT-P (version 4) contains 39 Likert-type items distributed over 5 subscales: physical (7 items), social/family (7 items), emotional (6 items), and functional (7 items) well-being, and the additional concerns related to prostate cancer scale (12 items). The FACT-P total score is calculated by summing all these 5 subscales and ranges from 0 to 156.","timeFrame":"At 9 months"}],"secondaryOutcomes":[{"measure":"12-month Quality of Life (QOL) Score","description":"The QOL assessed using Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire, defined protocol section 11.1.1: The FACT-P (version 4) contains 39 Likert-type items distributed over 5 subscales: physical (7 items), social/family (7 items), emotional (6 items), and functional (7 items) well-being, and the additional concerns related to prostate cancer scale (12 items). The FACT-P total score is calculated by summing all these 5 subscales and ranges from 0 to 156.","timeFrame":"At 12 months"},{"measure":"9-month Hot flash related daily interference scale (HFRDIS)","description":"HFRDIS was Self-reported daily hot flash interference will be assessed with the Hot Flash-Related Daily Interference Scale, a valid and reliable measure used in prior prostate cancer studies. This scale assesses the impact of hot flashes on daily activities as well as overall quality of life. Total scores range from 0 - 100; higher scores indicate greater interference.","timeFrame":"At 9 months"},{"measure":"9-month Insomnia Severity Index (ISI) Score","description":"ISI Insomnia symptoms will be assessed using the ISI, which has been used in previous assessments of cancer patients, including men with prostate cancer. This questionnaire has 7 items asking about difficulties falling asleep, staying asleep, problems with waking too early and the satisfaction level with their current sleep pattern. Each item was rated on a scale from 0 to 4, where a higher score indicates a more severe insomnia.","timeFrame":"At 9 months"},{"measure":"9-month Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score","description":"Fatigue symptoms will be assessed with the FACIT-Fatigue survey, a valid and reliable instrument used in prostate cancer and other cancer studies, comprised of 13 items and rated on a 5 point Likert-type scale.","timeFrame":"At 9 months"},{"measure":"9-month EPIC-26 Sexual Function Summary Score","description":"Self-reported sexual function will be assessed using the sexual health section of the EPIC-26.","timeFrame":"At 9 months"},{"measure":"12-month Hot flash related daily interference scale (HFRDIS)","description":"HFRDIS was Self-reported daily hot flash interference will be assessed with the Hot Flash-Related Daily Interference Scale. This scale assesses the impact of hot flashes on daily activities as well as overall quality of life. Total scores range from 0 - 100; higher scores indicate greater interference.","timeFrame":"At 12 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05765500"},{"nctId":"NCT05882045","title":"A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease","officialTitle":"A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease","summary":"The main purpose of this study is to evaluate the efficacy and safety of retatrutide once weekly in participants with obesity and established cardiovascular disease (CVD). The study will last about 113 weeks.","detailedDescription":null,"peptideSlugs":["retatrutide"],"peptideNames":["Retatrutide"],"conditions":["Obesity","Cardiovascular Diseases"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":1946,"dates":{"start":"2023-05-30","primaryCompletion":"2026-04-16","completion":"2026-05-14","firstPosted":"2023-05-31","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":169,"countries":["Argentina","Australia","Canada","Hungary","Mexico","Poland","Puerto Rico","Slovakia","Spain","United States"],"locations":[{"facility":"Central Phoenix Medical Clinic","status":null,"city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Valley Clinical Trials, Inc.","status":null,"city":"Covina","state":"California","country":"United States","latitude":34.09001,"longitude":-117.89034},{"facility":"Neuro-Pain Medical Center","status":null,"city":"Fresno","state":"California","country":"United States","latitude":36.74773,"longitude":-119.77237},{"facility":"Valley Research","status":null,"city":"Fresno","state":"California","country":"United States","latitude":36.74773,"longitude":-119.77237},{"facility":"Collaborative Neuroscience Research, LLC","status":null,"city":"Los Alamitos","state":"California","country":"United States","latitude":33.80307,"longitude":-118.07256},{"facility":"Velocity Clinical Research, Westlake","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Valley Clinical Trials, Inc.","status":null,"city":"Northridge","state":"California","country":"United States","latitude":34.22834,"longitude":-118.53675},{"facility":"Velocity Clinical Research, Panorama City","status":null,"city":"Van Nuys","state":"California","country":"United States","latitude":34.18667,"longitude":-118.44897},{"facility":"Chase Medical Research, LLC","status":null,"city":"Waterbury","state":"Connecticut","country":"United States","latitude":41.55815,"longitude":-73.0515},{"facility":"Indago Research & Health Center, Inc","status":null,"city":"Hialeah","state":"Florida","country":"United States","latitude":25.8576,"longitude":-80.27811},{"facility":"Clinical Neuroscience Solutions, Inc. dba CNS Healthcare","status":null,"city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"Clinical Neuroscience Solutions, Inc.","status":null,"city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Charter Research - Winter Park","status":null,"city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Progressive Medical Research","status":null,"city":"Port Orange","state":"Florida","country":"United States","latitude":29.13832,"longitude":-80.99561},{"facility":"Pacific Diabetes & Endocrine Center","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Elite Clinical Trials","status":null,"city":"Blackfoot","state":"Idaho","country":"United States","latitude":43.19047,"longitude":-112.34498},{"facility":"Humphreys Diabetes Center","status":null,"city":"Boise","state":"Idaho","country":"United States","latitude":43.6135,"longitude":-116.20345},{"facility":"Northwestern University","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Great Lakes Clinical Trials - Gurnee","status":null,"city":"Gurnee","state":"Illinois","country":"United States","latitude":42.3703,"longitude":-87.90202},{"facility":"Central Illinois Diabetes and Clinical Research a Division of Prairie Education and Research Cooperative","status":null,"city":"Springfield","state":"Illinois","country":"United States","latitude":39.80172,"longitude":-89.64371},{"facility":"Brengle Family Medicine","status":null,"city":"Indianapolis","state":"Indiana","country":"United States","latitude":39.76838,"longitude":-86.15804},{"facility":"Iowa Diabetes and Endocrinology Research Center","status":null,"city":"West Des Moines","state":"Iowa","country":"United States","latitude":41.57721,"longitude":-93.71133},{"facility":"Cotton O'Neil Diabetes & Endocrinology","status":null,"city":"Topeka","state":"Kansas","country":"United States","latitude":39.04833,"longitude":-95.67804},{"facility":"MedVadis Research Corporation","status":null,"city":"Waltham","state":"Massachusetts","country":"United States","latitude":42.37649,"longitude":-71.23561}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Have a body mass index (BMI) ≥35.0 kilogram/square meter (kg/m²).\n* Have established cardiovascular (CV) disease with at least 1 of the following:\n\n  * prior myocardial infarction\n  * prior ischemic or hemorrhagic stroke, or\n  * symptomatic peripheral arterial disease\n* Have a history of at least 1 self-reported unsuccessful dietary effort to reduce body weight.\n\nExclusion Criteria:\n\n* Have had acute myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina, or hospitalization due to congestive heart failure within 90 days prior to screening.\n* Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening.\n* Have a prior or planned surgical treatment of obesity.\n* Have a change in body weight greater than 5 kg (11 pounds) within 90 days prior to screening.\n* Have Type 1 diabetes.\n* Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)\n* Have had pancreatitis.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Retatrutide","description":"Administered SC"},{"type":"DRUG","name":"Placebo","description":"Administered SC"}],"primaryOutcomes":[{"measure":"Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline, Week 80"}],"secondaryOutcomes":[{"measure":"Change from Baseline in Body Mass Index (BMI)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Waist Circumference","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Percent Change from Baseline in Total Cholesterol","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Percent Change from Baseline in Triglycerides","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Systolic Blood Pressure (SBP)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Diastolic Blood Pressure (DBP)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Hemoglobin A1c (HbA1c)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Percent Change from Baseline in Fasting Insulin","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Short Form version 2 (SF-36v2) Acute Form Physical Function Domain Score","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Pharmacokinetics (PK): Steady State Area Under the Concentration Time Cure (AUC)","description":"AUC is presented as a single average measure of AUC across the study duration.","timeFrame":"Baseline to Week 80"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05882045"},{"nctId":"NCT05929079","title":"A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight","officialTitle":"A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight: A Randomized Double-Blind, Placebo-Controlled Trial","summary":"The purpose of this study is to is to evaluate the efficacy and safety of retatrutide in participants with type 2 diabetes in participants who have obesity or overweight (J1I-MC-GZBK master protocol) including a subset of participants who have obstructive sleep apnea (OSA) (J1I-MC-GSA2). The study will last about 89 weeks and will include up to 24 visits.","detailedDescription":null,"peptideSlugs":["retatrutide"],"peptideNames":["Retatrutide"],"conditions":["Type 2 Diabetes","Obesity","Overweight","Obstructive Sleep Apnea"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":1152,"dates":{"start":"2023-07-11","primaryCompletion":"2026-06-16","completion":"2026-06-16","firstPosted":"2023-07-03","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":98,"countries":["Argentina","Australia","Brazil","India","Mexico","Romania","Spain","United States"],"locations":[{"facility":"Pinnacle Research Group, LLC","status":null,"city":"Anniston","state":"Alabama","country":"United States","latitude":33.65983,"longitude":-85.83163},{"facility":"Cullman Clinical Trials","status":null,"city":"Cullman","state":"Alabama","country":"United States","latitude":34.17482,"longitude":-86.84361},{"facility":"Preferred Research Partners","status":null,"city":"Little Rock","state":"Arkansas","country":"United States","latitude":34.74648,"longitude":-92.28959},{"facility":"Core Healthcare Group","status":null,"city":"Cerritos","state":"California","country":"United States","latitude":33.85835,"longitude":-118.06479},{"facility":"Velocity Clinical Research, Westlake","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Valley Clinical Trials, Inc.","status":null,"city":"Northridge","state":"California","country":"United States","latitude":34.22834,"longitude":-118.53675},{"facility":"Diablo Clinical Research, Inc.","status":null,"city":"Walnut Creek","state":"California","country":"United States","latitude":37.90631,"longitude":-122.06496},{"facility":"Chase Medical Research, LLC","status":null,"city":"Waterbury","state":"Connecticut","country":"United States","latitude":41.55815,"longitude":-73.0515},{"facility":"Excel Medical Clinical Trials","status":null,"city":"Boca Raton","state":"Florida","country":"United States","latitude":26.35869,"longitude":-80.0831},{"facility":"Teradan Clinical Trials, LLC","status":null,"city":"Brandon","state":"Florida","country":"United States","latitude":27.9378,"longitude":-82.28592},{"facility":"Fleming Island Center for Clinical Research","status":null,"city":"Fleming Island","state":"Florida","country":"United States","latitude":30.0933,"longitude":-81.71898},{"facility":"Therafirst Medical Center","status":null,"city":"Fort Lauderdale","state":"Florida","country":"United States","latitude":26.12231,"longitude":-80.14338},{"facility":"Clinical Site Partners LLC, dba Flourish Research","status":null,"city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366},{"facility":"Quantum Clinical Trials","status":null,"city":"Miami Beach","state":"Florida","country":"United States","latitude":25.79065,"longitude":-80.13005},{"facility":"Renstar Medical Research","status":null,"city":"Ocala","state":"Florida","country":"United States","latitude":29.1872,"longitude":-82.14009},{"facility":"Clinical Research Center of Florida","status":null,"city":"Pompano Beach","state":"Florida","country":"United States","latitude":26.23786,"longitude":-80.12477},{"facility":"Palm Beach Research Center","status":null,"city":"West Palm Beach","state":"Florida","country":"United States","latitude":26.71534,"longitude":-80.05337},{"facility":"Clinical Site Partners, LLC dba Flourish Research","status":null,"city":"Winter Park","state":"Florida","country":"United States","latitude":28.6,"longitude":-81.33924},{"facility":"NeuroTrials Research Inc","status":null,"city":"Atlanta","state":"Georgia","country":"United States","latitude":33.749,"longitude":-84.38798},{"facility":"Centricity Research Rincon Pulmonology","status":null,"city":"Rincon","state":"Georgia","country":"United States","latitude":32.29603,"longitude":-81.23539},{"facility":"East-West Medical Research Institute","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Brengle Family Medicine","status":null,"city":"Indianapolis","state":"Indiana","country":"United States","latitude":39.76838,"longitude":-86.15804},{"facility":"MedVadis Research Corporation","status":null,"city":"Waltham","state":"Massachusetts","country":"United States","latitude":42.37649,"longitude":-71.23561},{"facility":"StudyMetrix Research","status":null,"city":"City of Saint Peters","state":"Missouri","country":"United States","latitude":38.80033,"longitude":-90.62651}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Have a body mass index (BMI) greater than or equal to 27.0 kilogram/square meter (kg/m ²)\n* Have Type 2 Diabetes (T2D)\n* Are on stable treatment for T2D for at least 90 days\n* Have a history of at least one unsuccessful dietary effort to lose body weight.\n\nGSA2 Inclusion Criteria\n\n* Previously diagnosed with OSA\n* Have AHI ≥15 on polysomnography at screening (definition of moderate-to-severe OSA)\n* For participants not on positive airway pressure (PAP) therapy: unable or unwilling to use PAP therapy and have not used PAP for at least 4 weeks prior to screening.\n* If on PAP therapy, have been on PAP therapy for at least 3 consecutive months prior to screening, and willing to temporarily stop using PAP therapy for approximately 7 days prior to each of the sleep study (PSG) visits.\n\nExclusion Criteria:\n\n* Have a self-reported or documented change in body weight \\>5 kg (11 pounds) within 90 days.\n* Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening.\n* Have a prior or planned surgical treatment for obesity.\n* Have Type 1 diabetes\n* Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)\n* Have had pancreatitis\n\nGSA2 Exclusion Criteria\n\n* Use stimulants (for example, modafinil, armodafinil, solriamfetol, pitolisant, amphetamine) less than 3 months prior to screening.\n* Use hypnotics, mirtazapine, opioids, trazodone, and zonisamide less than 3 months prior to screening.\n* Use a dental appliance or other device to treat OSA other than PAP therapy.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Retatrutide","description":"Administered SC"},{"type":"DRUG","name":"Placebo","description":"Administered SC"}],"primaryOutcomes":[{"measure":"Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Apnea-Hypopnea Index (AHI) for GSA2 Subset","description":null,"timeFrame":"Baseline, Week 80"}],"secondaryOutcomes":[{"measure":"Change from Baseline in Body Mass Index (BMI)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Waist Circumference","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Systolic Blood Pressure (SBP)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Diastolic Blood Pressure (DBP)","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Percent Change from Baseline in Total Cholesterol","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Percent Change from Baseline in Triglycerides","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Hemoglobin (A1c) HbA1c %","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Change from Baseline in Fasting Glucose","description":null,"timeFrame":"Baseline, Week 80"},{"measure":"Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)","description":"AUC is presented as a single average measure of AUC across the study duration.","timeFrame":"Baseline through Week 80"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05929079"},{"nctId":"NCT06649344","title":"A Study of HRS9531 Versus Semaglutide Once Weekly as Add-on Therapy to Metformin Monotherapy or in Combination With SGLT2 Inhibitors in Participants With Type 2 Diabetes","officialTitle":"A Phase III,Multicenter,Randomized,Open-label,Parallel-controlled Study Comparing the Efficacy and Safety of HRS9531 With Semaglutide in Subjects With Type 2 Diabetes Mellitus Not Adequately Controlled With Metformin Monotherapy or in Combination With SGLT2 Inhibitors","summary":"The study is being conducted to evaluate the efficacy and safety of HRS9531 once weekly (QW) in subjects with type 2 diabetes mellitus not adequately controlled with metformin monotherapy or in combination with SGLT2 inhibitors compared to Semaglutide QW for 36 weeks and 52 weeks.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Type 2 Diabetes"],"keywords":[],"conditionGroups":[{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Fujian Shengdi Pharmaceutical Co., Ltd.","slug":"fujian-shengdi-pharmaceutical-co-ltd","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":884,"dates":{"start":"2024-10-31","primaryCompletion":"2026-07-18","completion":"2026-07-18","firstPosted":"2024-10-18","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":1,"countries":["China"],"locations":[{"facility":"Zhu Xianyi Memorial Hospital,Tianjin Medical University","status":null,"city":"Tianjin","state":"Tianjin Municipality","country":"China","latitude":39.14222,"longitude":117.17667}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Diagnosed with type 2 diabetes ≥ 90 days；\n2. Stable daily dose(s) for ≥3months prior to screening of : 1) Any metformin formulations ≥1500 mg daily or maximum tolerated (≥1000mg daily). 2) Any metformin formulations ≥1500 mg daily or maximum tolerated (≥1000mg daily) with one type of SGLT-2 inhibitors;\n3. Glycated hemoglobin was 7.5% ≤HbA1c ≤11.0%;\n4. Female patients of childbearing potential and male patients must agree to use highly effective contraception during the trial and for at least 2 months after the last dose of the investigational medicinal drug. Female patients of childbearing potential must test negative for pregnancy at Visit 1 and not be breastfeeding.\n\nExclusion Criteria:\n\n1. Known or suspected allergy or intolerance to the investigational medicinal products or related products；\n2. Acute complications of diabetes occurred during the previous 6 months；\n3. Serious chronic complications of diabetes in the past；\n4. Use other antidiabetic drugs for ≥3months prior to screening ;\n5. Before screening, have disease or treatment that may affect weight; or any previous condition that may affect gastric emptying； or gastrointestinal surgery;\n6. Participation in any clinical trial of an approved or non-approved investigational product/treatment within the last 3 months or 5 half-lives, whichever is longer, prior to screening;\n7. Any conditions that the Investigator judges might not be suitable to participate in the trial.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"HRS9531 Injection","description":"HRS9531 injected subcutaneously once weekly."},{"type":"DRUG","name":"Semaglutide Injection","description":"Semaglutide injected subcutaneously once weekly."}],"primaryOutcomes":[{"measure":"Change in HbA1c","description":"Change from baseline in Glycosylated Haemoglobin after 36 weeks of treatment.","timeFrame":"Week 0 to Week 36"}],"secondaryOutcomes":[{"measure":"Change in body weight","description":"Change from baseline in body weight after 36 weeks of treatment.","timeFrame":"Week 0 to Week 36"},{"measure":"Proportion of Subjects with HbA1c≤6.5%","description":"Proportion of subjects with HbA1c≤6.5% after 36 weeks of treatment.","timeFrame":"Week 0 to Week 36"},{"measure":"Proportion of Subjects with HbA1c<7%","description":"Proportion of subjects with HbA1c\\<7% after 36 weeks of treatment.","timeFrame":"Week 0 to Week 36"},{"measure":"Change in FPG (fasting plasma glucose)","description":"Change from baseline in FPG after 36 weeks of treatment.","timeFrame":"Week 0 to Week 36"},{"measure":"Change in FPG (fasting plasma glucose)","description":"Change from baseline in FPG after 52 weeks of treatment.","timeFrame":"Week 0 to Week 52"},{"measure":"7-points SMPG profiles","description":"Fluctuation of 7-point SMPG. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner,120 minutes after start of dinner, before bedtime.","timeFrame":"Week 0 to Week 36"},{"measure":"Incidence and severity of adverse events","description":"Severity (mild, moderate and severe) is assessed by investigator.","timeFrame":"Week 0 to Week 52+4 weeks follow-up"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06649344"},{"nctId":"NCT07228403","title":"Efficacy and Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome","officialTitle":"A 104-week, Multicenter, Open-label, Single-arm, Phase 3 Extension Trial Investigating the Long-term Safety and Efficacy of Glepaglutide in Adult Patients With Short Bowel Syndrome (SBS) Rolling Over From the EASE SBS 2 or 3 Trials","summary":"The purpose of this study is to understand the safety and efficacy of twice weekly glepaglutide 10 mg in adult patients with short bowel syndrome (SBS), who were previously enrolled in the EASE SBS 2 or EASE SBS 3 trials. Participants currently on these trials will be able to continue their glepaglutide treatment by enrolling in this EASE SBS 6 extension trial. The trial includes a 24-month treatment period, followed by a 4-week safety follow-up period. Participants will attend trial visits, where they may undergo heart tests (electrocardiogram (ECG)), vital sign checks, colonoscopies, blood and urine tests, and physical exams.","detailedDescription":"This trial is a 104-week, multicenter, open-label, single-arm, phase 3 extension trial investigating the long-term safety and efficacy of glepaglutide in adult patients with short bowel syndrome (SBS) rolling over from the EASE SBS 2 or 3 trials.","peptideSlugs":["glepaglutide"],"peptideNames":["Glepaglutide"],"conditions":["Short Bowel Syndrome (SBS)"],"keywords":["Malabsorption Syndromes","Intestinal Diseases","Gastrointestinal Diseases","Digestive System Diseases","Postoperative Complications","Pathologic Processes","Pathological Conditions, Signs and Symptoms","Short Bowel Syndrome"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Zealand Pharma","slug":"zealand-pharma","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":28,"dates":{"start":"2025-12-11","primaryCompletion":"2028-09-18","completion":"2028-12-31","firstPosted":"2025-11-14","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":16,"countries":["Belgium","Canada","France","Germany","Poland","United Kingdom","United States"],"locations":[{"facility":"Mayo Clinic - PPDS","status":null,"city":"Rochester","state":"Minnesota","country":"United States","latitude":44.02163,"longitude":-92.4699},{"facility":"Lied Transplant Center at Nebraska Medical Center","status":null,"city":"Omaha","state":"Nebraska","country":"United States","latitude":41.25626,"longitude":-95.94043},{"facility":"Cleveland Clinic-9500 Euclid Ave","status":null,"city":"Cleveland","state":"Ohio","country":"United States","latitude":41.4995,"longitude":-81.69541},{"facility":"Vanderbilt University Medical Center-Tennesse-1211 21st Ave S","status":null,"city":"Nashville","state":"Tennessee","country":"United States","latitude":36.16589,"longitude":-86.78444},{"facility":"UZ Leuven - PPDS","status":null,"city":"Leuven","state":null,"country":"Belgium","latitude":50.87959,"longitude":4.70093},{"facility":"LHSC - University Hospital","status":null,"city":"London","state":"Ontario","country":"Canada","latitude":42.98339,"longitude":-81.23304},{"facility":"AP-HP - Hôpital Beaujon","status":null,"city":"Clichy","state":"Hauts-de-Seine","country":"France","latitude":48.90018,"longitude":2.30952},{"facility":"Universitätsklinikum Frankfurt","status":null,"city":"Frankfurt am Main","state":"Hesse","country":"Germany","latitude":50.11552,"longitude":8.68417},{"facility":"Universitätsmedizin Rostock","status":null,"city":"Rostock","state":"Mecklenburg-Vorpommern","country":"Germany","latitude":54.0887,"longitude":12.14049},{"facility":"Universitätsklinikum Bonn","status":null,"city":"Bonn","state":"North Rhine-Westphalia","country":"Germany","latitude":50.73438,"longitude":7.09549},{"facility":"Charité - Universitätsmedizin Berlin","status":null,"city":"Berlin","state":"State of Berlin","country":"Germany","latitude":52.52437,"longitude":13.41053},{"facility":"Asklepios Klinik St. Georg","status":null,"city":"Hamburg","state":null,"country":"Germany","latitude":53.55073,"longitude":9.99302},{"facility":"Szpital Skawina sp. z o.o. im. Stanley Dudricka","status":null,"city":"Skawina","state":"Lesser Poland Voivodeship","country":"Poland","latitude":49.97524,"longitude":19.82869},{"facility":"Samodzielny Publiczny Szpitala Kliniczny im. Prof. Witolda Orlowskiego CMKP","status":null,"city":"Warsaw","state":"Masovian Voivodeship","country":"Poland","latitude":52.22977,"longitude":21.01178},{"facility":"Wojewódzki Szpital Specjalistycznyo im. M. Pirogowa w Lodzi","status":null,"city":"Lodz","state":null,"country":"Poland","latitude":51.77058,"longitude":19.47395},{"facility":"St Mark's Hospital (Central Middlesex Hospital)","status":null,"city":"Ealing","state":null,"country":"United Kingdom","latitude":51.51216,"longitude":-0.30204}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Has provided signed informed consent and agrees to comply with protocol requirements.\n* Is being\n\n  1. Actively treated and has completed at least 6 months of glepaglutide treatment in the EASE SBS 2 trial, or\n  2. Actively treated in the EASE SBS 3 trial.\n\nExclusion Criteria:\n\n* Has a condition, disease, or circumstance that, in the opinion of the investigator, would put the patient at any undue risk, prevent completion of the trial, or confound the planned assessments of the trial.\n* Use of GLP-1, GLP-2 (e.g., teduglutide), HGH, DPP-4 inhibitors, somatostatin, or analogs thereof. Note: Prior use of glepaglutide is allowed.\n* Had major protocol deviation(s) (as determined by the sponsor) in the EASE SBS 2 or EASE SBS 3 trial that would affect the conduct of the present trial.\n* Has permanently discontinued the trial treatment because of an AE, assessed as related to the trial drug in the EASE SBS 2 or EASE SBS 3 trial. (Note: AEs are treatment-emergent unless otherwise specified.)\n* If female, is of childbearing potential, pregnant, breastfeeding, intends to become pregnant, or is not using contraceptive methods. Refer to Section 10.2.2 for the definition of contraception.\n* Has a known or suspected hypersensitivity to glepaglutide or related products.\n* Has committed to an institution by virtue of an order issued by the judicial or administrative authorities.\n* Is an employee of the sponsor or investigator or otherwise dependent on them.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Glepaglutide 10 mg","description":"Administered twice weekly by subcutaneous injection for a maximum of 24 months"}],"primaryOutcomes":[{"measure":"Number of treatment emergent adverse events (TEAEs)","description":null,"timeFrame":"From baseline to the safety follow-up visit (A maximum of 25 months)"}],"secondaryOutcomes":[{"measure":"Change in prescribed weekly parenteral support (PS) volume","description":null,"timeFrame":"From baseline to Month 24 (End of Trial)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07228403"},{"nctId":"NCT07407348","title":"A Study in People With Overweight or Obesity to Compare How 2 Different Formulations of Survodutide Are Taken up by the Body","officialTitle":"Bioequivalence of Two Survodutide (BI 456906) Formulations Via Subcutaneous Administration After Multiple Doses (an Open-label, Randomised, Multiple-dose, Crossover Trial)","summary":"The primary objective of this trial is to assess bioequivalence of two formulations of survodutide (formulation A and formulation B6) after multiple-dose treatment in male and female trial participants living with overweight or obesity.","detailedDescription":null,"peptideSlugs":["survodutide"],"peptideNames":["Survodutide"],"conditions":["Healthy","Obesity","Overweight"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Boehringer Ingelheim","slug":"boehringer-ingelheim","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":80,"dates":{"start":"2026-03-11","primaryCompletion":"2027-01-26","completion":"2027-03-02","firstPosted":"2026-02-12","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":1,"countries":["United Kingdom"],"locations":[{"facility":"Quotient Sciences","status":"RECRUITING","city":"Nottingham","state":null,"country":"United Kingdom","latitude":52.9536,"longitude":-1.15047}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Healthy male or female trial participant according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests\n2. Age of 18 to 65 years (inclusive)\n3. Body Mass Index (BMI) of 27.0 to 39.9 Kg/ m\\^2 (inclusive)\n4. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial\n5. For women of child-bearing potential (WOCBP) trial participants: Woman of childbearing potential (WOCBP) trial participants who meet any of the following criteria for a highly effective contraception from at least 28 days before the first administration of trial medication until 28 days after trial completion:\n\n   * Use of combined (estrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal). In case of oral contraception, a barrier method should be used in addition or advised to change to non-oral contraceptives at least 7 days prior to first dose of investigational medicine product (IMP)\n   * Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants). In case of oral contraception, a barrier method should be used in addition or advised to change to non-oral contraceptives at least 7 days prior to first dose of IMP\n   * Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)\n   * Complete abstinence (refraining from heterosexual intercourse during the entire period of risk associated with the study treatment) is considered a highly effective method of contraception only if it is in line with the preferred and usual lifestyle of the trial participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to trial IMP, spermicides only, lactational amenorrhoea method (LAM) and withdrawal are not acceptable methods of contraception\n   * Bilateral tubal ligation/occlusion is considered a highly effective method of contraception, provided that the procedure has not been reversed or failed.\n   * Surgically sterilised (including hysterectomy, bilateral salpingectomy and bilateral oophorectomy)\n   * Postmenopausal, defined as no menses for 1 year without an alternative medical cause\n\nExclusion Criteria:\n\n1. Any finding in the medical examination (including BP, PR) or ECG) deviating from normal and assessed as clinically relevant by the investigator\n2. Repeated measurement of systolic Blood pressure (BP) outside the range of 90 to 150 mmHg, diastolic BP outside the range of 50 to 100 mmHg, or PR outside the range of 50 to 100 bpm\n3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance.\n4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator.\n5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders.\n6. Diseases of the Central nervous system (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders\n7. History of relevant orthostatic hypotension, fainting spells, or blackouts\n8. Relevant chronic or acute infections within the 4 weeks prior to screening Further exclusion criteria apply.","minimumAge":"18 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"COMBINATION_PRODUCT","name":"Formulation A","description":"Formulation A of survodutide"},{"type":"COMBINATION_PRODUCT","name":"Formulation B6","description":"Formulation B6 of survodutide"}],"primaryOutcomes":[{"measure":"Area under the concentration-time curve of survodutide in plasma at steady state over a uniform dosing interval tau (AUC tau,ss)","description":null,"timeFrame":"Up to 239 days."},{"measure":"Maximum measured concentration of survodutide in plasma at steady state over a uniform dosing interval tau (Cmax,ss)","description":null,"timeFrame":"Up to 239 days."}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07407348"},{"nctId":"NCT07564414","title":"A Research Study to Look at How Two Different Doses of CagriSema and One Dose of Semaglutide Help People Living With Obesity With or Without Type 2 Diabetes Lose Weight","officialTitle":"A Clinical Study to Compare Efficacy and Safety of Two Different Doses of CagriSema and Semaglutide in Participants With Obesity With or Without Type 2 Diabetes","summary":"This clinical study is testing how the study medicine CagriSema helps people living with obesity, with or without type 2 diabetes (T2D), lose weight. The purpose of the study is to find out how safe and effective CagriSema is for body weight loss in these participants. Participants will receive either CagriSema or semaglutide, and which treatment participants receive is decided by chance. CagriSema is a new study medicine being tested, while semaglutide is a medicine that doctors can already prescribe. The study will last for about 83 weeks","detailedDescription":null,"peptideSlugs":["semaglutide","cagrilintide"],"peptideNames":["Semaglutide","Cagrilintide"],"conditions":["Obesity","Type 2 Diabetes"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Novo Nordisk","slug":"novo-nordisk","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":2500,"dates":{"start":"2026-05-21","primaryCompletion":"2028-02-23","completion":"2028-04-19","firstPosted":"2026-05-04","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":303,"countries":["Argentina","Australia","Austria","Belgium","Bulgaria","Canada","Czechia","France","Greece","Hungary","Italy","Netherlands","Poland","Portugal","Romania","Slovakia","South Africa","Spain","United States"],"locations":[{"facility":"Uni of Alabama at Birmingham","status":"RECRUITING","city":"Birmingham","state":"Alabama","country":"United States","latitude":33.52066,"longitude":-86.80249},{"facility":"Cahaba Research","status":"RECRUITING","city":"Pelham","state":"Alabama","country":"United States","latitude":33.28567,"longitude":-86.80999},{"facility":"Elligo Health Research Inc","status":"RECRUITING","city":"Gilbert","state":"Arizona","country":"United States","latitude":33.35283,"longitude":-111.78903},{"facility":"Velocity Clinical Research-Phoenix","status":"RECRUITING","city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Arkansas Clinical Research","status":"RECRUITING","city":"Little Rock","state":"Arkansas","country":"United States","latitude":34.74648,"longitude":-92.28959},{"facility":"Woodland Int. Research Group","status":"RECRUITING","city":"Little Rock","state":"Arkansas","country":"United States","latitude":34.74648,"longitude":-92.28959},{"facility":"Headlands Research California, LLC","status":"RECRUITING","city":"Escondido","state":"California","country":"United States","latitude":33.11921,"longitude":-117.08642},{"facility":"Neighborhood Healthcare","status":"RECRUITING","city":"Escondido","state":"California","country":"United States","latitude":33.11921,"longitude":-117.08642},{"facility":"Diabetes & Endocrine Specialists - La Mesa","status":"RECRUITING","city":"La Mesa","state":"California","country":"United States","latitude":32.76783,"longitude":-117.02308},{"facility":"Clinical Trials Research_Sacramento","status":"RECRUITING","city":"Lincoln","state":"California","country":"United States","latitude":38.89156,"longitude":-121.29301},{"facility":"Loma Linda University Faculty Medical Clinics","status":"RECRUITING","city":"Loma Linda","state":"California","country":"United States","latitude":34.04835,"longitude":-117.26115},{"facility":"Pacific Clinical Studies","status":"RECRUITING","city":"Los Alamitos","state":"California","country":"United States","latitude":33.80307,"longitude":-118.07256},{"facility":"Valley Clinical Trials","status":"RECRUITING","city":"Northridge","state":"California","country":"United States","latitude":34.22834,"longitude":-118.53675},{"facility":"Desert Oasis Healthcare","status":"RECRUITING","city":"Palm Springs","state":"California","country":"United States","latitude":33.8303,"longitude":-116.54529},{"facility":"Linda Vista Health Care Ctr","status":"RECRUITING","city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Velocity Clin Res - Van Nuys","status":"RECRUITING","city":"Van Nuys","state":"California","country":"United States","latitude":34.18667,"longitude":-118.44897},{"facility":"Flourish Research - CA","status":"RECRUITING","city":"Walnut Creek","state":"California","country":"United States","latitude":37.90631,"longitude":-122.06496},{"facility":"University of Colorado Hospital","status":"RECRUITING","city":"Aurora","state":"Colorado","country":"United States","latitude":39.72943,"longitude":-104.83192},{"facility":"TBMR & Alcanza","status":"RECRUITING","city":"Clearwater","state":"Florida","country":"United States","latitude":27.96585,"longitude":-82.8001},{"facility":"Northeast Research Institute","status":"RECRUITING","city":"Fleming Island","state":"Florida","country":"United States","latitude":30.0933,"longitude":-81.71898},{"facility":"Northeast Research Institute","status":"RECRUITING","city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"Westside Center For Clinical Research","status":"RECRUITING","city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"Bioclinical Research Alliance","status":"RECRUITING","city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366},{"facility":"New Horizon Research Center","status":"RECRUITING","city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366}],"eligibility":{"criteria":"Inclusion Criteria :\n\n* Male or female (sex assigned at birth, inclusive of all gender identities).\n* Age 18 years or above at the time of signing the informed consent.\n* BMI≥ 35.0 kg/m\\^2.\n* Participants without T2D: No history of T2D and HbA1c \\< 6.5% (48 millimoles per mole (mmol/mol)) Participants with T2D: A history of T2D and HbA1c \\< 10% (\\< 86 mmol/mol). If a participant without a history of diabetes during the screening period receives an HbA1c result of 6.5% (48 mmol/mol) or higher, the investigator or the participant's healthcare provider must confirm the diagnosis of type 2 diabetes before the participant is randomised.\n\nExclusion Criteria:\n\n* A self-reported change in body weight \\> 5% within 90 days before screening, irrespective of medical records.\n* Use of any glucagon-like-peptide-1 receptor agonist (GLP-1 RA), including medication with GLP-1 RA activity, or amylin analogues, including medication with amylin activity, within 6 months before screening.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Cagrisema","description":"Cagrisema (Cagrilintide and Semaglutide) will be administered subcutaneously."},{"type":"DRUG","name":"Semaglutide","description":"Semaglutide will be administered subcutaneously."}],"primaryOutcomes":[{"measure":"Relative change in body weight","description":"Measured as percentage (%).","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"}],"secondaryOutcomes":[{"measure":"Relative change in body weight","description":"Measured as %.","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Change in Body Mass Index (BMI)","description":"Measured as kilograms per square metre (kg/m\\^2).","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Number of participants who achieve greater than or equal to (≥) 30% weight reduction","description":"Measured as count of participants.","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Number of participants who achieve ≥25% weight reduction","description":"Measured as count of participants.","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Number of participants who achieve greater ≥ 20% weight reduction","description":"Measured as count of participants.","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Change in waist circumference","description":"Measured in centimetre (cm).","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Mean change in body weight","description":"Measured in kilograms (kg).","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Number of participants who achieve a BMI less than (<) 30 kg/m^2","description":"Measured as count of participants.","timeFrame":"From randomisation (week 0) to end of treatment (week 72)"},{"measure":"Number of participants who achieve BMI <27 kg/m^2","description":"Measured as count of participants.","timeFrame":"end of treatment (week 72)"},{"measure":"Number of participants who achieve normal BMI, defined as 18.5 lesser than or equal to (≤) BMI < 25 kg/m^2","description":"Measured as count of participants.","timeFrame":"At end of treatment (week 72)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07564414"},{"nctId":"NCT07573163","title":"Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion","officialTitle":"A Randomized Clinical Trial of Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion","summary":"Mild Autonomous Cortisol Secretion (MACS) is a condition in which an adrenal gland produces excess cortisol and is associated with high blood pressure, diabetes, and weight gain. Surgical removal of the adrenal gland (adrenalectomy) is standard treatment, but some patients continue to have metabolic health problems after surgery.\n\nThis randomized study will evaluate whether treatment with tirzepatide after adrenalectomy improves metabolic outcomes in patients with MACS compared with adrenalectomy alone.","detailedDescription":"This prospective, randomized study will enroll adults with MACS and elevated blood pressure who are undergoing unilateral adrenalectomy. Following surgery, participants will be randomized in a 1:1 ratio to one of two groups: adrenalectomy alone or adrenalectomy followed by tirzepatide therapy for 12 months. Tirzepatide will be prescribed and managed by the study team in accordance with current standard-of-care practices, including routine clinical monitoring and dose adjustments.\n\nThe primary focus of the study is to evaluate blood pressure control at 12 months. Secondary outcomes include change in body weight, body mass index, glycemic control, medication burden, and patient-reported quality of life. This study aims to generate preliminary data on the feasibility, safety, and potential additive metabolic benefits of combining pharmacologic incretin-based therapy with surgical management of MACS.","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Mild Autonomous Cortisol Secretion (MACS)","Adrenalectomy; Status"],"keywords":["adrenalectomy","MACS","mild autonomous cortisol secretion"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Alaa Sada","slug":"alaa-sada","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":34,"dates":{"start":"2026-07-27","primaryCompletion":"2028-07-31","completion":"2028-12-31","firstPosted":"2026-05-07","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"University of Pittsburgh Medical Center","status":"RECRUITING","city":"Pittsburgh","state":"Pennsylvania","country":"United States","latitude":40.44062,"longitude":-79.99589}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adults aged 18 years and older\n* Diagnosis of MACS, defined as morning cortisol \\>1.8 mcg/dL after a 1 mg dexamethasone suppression test\n* Elevated blood pressure (SBP ≥120 mmHg or DBP ≥80 mmHg per the 2025 American College of Cardiology/American Heart Association \\[ACC/AHA\\] criteria, or current use of antihypertensive medication)\n* BMI ≥27\n* Undergoing or having undergone adrenalectomy for the treatment of MACS\n\nExclusion Criteria:\n\n* Bilateral adrenal lesions\n* Adrenal malignancy\n* Concurrent primary aldosteronism with MACS\n* Current use of GLP-1 receptor agonists\n* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)\n* Pregnancy or breastfeeding","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Tirzepatide will be initiated at the lowest dose of 2.5 mg once weekly for 4 weeks. The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg."},{"type":"OTHER","name":"Standard medical treatment","description":"Participants will receive postoperative care and follow up per institutional standard-of-care practices"}],"primaryOutcomes":[{"measure":"Change in systolic blood pressure","description":"Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg","timeFrame":"Baseline and 12 months"}],"secondaryOutcomes":[{"measure":"weight","description":"Change in participant weight, Kg","timeFrame":"Baseline and 12 months"},{"measure":"medication","description":"any change in medication expressed as defined daily doses (DDDs)","timeFrame":"Baseline and 12 months reported in WHO defined daily doses (DDDs)"},{"measure":"HbA1c","description":"change in HbA1c levels","timeFrame":"Baseline and 12 months"},{"measure":"quality of life metrics","description":"quality of life metrics will measured using the 36-Item Short Form Health Survey (SF-36) which is a validated measure of health-related quality of life assessing eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 to 100, with higher scores indicating better health status. Domain scores may be analyzed individually or combined using standard scoring algorithms to generate the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, which are norm-based (mean 50, SD 10); higher values reflect better physical and mental health, respectively.","timeFrame":"Baseline and 12 months"},{"measure":"BMI","description":"Any change in BMI in kg/m2","timeFrame":"Baseline and 12 months"}],"publications":[{"pmid":"37700437","citation":"Kanbay M, Copur S, Siriopol D, Yildiz AB, Gaipov A, van Raalte DH, Tuttle KR. Effect of tirzepatide on blood pressure and lipids: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023 Dec;25(12):3766-3778. doi: 10.1111/dom.15272. Epub 2023 Sep 12."},{"pmid":"39084707","citation":"Krumholz HM, de Lemos JA, Sattar N, Linetzky B, Sharma P, Mast CJ, Ahmad NN, Bunck MC, Stefanski A. Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial. Heart. 2024 Sep 16;110(19):1165-1171. doi: 10.1136/heartjnl-2024-324170."},{"pmid":"19632967","citation":"Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D, Fishman E, Kharlip J; American Association of Clinical Endocrinologists; American Association of Endocrine Surgeons. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009 Jul-Aug;15 Suppl 1:1-20. doi: 10.4158/EP.15.S1.1. No abstract available."},{"pmid":"37801655","citation":"Pelsma ICM, Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis. Eur J Endocrinol. 2023 Oct 17;189(4):S88-S101. doi: 10.1093/ejendo/lvad134."},{"pmid":"35799460","citation":"Vanek C, Loriaux L. The 1 mg overnight dexamethasone suppression test: a danger to the adrenal gland? Curr Opin Endocrinol Diabetes Obes. 2022 Aug 1;29(4):403-405. doi: 10.1097/MED.0000000000000752."},{"pmid":"32206602","citation":"Kelsall A, Iqbal A, Newell-Price J. Adrenal incidentaloma: cardiovascular and metabolic effects of mild cortisol excess. Gland Surg. 2020 Feb;9(1):94-104. doi: 10.21037/gs.2019.11.19."},{"pmid":"38137336","citation":"Araujo-Castro M, Reincke M, Lamas C. Epidemiology and Management of Hypertension and Diabetes Mellitus in Patients with Mild Autonomous Cortisol Secretion: A Review. Biomedicines. 2023 Nov 22;11(12):3115. doi: 10.3390/biomedicines11123115."},{"pmid":"38649778","citation":"Prete A, Bancos I. Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches. Nat Rev Endocrinol. 2024 Aug;20(8):460-473. doi: 10.1038/s41574-024-00984-y. Epub 2024 Apr 22."},{"pmid":"33017843","citation":"Morelli V, Ghielmetti A, Caldiroli A, Grassi S, Siri FM, Caletti E, Mucci F, Aresta C, Passeri E, Pugliese F, Di Giorgio A, Corbetta S, Scillitani A, Arosio M, Buoli M, Chiodini I. Mental Health in Patients With Adrenal Incidentalomas: Is There a Relation With Different Degrees of Cortisol Secretion? J Clin Endocrinol Metab. 2021 Jan 1;106(1):e130-e139. doi: 10.1210/clinem/dgaa695."},{"pmid":"33528757","citation":"Sojat AS, Dunjic-Kostic B, Marina LV, Ivovic M, Radonjic NV, Kendereski A, Cirkovic A, Tancic-Gajic M, Arizanovic Z, Mihajlovic S, Vujovic S. Depression: another cortisol-related comorbidity in patients with adrenal incidentalomas and (possible) autonomous cortisol secretion. J Endocrinol Invest. 2021 Sep;44(9):1935-1945. doi: 10.1007/s40618-021-01509-4. Epub 2021 Feb 2."},{"pmid":"29963828","citation":"Reimondo G, Puglisi S, Pia A, Terzolo M. Autonomous hypercortisolism: definition and clinical implications. Minerva Endocrinol. 2019 Mar;44(1):33-42. doi: 10.23736/S0391-1977.18.02884-5. Epub 2018 Jul 2."},{"pmid":"34978855","citation":"Prete A, Subramanian A, Bancos I, Chortis V, Tsagarakis S, Lang K, Macech M, Delivanis DA, Pupovac ID, Reimondo G, Marina LV, Deutschbein T, Balomenaki M, O'Reilly MW, Gilligan LC, Jenkinson C, Bednarczuk T, Zhang CD, Dusek T, Diamantopoulos A, Asia M, Kondracka A, Li D, Masjkur JR, Quinkler M, Ueland GA, Dennedy MC, Beuschlein F, Tabarin A, Fassnacht M, Ivovic M, Terzolo M, Kastelan D, Young WF Jr, Manolopoulos KN, Ambroziak U, Vassiliadi DA, Taylor AE, Sitch AJ, Nirantharakumar K, Arlt W; ENSAT EURINE-ACT Investigators*; ENSAT EURINE-ACT Investigators. Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study. Ann Intern Med. 2022 Mar;175(3):325-334. doi: 10.7326/M21-1737. Epub 2022 Jan 4."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07573163"},{"nctId":"NCT07736261","title":"Drospirenone-Primed Ovarian Stimulation Versus GnRH Antagonist Protocol in Poor Ovarian Responders Undergoing Freeze-All IVF/ICSI","officialTitle":"Drospirenone-Primed Ovarian Stimulation (PPOS) Versus Flexible GnRH Antagonist Protocol in Poor Ovarian Responders Undergoing a Freeze-All Strategy: A Pilot Randomized Controlled Trial","summary":"Participants will:\n\n* Take either drospirenone (a daily pill) or the standard daily injection during their ovarian stimulation cycle, alongside their regular fertility hormone injections\n* Undergo egg retrieval, with all resulting embryos frozen (no fresh embryo transfer in this study)\n* Have a frozen embryo transferred in a later cycle\n* Complete two short questionnaires about their treatment experience - once before starting the injections/pills, and once after the stimulation phase ends\n* Be followed to determine if the embryo transfer results in a pregnancy","detailedDescription":"Single-center, open-label, 1:1 parallel-group pilot RCT, stratified by POSEIDON group. Superiority framing is not used - this pilot is not powered for hypothesis testing on efficacy outcomes; those are reported descriptively with 95% confidence intervals.\n\nFreeze-all is mandated in both arms by protocol (not patient choice). No patient is offered fresh transfer in either arm, so no patient is excluded for requesting one; this is stated explicitly in the consent process so expectations are set at enrollment.\n\nBoth arms use a unified flexible start, triggered by leading follicle diameter reaching 14mm - not a fixed calendar day. Rather than fixing both arms to the same stimulation day (which would not account for individual variability in follicular growth rate, a particular concern in POR), both the antagonist and the drospirenone are initiated on the same physiological trigger: once the leading follicle reaches 14mm, whichever arm the patient is randomized to. This achieves genuine unification across arms (identical starting criterion, applied identically) while remaining individualized to each patient's own stimulation pace. This design has direct precedent, as described in Section 2, and retrospective evidence in POR specifically favors flexible-start over fixed-day dosing on oocyte and fertilization outcomes without increased LH-surge risk.","peptideSlugs":["cetrorelix"],"peptideNames":["Cetrorelix"],"conditions":["Poor Ovarian Reserve","Infertility (IVF Patients)"],"keywords":["poor ovarian response","diminished ovarian reserve","Drospirenone","progestin primed ovarian stimulation","GnRH antagonist","Freeze all"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Ahmed Saad","slug":"ahmed-saad","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE1","PHASE2"],"slugs":["phase-1","phase-2"],"labels":["Phase 1","Phase 2"],"label":"Phase 1 / Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":100,"dates":{"start":"2026-08","primaryCompletion":"2027-10","completion":"2027-11","firstPosted":"2026-07-30","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":1,"countries":["Egypt"],"locations":[{"facility":"Hawaa Fertility Center","status":null,"city":"Banhā","state":"Qalyubia Governorate","country":"Egypt","latitude":30.45977,"longitude":31.1842}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Spontaneous menstrual cycles (21-35 days)\n* Poor ovarian response per Bologna criteria (≥2 of 3): advanced age ≥40 or risk factor for POR; previous poor response (≤3 oocytes with conventional stimulation); abnormal ovarian reserve (AFC \\<7 or AMH \\<1.1 ng/mL)\n* POSEIDON group recorded at enrollment (1-4) for stratified randomization and pre-specified subgroup description - corrects a known limitation of Bologna-only classification, which pools biologically distinct POR phenotypes\n* Indication for IVF/ICSI\n* Willing and able to undergo mandatory freeze-all/FET protocol\n* Signed informed consent, including explicit acknowledgment that fresh transfer is not offered in either study arm\n\nExclusion Criteria:\n\n* Contraindication to ovarian stimulation\n* Known müllerian anomaly\n* Uncontrolled systemic disease\n* 5 prior failed IVF attempts\n* Known contraindication to drospirenone (per product labeling, e.g., renal impairment, adrenal insufficiency, conditions predisposing to hyperkalemia)","minimumAge":"20 Years","maximumAge":"42 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Drospirenone drug","description":"A drug drospirenone in the form of 1 tablet / d from 14 mm follicle till hCG trigger day"},{"type":"DRUG","name":"Cetrorelix 0.25 mg","description":"Cetrorelix a drug injection daily sc. from 14 mm follicle till hCG trigger day"}],"primaryOutcomes":[{"measure":"Metaphase II (Mii) oocytes","description":"Number of mature (MII) oocytes retrieved between drospirenone-PPOS and GnRH antagonist protocols, both using a unified flexible start (leading follicle 14mm), in POR patients undergoing a mandatory freeze-all strategy,","timeFrame":"Day 0"}],"secondaryOutcomes":[{"measure":"Number of oocytes retrieved","description":"Total numbers","timeFrame":"Day 0"},{"measure":"Fertilization rate 2 pronuclei (2PN)","description":"Fertilization rate (2PN) check","timeFrame":"on day 1"},{"measure":"Quality of day-3 embryos","description":"Quality of day-3 embryos (gradeing)","timeFrame":"on day 3"},{"measure":"LH measure","description":"LH measure to follow premature LH surge (LH \\>15 mIU/mL on trigger day) and premature LH rise (LH \\>10 mIU/mL)","timeFrame":"on trigger day ( 2 days before day 0)"},{"measure":"Patient burden score","description":"Patient-reported treatment burden and satisfaction, measured using the validated Controlled Ovarian Stimulation Impact Measure (COSI; four domains - Interference in Daily Life, Injection Burden, Psychological Health, Compliance Worry), administered at day 0. each patient will give a score from 0-4","timeFrame":"Day 0"},{"measure":"CPR ( clinical pregnancy rate)","description":"Clinical pregnancy rate per embryo transfer","timeFrame":"At 6 wks of pregnancy"},{"measure":"Cost per cycle","description":"Cost per stimulation cycle (drug cost only) in EGP","timeFrame":"at day 0"},{"measure":"Number of Day 3 embryos","description":"Measure the numbers of day 3 embryos","timeFrame":"Day 3"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07736261"},{"nctId":"NCT07737522","title":"Myocardial Metabolic Flux in Pulmonary Arterial Hypertension","officialTitle":"Myocardial Metabolic Flux in Patients With Pulmonary Arterial Hypertension (PAH) in Response to GLP-1 Agonist Therapy: a Physiological Study Using 31-Phosphorus MR Spectroscopy","summary":"The rationale for this study is that GLP-1 agonist treatment is likely to influence myocardial substrate utilisation, changing the predominant source of metabolic energy within the heart to a more energetically efficient form. This is represented by a surrogate for improved mitochondrial efficiency with reduction in myocardial lactate levels (produced by inefficient myocardial glycolysis, prevalent in the ventricles of patients with pulmonary hypertension), which can be measured by 31P-magnetic resonance spectroscopy (31P-MRS).","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Pulmonary Arterial Hypertension"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Imperial College London","slug":"imperial-college-london","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":32,"dates":{"start":"2026-10-01","primaryCompletion":"2028-10-01","completion":"2029-04-01","firstPosted":"2026-07-30","resultsPosted":null,"lastUpdated":"2026-07-30"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n\\- 1. Diagnosis of Group 1 PAH confirmed by right heart catheterisation under the National Pulmonary Hypertension Service, Royal Brompton Hospital, part of GSTT Foundation Trust 2. Age over 18, less than 85 years 3. Able to give informed consent 4. On a stable dose of PAH-specific therapies (e.g., ERA, PDE5i) for at least 3 months.\n\n5\\. Clinically justified prescription of GLP-1 agonist Semaglutide based on following criteria: BMI \\> 30 or BMI \\> 27 with at least one cardiovascular co-morbidity (systemic hypertension, diabetes, pre-diabetes, COPD, atrial fibrillation, dyslipidaemia, sleep disordered breathing)\n\nExclusion Criteria:\n\n* • 1. Pregnancy\n\n  * 2\\. Myocardial infarction within the previous 3 months\n  * 3\\. Contraindications to MRI: Pacemakers, metallic implants, or severe claustrophobia.\n  * 4\\. Severe renal impairment: eGFR \\< 15ml/min/1.73m.\n  * 5\\. Current use of SGLT2 inhibitors or GLP-1 agonist therapy (which significantly alter fuel substrate preference) or insulin therapy that cannot be held for the fasting scan","minimumAge":"18 Years","maximumAge":"85 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"GLP-1 agonist","description":"Semaglutide"}],"primaryOutcomes":[{"measure":"Change in the phosphocreatine-to-adenosine triphosphate (31PCr/ATP) ratio between baseline and follow up in response to treatment with GLP-1 agonist","description":null,"timeFrame":"12 weeks"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07737522"},{"nctId":"NCT00569127","title":"Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor","officialTitle":"Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients","summary":"This randomized phase III trial studies octreotide acetate and recombinant interferon alfa-2b to see how well it works compared to octreotide acetate and bevacizumab in treating patients with high-risk neuroendocrine tumors that have spread to other places in the body (metastatic) or spread from where it started to nearby tissue or lymph nodes (locally advanced). Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.","detailedDescription":"PRIMARY OBJECTIVES:\n\nI. To compare central review-based progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide (octreotide acetate) plus bevacizumab, or depot octreotide plus interferon (recombinant interferon alfa-2b).\n\nSECONDARY OBJECTIVES:\n\nI. To compare overall survival, time to treatment failure and traditionally reported progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.\n\nII. To compare objective response (confirmed and unconfirmed complete response \\[CR\\] and partial response \\[PR\\]) in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.\n\nIII. To compare the toxicity profile of patients treated with these two regimens.\n\nTERTIARY OBJECTIVES:\n\nI. To assess the prognostic and predictive value of vascular endothelial growth factor (VEGF) expression in relation to progression-free survival and treatment effect.\n\nII. To compare response of 5HIAA, chromogranin A and neuronspecific enolase among patients with elevated levels at baseline between patients treated with octreotide plus interferon versus octreotide plus bevacizumab.\n\nIII. To assess and compare the prognostic and predictive value of the combination of In-111 pentetreotide somatostatin-receptor scintigraphy (SRS) and computed tomography (CT) vs. CT in relation to progression-free survival (PFS).\n\nIV. To assess and compare the prognostic and predictive value of the combination of SRS and CT vs. CT in relation to overall survival (OS) and time to treatment failure (TTF).\n\nOUTLINE: Patients are randomized to 1 of 2 treatment arms.\n\nARM I: Patients receive octreotide acetate intramuscularly (IM) and bevacizumab intravenously (IV) over 30-90 minutes on day 1.\n\nARM II: Patients receive octreotide acetate IM on day 1 and recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3, 5, 8, 10, 12, 15, 17, and 19.\n\nTreatment in both arms repeats every 21 days in the absence of disease progression or unacceptable toxicity.\n\nAfter completion of study treatment, patients are followed up every 2-6 months for up to 3 years.","peptideSlugs":["octreotide"],"peptideNames":["Octreotide"],"conditions":["Colorectal Neuroendocrine Tumor G1","Gastric Neuroendocrine Tumor G1","Neuroendocrine Neoplasm","Neuroendocrine Tumor","Neuroendocrine Tumor G2"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":427,"dates":{"start":"2007-12-01","primaryCompletion":"2015-01-01","completion":"2027-01-31","firstPosted":"2007-12-06","resultsPosted":"2016-04-28","lastUpdated":"2026-07-29"},"hasResults":true,"locationCount":493,"countries":["United States"],"locations":[{"facility":"Providence Hospital","status":null,"city":"Mobile","state":"Alabama","country":"United States","latitude":30.69436,"longitude":-88.04305},{"facility":"Fairbanks Memorial Hospital","status":null,"city":"Fairbanks","state":"Alaska","country":"United States","latitude":64.83778,"longitude":-147.71639},{"facility":"Mercy Hospital Fort Smith","status":null,"city":"Fort Smith","state":"Arkansas","country":"United States","latitude":35.38592,"longitude":-94.39855},{"facility":"NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro","status":null,"city":"Jonesboro","state":"Arkansas","country":"United States","latitude":35.8423,"longitude":-90.70428},{"facility":"University of Arkansas for Medical Sciences","status":null,"city":"Little Rock","state":"Arkansas","country":"United States","latitude":34.74648,"longitude":-92.28959},{"facility":"Highlands Oncology Group - Rogers","status":null,"city":"Rogers","state":"Arkansas","country":"United States","latitude":36.33202,"longitude":-94.11854},{"facility":"Kaiser Permanente-Anaheim","status":null,"city":"Anaheim","state":"California","country":"United States","latitude":33.83529,"longitude":-117.9145},{"facility":"Arroyo Grande Community","status":null,"city":"Arroyo Grande","state":"California","country":"United States","latitude":35.11859,"longitude":-120.59073},{"facility":"PCR Oncology","status":null,"city":"Arroyo Grande","state":"California","country":"United States","latitude":35.11859,"longitude":-120.59073},{"facility":"Kaiser Permanente-Baldwin Park","status":null,"city":"Baldwin Park","state":"California","country":"United States","latitude":34.08529,"longitude":-117.9609},{"facility":"Kaiser Permanente-Bellflower","status":null,"city":"Bellflower","state":"California","country":"United States","latitude":33.88168,"longitude":-118.11701},{"facility":"Alta Bates Summit Medical Center-Herrick Campus","status":null,"city":"Berkeley","state":"California","country":"United States","latitude":37.87159,"longitude":-122.27275},{"facility":"Providence Saint Joseph Medical Center/Disney Family Cancer Center","status":null,"city":"Burbank","state":"California","country":"United States","latitude":34.18084,"longitude":-118.30897},{"facility":"Mills-Peninsula Medical Center","status":null,"city":"Burlingame","state":"California","country":"United States","latitude":37.5841,"longitude":-122.36608},{"facility":"Kaiser Permanente-Fontana","status":null,"city":"Fontana","state":"California","country":"United States","latitude":34.09223,"longitude":-117.43505},{"facility":"Marin General Hospital","status":null,"city":"Greenbrae","state":"California","country":"United States","latitude":37.94854,"longitude":-122.5247},{"facility":"Kaiser Permanente South Bay","status":null,"city":"Harbor City","state":"California","country":"United States","latitude":33.79002,"longitude":-118.29785},{"facility":"Kaiser Permanente-Irvine","status":null,"city":"Irvine","state":"California","country":"United States","latitude":33.66946,"longitude":-117.82311},{"facility":"Kaiser Permanente Los Angeles Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Los Angeles General Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"USC / Norris Comprehensive Cancer Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Kaiser Permanente West Los Angeles","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Cedars-Sinai Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Sutter Cancer Research Consortium","status":null,"city":"Novato","state":"California","country":"United States","latitude":38.10742,"longitude":-122.5697}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Patient must have unresectable metastatic or locally advanced, low- or intermediate-grade neuroendocrine carcinoma\n\n  * NOTE: pathology report must state one of the following: carcinoid, low-grade or well-differentiated neuroendocrine carcinoma, atypical carcinoid, intermediate-grade or moderately differentiated neuroendocrine carcinoma; patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, or goblet cell carcinoid are not eligible; patient must not have osseous metastasis as only site of disease; patients with medullary thyroid carcinoma or islet cell carcinoma are not eligible; if pathology report states only neuroendocrine carcinoma, pathology subtype must be reconfirmed\n  * Occasionally, it is not possible to establish tumor grade on fine-needle aspiration (FNA) cytology material; if a new biopsy is needed, a core needle biopsy should be obtained whenever possible\n* Patient must have high risk disease as defined by at least one of the following:\n\n  * Progressive disease\n  * Refractory carcinoid syndrome while receiving octreotide (defined by \\> 2 flushing episodes/day or \\> 4 bowel movements/day)\n  * Atypical histology and more than 6 lesions\n  * Metastatic colorectal carcinoid; patients with metastatic cecal or appendiceal carcinoid tumor are not eligible unless the tumors fit into one of the other high-risk categories (a, b, or c above)\n  * Metastatic gastric carcinoid\n* Patient must have measurable disease; CT or magnetic resonance imaging (MRI) used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; these scans also must be submitted for central radiology review\n* Institutions are required to submit CT/MRI scans and archived tissue for pathology review; furthermore, institutions are required to seek additional patient consent for submission of octreotide scans, and submission of blood and use of archived tissue for correlative studies\n* If patient consents to the submission of octreotide scans, the patient must also be registered to Registration Step 2\n* Patient may have had up to one prior regimen of cytotoxic chemotherapy; at least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects\n* Patient may have had prior hepatic artery embolization; at least 28 days must have elapsed since embolization and there must be residual measurable disease; chemoembolization will be considered as one prior chemotherapy regimen\n* Patient must not have received prior interferon, bevacizumab or any other therapy targeting VEGF or VEGF receptors\n* Patient may have received prior therapy targeting stem cell factor receptor (c-kit), abelson murine leukemia viral oncogene homolog 1 (abl), platelet-derived growth factor receptor (PDGFR), mammalian target of rapamycin (mTOR), and somatostatin receptors (not counted toward prior cytotoxic chemotherapy)\n* Prior radiation is allowed; there must be measurable disease; if prior therapies include peptide receptor radiotherapy, the target lesion(s) must have shown disease progression; at least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects\n* Patients must have recovered from any prior surgery; one week must have elapsed from the time of a minor surgery and 4 weeks from major surgery\n* At least 21 days must have elapsed since any prior octreotide LAR depot treatment\n* Patient must have a Zubrod performance status of 0-2\n* Absolute neutrophil count (ANC) \\> 1,500/mcl\n* Hemoglobin \\> 8 g/dl\n* Platelets \\> 100,000/mcl\n* Serum bilirubin \\< 1.5 x institutional upper limit of normal (IULN)\n* Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =\\< 2.5 x IULN\n* Serum creatinine \\< 1.5 mg/dL\n* Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio; for UPC ratio \\> 0.5, 24-hour urine protein must be obtained and the level must be \\< 1,000 mg for patient enrollment; these results must be obtained within 28 days prior to registration\n\n  * Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm\n* Patients not on anticoagulation must have prothrombin time (PT) and partial thromboplastin time (PTT) =\\< 1.1 x lULN obtained within 28 days prior to registration; patients on full-dose anticoagulation (warfarin or low molecular weight heparin) are eligible provided that both of the following criteria are met:\n\n  * The patient has an in-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n  * The patient has no active bleeding or pathological condition that carries a high risk of bleeding such as varices\n* Patient must not have history or evidence of clinically significant peripheral vascular disease such as non-healing peripheral ulcers or claudication\n* Patient must not have a history of primary brain tumor or metastatic cancer to the brain; brain imaging studies are not required for eligibility if the patient has no neurological signs or symptoms; if brain imaging studies are performed, they must be negative for disease\n* Patient must not have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration\n* Patient must not have history within the past 5 years or presence of bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring packed red blood cells (pRBC) transfusion\n* Patient must not have a serious (requiring active medical therapy with medication or medical device under the supervision of a physician) non-healing wound, ulcer, or bone fracture\n* Patient must not have recent history (within 6 months prior to registration) of these arterial thromboembolic events: transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction, or New York Heart Association grade II or higher congestive heart failure\n* Patients with a history of hypertension must be well-controlled (blood pressure \\< 150/90), on a stable regimen of antihypertensive therapy\n* Patient must not have hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia\n* Patient must not plan to use any other concurrent chemotherapy, immunotherapy, hepatic artery embolization, hepatic artery chemoembolization, radiofrequency ablation, other tumor ablative procedure or radiotherapy while on protocol treatment\n* Patient must not be pregnant or nursing because bevacizumab may be harmful to the developing fetus and newborn; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout protocol treatment and for up to 6 months following discontinuation of bevacizumab\n* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years\n* All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines\n* At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional re view board approval for this study has been entered into the data base\n* REGISTRATION STEP 2 - SPECT SUBSTUDY\n* Patient must have registered to the main study\n* Patient must have consented to the submission of octreotide scans\n* An octreotide scan obtained within 28 days prior to Registration Step 1 must be available for submission","minimumAge":null,"maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"BIOLOGICAL","name":"Bevacizumab","description":"Given IV"},{"type":"OTHER","name":"Laboratory Biomarker Analysis","description":"Correlative studies"},{"type":"DRUG","name":"Octreotide Acetate","description":"Given IM"},{"type":"BIOLOGICAL","name":"Recombinant Interferon Alfa-2b","description":"Given SC"}],"primaryOutcomes":[{"measure":"Central Review-based Progression-Free Survival","description":"From date of randomization (which is the date of registration) to date of first documentation of progression based on Central Radiological Review of the appropriate CT or MRI scans, or symptomatic deterioration (as defined in Section 10.2e)), or development of new lesions or disease not identified on CT or MRI, or death due to any cause. Patients who have a local assessment of progression based on imaging, but for whom central review does not concur, will be censored at the last Central Radiological Review date, unless subsequent scans or documentation of symptomatic deterioration provides evidence of progression. Patients last known not to have progressed are censored at the date of last contact. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not progressed prior to that time.","timeFrame":"Up to 3 years"}],"secondaryOutcomes":[{"measure":"Overall Survival","description":"From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.","timeFrame":"Up to 7 years"},{"measure":"Time to Treatment Failure","description":"From date of randomization (which is the date of registration) to date of first observation of progressive disease (as defined in Section 10.2d), death due to any cause, symptomatic deterioration (as defined in Section 10.2e), or discontinuation of treatment. This has been calculated using Central-Review based progression events. Patients last known not to have failed treatment are censored at date last known not to have failed. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not failed treatment prior to that time.","timeFrame":"Up to 3 years"},{"measure":"Local Progression-Free Survival (Investigator Assessed)","description":"From date of randomization (which is the date of registration) to date of first documentation of progression \\[per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as defined in Section 10.2d\\] or symptomatic deterioration (as defined in Section 10.2e), or death due to any cause. Patients last known not to have progressed are censored at date of last contact. Progression (Section 10.2d) includes one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over smallest sum observed using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of new lesion/site; or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration (Section 10.2e) is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.","timeFrame":"Up to 3 years"},{"measure":"Objective Response (Confirmed and Unconfirmed Complete Response and Partial Response)","description":"Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is disappearance of all measurable and non-measurable disease, and no new lesions; Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed response is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.","timeFrame":"Up to 3 years"},{"measure":"Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug","description":"Only adverse events that are possibly, probably or definitely related to study drug are reported.","timeFrame":"Up to 3 years"}],"publications":[{"pmid":"28384065","citation":"Yao JC, Guthrie KA, Moran C, Strosberg JR, Kulke MH, Chan JA, LoConte N, McWilliams RR, Wolin EM, Mattar B, McDonough S, Chen H, Blanke CD, Hochster HS. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518. J Clin Oncol. 2017 May 20;35(15):1695-1703. doi: 10.1200/JCO.2016.70.4072. Epub 2017 Apr 6."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT00569127"},{"nctId":"NCT01542021","title":"Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer","officialTitle":"Establishing a Neo-Adjuvant Platform for Developing Targeted Agents: Androgen Deprivation Therapy Prior to Prostatectomy for Patients With Intermediate and High Risk Prostate Cancer","summary":"Degarelix is an approved drug that is used to treat prostate cancer by lowering testosterone levels in the body.\n\nDegarelix is commonly given with radiation for prostate cancer, but less frequently with surgery since there has been no proven benefit with this approach.\n\nThe investigators do not expect the patient to benefit directly from treatment with degarelix since their prostate will be removed shortly after the drug is given. Instead, the investigators hope to learn about how degarelix and other treatment that lowers your testosterone effects prostate cancer cells and use this information to develop better treatments in the future.","detailedDescription":null,"peptideSlugs":["degarelix"],"peptideNames":["Degarelix"],"conditions":["Prostate Cancer","Prostatic Adenocarcinoma"],"keywords":["prostate","Degarelix","injections","radical prostatectomy","11-182"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Memorial Sloan Kettering Cancer Center","slug":"memorial-sloan-kettering-cancer-center","class":"OTHER"},"collaborators":[{"name":"Ferring Pharmaceuticals","slug":"ferring-pharmaceuticals","class":"INDUSTRY"}],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":41,"dates":{"start":"2012-02-24","primaryCompletion":"2024-09-30","completion":"2024-09-30","firstPosted":"2012-03-01","resultsPosted":"2026-07-29","lastUpdated":"2026-07-29"},"hasResults":true,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Memorial Sloan Kettering Cancer Center","status":null,"city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Histologic confirmation of prostatic adenocarcinoma by MSKCC inclusive of the following:\n* 3 or more positive biopsy cores or equivalent tumor specimen as confirmed by pathologist\n* At least 2 cores containing ≥3 mm of tissue with carcinoma or equivalent tumor specimen as confirmed by pathologist\n* A primary tumor Gleason score ≥ 7\n* Adequate primary biopsy tissue or equivalent tumor specimen as confirmed by pathologist available for protocol required analysis (i.e. bladder or TURP specimen)\n* Planning to have or have had a radical prostatectomy (RP) at MSKCC\n* Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for RP\n* Karnofsky performance status \\>70% (Appendix A)\n* Sexually active fertile subjects, and their partners, must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the dose of study drug(s) for Cohorts 1 , 2 and 4, and for 3 months after the surgery for Cohort 3\n* For cohorts 1,2 and 4 only:, non-castrate testosterone level (\\>100 ng/dL)\n* For cohort 3 only:, 1-6 months of androgen deprivation therapy (gonadotropin hormone releasing analogs with or without an anti-androgen) prior to prostatectomy with a castrate testosterone level of \\<50 ng/dL within 1 month prior to prostatectomy.\n\nExclusion Criteria:\n\n* Histologic variants in the primary tumor (histologic variants other than adenocarcinoma)\n* Current or prior chemotherapy\n* The use of the 5-alpha-reductase inhibitor dutasteride must be discontinued within 4 weeks of degarelix injection for Cohort 1, 2 and 4, and within 4 weeks of surgery for Cohort 3.\n* Saw palmetto administered with the intent to treat the patient's malignancy within 1 week of degarelix injection for Cohorts 1, 2 and 4, and for within 1 week of surgery for Cohort 3\n* Current or prior radiation therapy to the prostate\n* Active infection or intercurrent illness\n* Concomitant therapy with any other experimental drug\n* For cohorts 1, 2 and 4 only:, current or prior hormonal therapy (e.g., gonadotropin hormone releasing analogs, megestrol acetate, or antiandrogens) are exclusionary","minimumAge":"18 Years","maximumAge":null,"sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"degarelix injection","description":"Treatment will consist of a single 240 mg injection of degarelix 4 ± 1 day before radical prostatectomy, depending on treatment arm."},{"type":"DRUG","name":"degarelix injection","description":"Treatment will consist of a single 240 mg injection of degarelix 7 ± 1 day before radical prostatectomy, depending on treatment arm."},{"type":"DRUG","name":"androgen deprivation therapy","description":null}],"primaryOutcomes":[{"measure":"Percent Change in Prostate Cancer Cell Proliferation (Ki-67 Levels)","description":"The primary endpoint is the change in the rate of proliferation (Ki-67), as evaluated by IHC in anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the RP specimen. The levels in pre-treatment biopsy serve as the baseline. Ki-67 is a widely accepted nuclear marker for cell proliferation.","timeFrame":"Baseline and up to 2 years"}],"secondaryOutcomes":[{"measure":"Median Percentage of Cells From Biopsy and Surgery That Are Positive For Ki-67","description":"The secondary endpoint is PTEN status by IHC in the diagnostic biopsy and RP specimens. PTEN status will be determined by an IHC method that has been validated using control prostate cell lines and tissues at MSKCC. The PTEN status will be reported in binary fashion as \"retained\" (diffuse moderate immunoreactivity retained in benign glands as well as adenocarcinoma on 100X magnification) or \"null\" (complete loss of nuclear and cytoplasmic immunoreactivity in tumor cells while expression is retained in surrounding stroma.","timeFrame":"up to 2 years"},{"measure":"Record Participant Biomarker Results and Correlates of Response","description":"through expression profiling of prostate cancer after three time intervals of androgen deprivation therapy and correlate with PTEN and ERG status, proliferation rate, apoptotic rate, and histologic response","timeFrame":"Up to 14+/- days"}],"publications":[{"pmid":"34350976","citation":"Zengerling F, Jakob JJ, Schmidt S, Meerpohl JJ, Blumle A, Schmucker C, Mayer B, Kunath F. Degarelix for treating advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT01542021"},{"nctId":"NCT05796388","title":"A Study of Virtual Reality and Linaclotide for IBS-C","officialTitle":"A Pilot Study to Evaluate the Efficacy and Safety of Virtual Reality in Combination With Linaclotide for the Treatment of Adults With IBS and Constipation Predominance","summary":"The purpose of this study is to determine if adult patients with IBS-C will report an overall greater improvement in IBS symptoms and quality of life when treated with a combination of linaclotide (standard of care medication) and immersive virtual reality (VR) therapy compared to those treated with linaclotide and sham (placebo) VR therapy.","detailedDescription":"The primary aim of this study will be to assess the benefits of disease-targeted VR combined with linaclotide, compared to sham VR combined with linaclotide, in patients with IBS-C as defined by Rome IV criteria. The investigators hypothesize that compared to patients receiving sham VR and linaclotide, IBS-C patients receiving combination therapy with active VR and linaclotide will achieve statistically significant and clinically meaningful improvements in disease-targeted health-related quality of life while demonstrating improvements in global IBS symptoms, including abdominal pain.\n\nAims\n\n1. Evaluate changes in quality of life using the validated IBS-QoL (primary outcome);\n2. Evaluate global improvement in IBS symptoms using the validated IBS-SSS;\n3. Assess global improvement in IBS symptoms using the validated Abdominal Scoring system (11);\n4. Evaluate improvement in abdominal pain using a numerical rating system (NRS);\n5. Assess improvement in constipation using the Bristol Stool Form Scale (BSFS);\n6. Evaluate response to bloating using the validated Mayo bloating questionnaire (12);\n7. Assess response to coexisting psychological distress using the validated HADs questionnaire;\n8. Evaluate changes in work productivity using the validated WPAI.","peptideSlugs":["linaclotide"],"peptideNames":["Linaclotide"],"conditions":["Irritable Bowel Syndrome With Constipation"],"keywords":["Virtual reality","IBS-C"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Mayo Clinic","slug":"mayo-clinic","class":"OTHER"},"collaborators":[{"name":"Cedars-Sinai Medical Center","slug":"cedars-sinai-medical-center","class":"OTHER"},{"name":"AbbVie","slug":"abbvie","class":"INDUSTRY"},{"name":"Ironwood Pharmaceuticals, Inc.","slug":"ironwood-pharmaceuticals-inc","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":65,"dates":{"start":"2024-05-31","primaryCompletion":"2026-10","completion":"2026-10","firstPosted":"2023-04-03","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Mayo Clinic Florida","status":"RECRUITING","city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adult men and women (18-70) who meet Rome IV criteria for IBS-C.\n* Patients will be required to score below 65 points on the IBS Quality of Life (IBS-QOL) instrument, indicating a score consistent with at least moderate HRQOL (Health-related quality of life) impairment.\n\nExclusion Criteria:\n\n* Patients will be excluded from the study if they have a comorbid disorder that may confound the diagnosis of IBS, including celiac disease, inflammatory bowel disease, autoimmune disorders that affect the GI system, history of bowel resection, HIV/AIDS, diabetes with HgA1c \\>7.0, neuroendocrine tumors, microscopic colitis, lactase deficiency, eosinophilic bowel disease, acute intermittent porphyria, or any other condition that a licensed physician believes can mimic IBS symptoms and undermine diagnostic certitude.\n* Patients with severe depression, defined as a score equal to or greater than two standard deviations (SDs) on the NIH PROMIS depression scale, or those with suicidal ideations, will also be excluded and provided with standard resources to support their mental health and referred back to their primary care provider, a member of the study team will follow up with the PCP to ensure the communication was received.\n* Patients using regular doses of opioid medications will also be excluded given the often-severe impact of opioids on GI motility and potential for pharmacological visceral hyperalgesia.\n* Patients will also be excluded from the study if they do not meet Rome IV criteria for IBS-C,\n* have a known seizure disorder,\n* if symptoms are thought to represent an organic disorder,\n* if they have had prior surgery to the colon,\n* if symptoms represent a known pelvic floor disorder,\n* if the patient is abusing alcohol,\n* or if the patient cannot actively participate in the study for any other reason (e.g., inability to understand English as the VR program is in English only).\n* Patients previously treated with linaclotide who reported side effects,\n* those currently on linaclotide (any dose),\n* and those who did not note an improvement in IBS-C symptoms in the past while on linaclotide will also be excluded.","minimumAge":"18 Years","maximumAge":"70 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DEVICE","name":"Virtual Reality","description":"Both groups will receive standard of care linaclotide 290 mcg."}],"primaryOutcomes":[{"measure":"Changes in IBS symptoms","description":"Measure global changes in IBS symptoms using the validated IBS severity scoring system (IBS-SSS) at week 8 compared to baseline, for patients treated with a combination of linaclotide and immersive VR and compare to those treated with linaclotide and sham VR therapy. IBS-SSS is a composite score of abdominal pain, number of days with abdominal pain, bloating/distension, satisfaction with bowel habits, and IBS-related quality of life (QoL). Each measure is rated from 0 to 100, with total scores ranging from 0 to 500. \\< 175 for mild IBS, 175-300 for moderate IBS, and \\> 300 for severe IBS.","timeFrame":"End of study week 8 compared to baseline"}],"secondaryOutcomes":[{"measure":"Measure change in quality of life, using the validated IBS-QoL","description":"Irritable Bowel Syndrome-Quality of Life Measure (IBS-QOL) The individual responses to the 34 items are summed and averaged for a total score and then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS specific quality of life.","timeFrame":"Week 8"},{"measure":"Measure changes in abdominal pain using the NRS","description":"The Abdominal Pain Numeric Rating Scale (NRS) patients are asked to circle the number between 0 and 10, 0 and 20 or 0 and 100 that fits best to their pain intensity. Zero usually represents 'no pain at all' whereas the upper limit represents 'the worst pain ever possible'.","timeFrame":"Week 8"},{"measure":"Measure changes in bloating using the Mayo bloating questionnaire","description":"A 40-item questionnaire to understand the daily impact of symptoms of bloating and distension","timeFrame":"week 8"},{"measure":"Measure changes in psychological distress using the HADs questionnaire;","description":"The Hospital Anxiety and Depression Scale (HADs) consists of 14 items and consists of two subscales: anxiety and depression. Each item is rated on a four-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represents 'borderline' and 0-7 'normal'","timeFrame":"week 8"},{"measure":"Measure changes in work productivity using the validated WPAI.","description":"The Work Productivity and Activity Impairment (WPAI) questionnaire consists of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed other reasons; 4 = hours actually worked; 5 = degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6 = degree health affected productivity in regular unpaid activities","timeFrame":"Week 8"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05796388"},{"nctId":"NCT06305182","title":"Metreleptin in Anorexia Nervosa","officialTitle":"Metreleptin in Anorexia Nervosa, Randomized Controlled Trial; Effects on Depressive Symptoms and Concomitant Changes in Brain Connectivity","summary":"The treatment of anorexia nervosa often proves to be difficult. There are no drugs that work specifically for the treatment of anorexia nervosa. Experimental administration of metreleptin (synthetically produced leptin) to patients with anorexia nervosa has produced positive results. This study tests the effect of metreleptin in comparison with placebo, which could potentially make treatment easier. The aim of the study is to investigate whether treatment with metreleptin can help to reduce the symptoms of anorexia nervosa and improve mood and weight.","detailedDescription":"Anorexia nervosa (AN) mainly affects young people, especially young women. AN is one of the most lethal psychiatric disorders. Treatment often proves to be very difficult, and the course of AN is frequently chronic. Specific pharmacological therapies for AN are lacking. Recent studies have shown that metabolic alterations play a major role in the etiology and pathogenesis of AN. An important metabolic alteration involved in the etiology and pathogenesis of AN is the hormone leptin. Patients with AN show hypoleptinemia. The role of hypoleptinemia in the neuroendocrine adaptation to starvation seems to induce emotional, cognitive, and behavioral symptoms of AN. From a theoretical point of view, pharmacotherapy aimed at increasing leptin levels in patients with AN has great therapeutic potential. Recently, positive effects following the experimental administration of subcutaneous metreleptin have been observed in small number of young patients with severe AN. Importantly, no side effects have been observed. For all these reasons, the present study will investigate, using a double-blind design, the therapeutic effect of metreleptin in patients with AN. Metreleptin will be administrated to 50 inpatients with AN: 25 patients will receive verum and 25 will receive placebo for 14 days. The primary objectives of this study are the amelioration of mood and weight. Secondary objectives are the investigation of functional brain connectivity, AN symptoms, as well as hematological, blood chemistry and neuroendocrinological parameters.","peptideSlugs":["metreleptin"],"peptideNames":["Metreleptin"],"conditions":["Anorexia Nervosa"],"keywords":["Anorexia Nervosa","Leptin","Metreleptin","Weight gain","Depression"],"conditionGroups":[{"slug":"brain-health","label":"Brain health"}],"sponsor":{"name":"Gabriella Milos","slug":"gabriella-milos","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":50,"dates":{"start":"2024-05-31","primaryCompletion":"2026-12-31","completion":"2026-12-31","firstPosted":"2024-03-12","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":1,"countries":["Switzerland"],"locations":[{"facility":"Eating Disorder Unit, Clinic of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich","status":"RECRUITING","city":"Zurich","state":"Canton of Zurich","country":"Switzerland","latitude":47.36667,"longitude":8.55}],"eligibility":{"criteria":"Main key inclusion criteria:\n\n* Current diagnosis of AN according to fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirmed with Structured Clinical Interview for DSM-5 (SCID-5)\n* BMI \\> 13 kg/m2; BMI ≤ 18 kg/m2; body weight ≥ 35 kg\n* Hospitalisation in the Eating Disorders Unit, Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital of Zurich\n* Ability to understand German language\n* Age range: 17 - 65 years\n* Depressive symptoms: HAMD-17 ≥ 8\n* Negative urine pregnancy test, non-lactating and double birth control\n* Informed Consent as documented by signature\n\nMain key exclusion criteria:\n\n* Illicit drug intake within last month; current alcohol use disorder\n* Severe psychiatric and/or severe somatic comorbidities; f. e. lifetime diagnosis of schizophrenia, bipolar disorder, inflammatory bowel disorders, diabetes mellitus, autoimmune disorders, pancreatitis, neurological disorders, cancer including lymphoma\n* Acute suicidality or current serious non-suicidal self-injury","minimumAge":"17 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Metreleptin","description":"Metreleptin 3 mg is packaged in 3 ml Type I glass vials with chlorobutyl rubber stoppers, and aluminum seals with plastic flip-off caps. The vials are stored in refrigerator (2 - 8°C) and protected from light. Metreleptin for injection is a sterile, white, solid lyophilised cake.\n\nPrior to patient use, the content of a vial is reconstituted with 0.6 ml of water for injection for a final formulation of 10 millimolar (mM) glutamic acid, 2% glycine, 1% sucrose, 0.01% polysorbate 20, potential hydrogen (pH) 4.25. The resulting solution is administered by subcutaneous injection."},{"type":"DRUG","name":"Sodium chloride","description":"The placebo will consist of sterile 0.9% saline (Sodium chloride), drawn up from a 10 ml i.v. vials. The placebo will be administered as an subcutaneous injection in an identical procedure as the metreleptin verum."}],"primaryOutcomes":[{"measure":"Clinician-rated depression on the 17 point Hamilton Depression Scale (HAMD-17) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"HAMD-17 is a semi-structured interview and consists of 17 items assessing symptoms of depression from the perspective of the clinician. Possible scores range from 0 (no depressive symptom) to 4 (strong depressive symptom). The higher the total score, the more severe the depressive symptoms.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Body weight status in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"Body weight status will be indicated by weight in kilograms (kg).","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"}],"secondaryOutcomes":[{"measure":"Subjective depression by the Beck Depression Inventory-II (BDI-II) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"The Beck Depression Inventory-II is a self-report rating inventory that measures characteristic attitudes and symptoms of depression with 21 items, ranging from 0 (no depressive symptoms) to 3 (strong depressive symptoms). The higher the total score, the more severe the depressive symptoms.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Functional brain connectivity in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"For assessment of intrinsic functional connectivity in the brain, functional MRI images will be acquired for each patient. A region-of-interest analysis and calculating correlations between any pair of two brain regions, obtaining a connectivity matrix, will be done.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Anorexia Nervosa psychopathology assessed by the Eating Disorders Examination Questionnaire (EDE-Q) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"The Eating Disorders Examination Questionnaire (EDE-Q) is the self-report version of the Eating Disorder Examination (EDE). The 22 items on the four subscales of restraint, eating concern, weight concern, and shape concern are used to assess eating disorder-specific characteristics in their current manifestations during the last 28 days. 7-point rating scales are used to assess frequencies from 0 (characteristic was not present) to 6 (characteristic was present every day or to an extreme degree). Six further, non-scale-forming items also measure the frequency of diagnostically relevant core behaviors over the last 28 days. The EDE-Q is evaluated by calculating subscale mean values for the Restraint, Eating Concern, Weight Concern and Shape Concern subscales and a total score. At Baseline, Post Treatment and intermediate measurements, the instruction of EDE-Q will be modified to refer to a shortened shortened observation time (last week).","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"External rated hyperkinesia assessed by the Structured Inventory for Anorexic and Bulimic Eating Disorders (SIAB, item 42) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"Hyperkinesia will be assessed with only one item (item 42) from the Structured Inventory for Anorexic and Bulimic Eating Disorders (SIAB). This Inventory is used to record the entire spectrum of eating disorder symptoms. Item 42 assesses excessive physical exercise ranging from 0 (no physical exercise) to 4 (very frequent physical exercise).","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Subjective hyperkinesia assessed by the Exercise and Eating Disorders Questionnaire (EED) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"The Exercise and Eating Disorders Questionnaire (EED) is a clinically derived, self-report questionnaire. 19 items are used to assess compulsive exercise among eating disorder patients. The 6-point rating scale is used to assess the frequencies (never, rare, sometimes, often, mostly, always) during the last 4 weeks. A higher total score indicates a stronger manifestation of compulsive exercises.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Autism symptoms assessed by the Autism-Spectrum Quotient-short version (AQ-k) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"The Autism-Spectrum Quotient-short version (AQ-k) is a self-assessment tool for screening for autistic disorder. The 10 items represent autistic symptoms and a 4-point response scale is used to assess the agreement (complete agreement, agree more, rather disagree, complete disagreement) to those.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Patient's quality of life by items 1, 2, 5, 6, 7, 10, 17, 19, 20, and 22 from the WHO Quality of Life Questionnaire (WHOQOL-BREF) in the metreleptin-assisted therapy group compared to placebo-therapy between Baseline, Post Treatment and 5 weeks Follow Up","description":"The WHO Quality of Life Questionnaire (WHOQOL-BREF) with 26 items is a short form of the WHOQOL-100 and is an instrument for recording subjective quality of life. Items 1, 2, 5, 6, 7, 10, 17, 19, 20, and 22 will be used, ranging from 1 (very dissatisfied/ no agreement) to 5 (very satisfied/fully agreement). A higher total score indicates a increased quality of life.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Visual Analog Scale (VAS) about key Anorexia Nervosa and depression symptoms in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"10 items assessing hunger, repetitive thought of food, fear of weight gain, drive for activity, inner tension, feeling full, nausea, feeling fat, depressed mood and feeling tired on a 10-point response scale ranging from 1 (not pronounced symptom) to 10 (strongly pronounced symptom).","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Social interaction by the Liebowitz Social Anxiety Scale (LSAS) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"The Liebowitz Social Anxiety Scale is a clinician-administered assessment that measures the fear and avoidance associated with social anxiety. Item 2,3,4,5,8,10,11,12,15 and 19 will be rated on the response scale for avoidance behavior from 1 (never) to 4 (almost always). Higher scores indicating greater severity of social anxiety.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"},{"measure":"Anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS-D) in the metreleptin-assisted therapy group compared to placebo-therapy group between Baseline, Post Treatment and 5 weeks Follow Up","description":"Anhedonia will be assessed with the german version of the Snaith-Hamilton Pleasure Scale (SHAPS-D) that assesses self-reported anhedonia in psychiatric patients. The respective degree of consent regarding the 14 items on the questionnaire will be rated on a bipolar four-point response scale. For the evaluation, each disagree response ('disagree' or 'strongly disagree') is given 1 point and each agree response is given 0 points. By adding up the points, a higher value indicates a greater degree of anhedonia.","timeFrame":"Baseline (day -1), Post Treatment (day 14) and after 5 weeks Follow Up (day 49)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06305182"},{"nctId":"NCT06548100","title":"A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching From Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD)","officialTitle":"A Single-Arm, Open-Label, Safety Study in Patients With Generalized Lipodystrophy Switching From Metreleptin to Mibavademab, A Leptin Receptor Agonist Antibody","summary":"This study is researching an experimental drug called mibavademab. The study is focused on participants with GLD who have been on metreleptin treatment for at least 6 months with no change in dose for the last 3 months.\n\nThe aim of the study is to see how safe and tolerable mibavademab is when switching from treatment with metreleptin.\n\nThe study is looking at several other research questions, including:\n\n* What side effects may happen from taking mibavademab\n* How much mibavademab is in the blood at different times\n* Whether the body makes antibodies against mibavademab (which could make mibavademab less effective or could lead to side effects)","detailedDescription":null,"peptideSlugs":["metreleptin"],"peptideNames":["Metreleptin"],"conditions":["Generalized Lipodystrophy"],"keywords":["Congenital or acquired generalized lipodystrophy","Leptin deficiency","Loss of subcutaneous tissue","Nutritional deprivation","Severe metabolic derangements","Severe diabetes mellitus","Hypertriglyceridemia","Berardinelli-Seip Syndrome","Lawrence Syndrome","Severe Insulin Resistance"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Regeneron","slug":"regeneron","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":9,"dates":{"start":"2024-12-16","primaryCompletion":"2026-07-09","completion":"2026-07-09","firstPosted":"2024-08-12","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"National Institutes of Health","status":null,"city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026},{"facility":"University of Michigan","status":null,"city":"Ann Arbor","state":"Michigan","country":"United States","latitude":42.27756,"longitude":-83.74088}],"eligibility":{"criteria":"Key Inclusion Criteria:\n\n1. Diagnosis of congenital or acquired GLD as defined by Multi-Society Practice Guidelines\n2. Treatment with metreleptin for ≥6 months at time of screening at a stable dose, defined as no change in dose within the last 3 months prior to screening\n3. Generally stable diet (based on participant's recall) and stable medication regimen for diabetes and/or dyslipidemia (in addition to metreleptin), for the last 3 months prior to screening\n4. Willing and able to comply with clinic visits and study-related procedures. Participants who are unable/unwilling to self-inject, but are willing to have a capable caregiver inject, are considered eligible\n5. Willing and able to provide, or have the treating physician provide, values of HbA1c and fasting triglycerides from at least 6 months prior to screening, as defined in the protocol\n\nKey Exclusion Criteria:\n\n1. Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit\n2. Current chronic treatment with high-dose corticosteroids, as defined in the protocol\n3. Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit except for fully treated basal cell or squamous epithelial cell carcinomas of the skin or carcinoma in situ of the cervix or anus\n4. Estimated glomerular filtration rate (GFR) of \\<30 mL/min/1.73 m\\^2 based on chronic kidney disease epidemiology collaboration (CKD-EPI)/Schwartz equation at screening. Assessment can be repeated once\n5. History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, transient ischemic attack, unstable angina, percutaneous or surgical revascularization procedure, or intracardiac device placement within 3 months before the screening visit, as defined in the protocol\n6. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study, as defined in the protocol\n\nNOTE: Other protocol-defined inclusion / exclusion criteria apply","minimumAge":"2 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"mibavademab","description":"Administered by intravenous (IV) infusion followed by subcutaneous (SC) injection"}],"primaryOutcomes":[{"measure":"Incidence of treatment-emergent adverse events (TEAEs)","description":null,"timeFrame":"Up to week 68"},{"measure":"Severity of TEAEs","description":null,"timeFrame":"Up to week 68"}],"secondaryOutcomes":[{"measure":"Change in Hemoglobin A1c (HbA1c)","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Occurrence of HbA1c <7%","description":null,"timeFrame":"Week 20 and week 52"},{"measure":"Occurrence of HbA1c <6.5%","description":null,"timeFrame":"Week 20 and week 52"},{"measure":"Occurrence of requiring therapy with insulin in participants treated with mibavademab","description":null,"timeFrame":"Week 20 and week 52"},{"measure":"Change in total insulin dose","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Change in fasting plasma glucose","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Percent change in fasting triglycerides","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Occurrence of fasting triglycerides <500 mg/dL in participants treated with mibavademab","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Occurrence of fasting triglycerides <200 mg/dL in participants treated with mibavademab","description":null,"timeFrame":"Baseline, week 20 and week 52"},{"measure":"Occurrence of fasting triglycerides <150 mg/dL in participants treated with mibavademab","description":null,"timeFrame":"Baseline, week 20 and week 52"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06548100"},{"nctId":"NCT07018804","title":"Mechanisms and Targeted Therapy of Airway Basal Cell Dysfunction in Bronchiolitis Obliterans Syndrome","officialTitle":"Analysis of the Pathogenic Mechanism of Abnormal Airway Basal Cell Function in Bronchiolitis Obliterans Syndrome and Research on Targeted Treatment Strategies","summary":"This experimental study aims to investigate the pathogenesis of bronchiolitis obliterans syndrome (BOS) and provide a basis for clinical diagnosis and treatment. The core research question is: whether there is a causal relationship between stem cell dysfunction induced by the inflammatory microenvironment and airway injury repair during the pathological process of BOS? Researchers will collect alveolar lavage fluid specimens from participants and healthy individuals to isolate distal small airway stem cells for subsequent scientific research and comparative analysis, thereby revealing the pathological mechanisms of BOS, exploring precise intervention targets, and developing innovative therapeutic strategies to improve patient prognosis, long-term survival rates, and quality of life.","detailedDescription":"The purpose of this experimental study is to explore the role of airway basal cells in the development of bronchiolitis obliterans syndrome (BOS) and develop potential therapeutic strategies. The main question it aims to answer is: How do the functional abnormalities of airway basal cells (BCs) affect the progression of BOS and what are the underlying molecular mechanisms? Researchers will collect epithelial mucosal tissues from diseased and relatively healthy lung regions of BOS patients through bronchoscopic brushing, and simultaneously gather alveolar lavage fluid specimens when possible. Specimens from healthy volunteers with no obvious airway abnormalities will be used as controls. After that, BCs will be isolated from these specimens. The isolated BCs will be cultured and their molecular characteristics will be identified using immunofluorescence staining to detect the expression of BCs markers such as p63 and Krt5.\n\nSubsequently, single - cell clone libraries will be established by flow cytometry cell fluorescence sorting (FACS) technology. Multiple aspects of the cells' functions will be evaluated, including self - renewal ability by detecting the expression of the proliferation marker Ki67 through immunofluorescence and CCK8 assay, and differentiation ability by analyzing the cell types and proportions in the differentiation structures of in vitro air - liquid interface (ALI) culture for 21 days and in vivo differentiation in severe combined immunodeficiency (NSG) mice for 28 days using Real - time PCR and immunofluorescence techniques.\n\nIn addition, multi - omics sequencing technologies, such as RNA - seq, ATAC - seq, and CUT\\&Tag, will be employed to explore the molecular mechanisms of BCs' functional abnormalities. Stable interference cell lines will be established using CRISPR - Cas9 technology to verify the functions of potential target genes. A ferret BOS model will be constructed, and BCs transplantation experiments will be carried out in ferrets. By observing and analyzing the survival rate, body weight, CT images, and lung tissue pathology of ferrets, the preventive and therapeutic effects of BCs on BOS will be evaluated.\n\nBy clarifying the role of BCs in BOS, this study aims to reveal the underlying pathological mechanisms, explore potential intervention targets, and develop novel treatment approaches. These efforts are expected to improve the prognosis of BOS patients, reduce the incidence and mortality rates, and enhance the overall quality of life for those affected by this life - threatening respiratory disorder.","peptideSlugs":["sincalide"],"peptideNames":["Sincalide"],"conditions":["Bronchiolitis Obliterans Syndrome (BOS)"],"keywords":["Bronchiolitis Obliterans Syndrome","Airway epithelium","Airway basal cells","Inflammatory response"],"conditionGroups":[{"slug":"inflammation","label":"Inflammation"}],"sponsor":{"name":"Haikou Affiliated Hospital of Central South University Xiangya School of Medicine","slug":"haikou-affiliated-hospital-of-central-south-university-xiangya-school-of-medicine","class":"OTHER"},"collaborators":[],"status":{"raw":"WITHDRAWN","group":"withdrawn","label":"Withdrawn"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":0,"dates":{"start":"2026-07-26","primaryCompletion":"2027-06-30","completion":"2028-06-30","firstPosted":"2025-06-12","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":1,"countries":["China"],"locations":[{"facility":"Haikou Affiliated Hospital of Central South University Xiangya School of Medicine","status":null,"city":"Haikou","state":"Hainan","country":"China","latitude":20.03421,"longitude":110.34651}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Patients who have received allogeneic hematopoietic stem cell transplantation and are diagnosed with bronchiolitis obliterans syndrome\n\nExclusion Criteria:\n\n* Bronchoscopy consultation is not suitable for patients who are not suitable for bronchoscopy.","minimumAge":null,"maximumAge":null,"sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"PROCEDURE","name":"Bronchoscopic brushing","description":"The collected samples are digested with tissue collagenase for the culture of airway basal cells (BCs)."},{"type":"GENETIC","name":"Single - cell cloning","description":"After primary BCs are expanded in the P1 passage, single-cell cloning libraries are established by planting them into 384-well cell culture plates in a single-cell per well format using a flow chamber cell sorter. Ten samples are selected from the expandable clones for the identification of differentiation and proliferation capabilities, while the remaining clones are cryopreserved."},{"type":"GENETIC","name":"Cell function identification","description":"For single-cell samples of each patient, in vitro expansion culture is performed to observe the morphology of cells at each passage and calculate the clonogenic rate. Immunofluorescence technique is used to detect the expression of the cell proliferation marker Ki67, and the proliferation capacity is evaluated by combining with the CCK8 assay. Cells at passages P3-P5 are seeded on the permeable membrane of cell culture inserts at a density of \\\\(10\\^6\\\\) cells/cm², and after 21 days of culture, the differentiated structures are collected. The expression of ciliated cell marker Ace-Tubulin and goblet cell marker MUC5AC is detected to assess the differentiation capacity. Meanwhile, cells are injected subcutaneously into NSG mice at \\\\(10\\^6\\\\) cells/injection site for in vivo differentiation for 28 days, and the differentiated structures are collected for pathological analysis."},{"type":"GENETIC","name":"Identification of local microenvironmental changes","description":"The air-liquid interface (ALI) differentiation culture medium is collected, and cell debris is removed by high-speed centrifugation. The supernatant is then collected to extract proteins. Target proteins are purified via immunoprecipitation or affinity chromatography, followed by desalting and concentration for mass spectrometry analysis to detect inflammatory cytokines and extracellular matrix (ECM). Real-time PCR and Western blot techniques are used to measure the expression levels of epithelial markers, mesenchymal markers, and ECM in cells across all groups, thereby evaluating changes in the local microenvironment around small airways."},{"type":"GENETIC","name":"Gene editing","description":"After plasmid construction, based on gene function, the CRISPR-Cas9-sgRNA (all-in-one) plasmid is transiently transfected into expanded single-cell strains via Nucleofection to knockout the target gene, or the CRISPR-dCas9 fusion-sgRNA plasmid is transiently transfected to activate or inhibit the target gene. After 3-5 days of culture, viable cells are sorted by FACS, and single cells are seeded into 96-well plates for two additional passages of expansion. Samples are collected for Sanger sequencing to screen successfully constructed cell lines."},{"type":"PROCEDURE","name":"Prevention of ferret airway basal cell transplantation","description":"Before surgery, basal cells (BCs) of recipient ferrets are collected by bronchoscopic brushing, followed by in vitro culture and identification. Prior to the onset of BOS, the cells are injected into recipient ferrets via bronchoscopy. Outcomes including ferret survival rate, body weight, CT imaging, and lung tissue pathology are collected to evaluate the preventive effect of BCs on BOS."},{"type":"PROCEDURE","name":"Transplantation treatment of ferret airway basal cells","description":"Stable cell lines with target gene knockdown are established in ferret basal cells (BCs). After ferrets develop bronchiolitis obliterans syndrome (BOS), the constructed cell lines are transplanted into recipient ferrets to validate the therapeutic effect of gene-corrected BCs on the disease."}],"primaryOutcomes":[{"measure":"Ki67 Expression Level in Airway Basal Cells","description":"The percentage of Ki67-positive airway basal cells assessed by immunohistochemistry. Ki67 is a nuclear protein associated with cellular proliferation. Higher Ki67 expression indicates greater proliferative activity. Comparison will be made between patients with bronchiolitis obliterans syndrome and healthy controls to evaluate abnormal self-renewal function of airway basal cells in disease states.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Cell Proliferative Activity Assessed by CCK8 Assay","description":"Optical density (OD) values measured by the CCK8 (Cell Counting Kit-8) assay in cultured airway basal cells. The CCK8 assay measures cell viability and proliferation based on the reduction of WST-8 by dehydrogenases in living cells. Higher OD values indicate greater cell proliferation. Comparison will be made between patients with bronchiolitis obliterans syndrome and healthy controls.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Expression of Ciliated Cell Marker Ace-Tubulin in Air-Liquid Interface (ALI) Differentiation Culture","description":"Immunofluorescence staining intensity of Ace-Tubulin (acetylated α-tubulin), a marker for ciliated cells, in airway basal cells cultured under air-liquid interface (ALI) conditions for 21 days. The staining intensity reflects the degree of ciliated cell differentiation from airway basal cells.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Expression of Goblet Cell Marker MUC5AC in Air-Liquid Interface (ALI) Differentiation Culture","description":"Immunofluorescence staining intensity of MUC5AC, a marker for goblet cells, in airway basal cells cultured under air-liquid interface (ALI) conditions for 21 days. The staining intensity reflects the degree of goblet cell differentiation from airway basal cells.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Expression of Ciliated Cell Marker Ace-Tubulin in NSG Mouse Xenograft Model","description":"Immunofluorescence staining intensity of Ace-Tubulin (acetylated α-tubulin), a marker for ciliated cells, in airway basal cells differentiated in vivo in severe combined immunodeficiency (NSG) mice for 28 days.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Expression of Goblet Cell Marker MUC5AC in NSG Mouse Xenograft Model","description":"Immunofluorescence staining intensity of MUC5AC, a marker for goblet cells, in airway basal cells differentiated in vivo in severe combined immunodeficiency (NSG) mice for 28 days.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Survival Rate of Ferrets After Airway Basal Cell Transplantation","description":"Percentage of ferrets surviving at the end of the 32-week observation period following airway basal cell transplantation. Survival is recorded daily. This indicator evaluates the impact of airway basal cell transplantation on disease progression in the bronchiolitis obliterans syndrome ferret model.","timeFrame":"From enrollment to 32 weeks"},{"measure":"Body Weight Changes in Ferrets After Airway Basal Cell Transplantation","description":"Body weight of ferrets measured at baseline and at regular intervals (weekly) over the 32-week observation period following airway basal cell transplantation. Weight change is calculated as the percentage change from baseline. This indicator reflects the overall health status of ferrets and assists in evaluating the effect of airway basal cell transplantation.","timeFrame":"From enrollment to 32 weeks"}],"secondaryOutcomes":[{"measure":"Expression of Airway Basal Cell Markers p63 and Krt5 by Immunofluorescence","description":"Immunofluorescence staining of transformation protein 63 (p63) and keratin 5 (Krt5), two specific markers for airway basal cells. The percentage of p63-positive and Krt5-positive cells among total cultured cells will be assessed. Positive expression of both markers confirms the identity of cultured cells as airway basal cells, ensuring cell source quality for subsequent experiments.","timeFrame":"From enrollment to 32 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07018804"},{"nctId":"NCT07710430","title":"A Study of Leuprorelin 1-Month (4-Week) Formulation in Children With Central Precocious Puberty","officialTitle":"A Single-Arm, Open-Label, Multicenter, Prospective Clinical Study to Evaluate the Effectiveness and Safety of Leuprorelin 1-Month (4-Week) Formulation Administered for 24 Months in Children With Central Precocious Puberty","summary":"A Single-Arm, Open-Label, Multicenter, Prospective Clinical Study to Evaluate the Effectiveness and Safety of Leuprorelin 1-Month (4-Week) Formulation Administered for 24 Months in Children with Central Precocious Puberty","detailedDescription":null,"peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Central Precocious Puberty"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"LG Chem","slug":"lg-chem","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":43,"dates":{"start":"2026-08-01","primaryCompletion":"2029-08-30","completion":"2030-04-30","firstPosted":"2026-07-17","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":1,"countries":["South Korea"],"locations":[{"facility":"Kangdong Sacred Heart Hospital","status":"RECRUITING","city":"Seoul","state":null,"country":"South Korea","latitude":37.566,"longitude":126.9784}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Tanner stage =\\>2\n2. Girls younger than 9 years old, boys younger than 10 years old\n3. Subjects who are diagnosed with central precocious puberty (CPP)\n\nExclusion Criteria:\n\n1. GnRH-independent precocious puberty, incomplete precocious puberty, progressive brain tumors, pituitary adenoma\n2. Hepatic impairment or abnormal liver function tests at screening\n3. Renal impairment or abnormal renal function at screening\n4. Use of following within 8 weeks prior to screening or during the study: medications affecting gonadotropin or sex hormone, systemic steroids, herbal medications\n5. Use of medications associated with seizures\n6. Requirement for treatments affecting the hypothalamic-pituitary-gonadal axis\n7. History of seizures, epilepsy, cerebrovascular disease, or central nervous system disorders/tumors\n8. Known or suspected malignancy","minimumAge":null,"maximumAge":"10 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Leuprorelin","description":"Leuprorelin will be administered every 4 weeks."}],"primaryOutcomes":[{"measure":"Peak luteinizing hormone (LH) level following gonadotropin-releasing hormone (GnRH) stimulation is < 4 International Units per Liter (IU/L).","description":null,"timeFrame":"24 weeks after treatment initiation"}],"secondaryOutcomes":[{"measure":"Peak LH level following GnRH stimulation is < 4 IU/L at 48, 96wk","description":null,"timeFrame":"48 weeks and 96 weeks after treatment initiation"},{"measure":"Changes from baseline in endocrine function: basal LH in IU/L, follicle-stimulating hormone (FSH) in IU/L, testosterone (T) in nanograms per deciliter (ng/dL), estradiol (E2) in picograms per milliliter (pg/mL)","description":null,"timeFrame":"Up to 96 weeks after treatment initiation"},{"measure":"Changes from baseline in pubertal development: Tanner stage","description":null,"timeFrame":"Up to 96 weeks after treatment initiation"},{"measure":"Changes from baseline in growth related parameters: height in centimeter","description":null,"timeFrame":"Up to 96 weeks after treatment initiation"},{"measure":"Changes from baseline in growth related parameters: weight in kilograms","description":null,"timeFrame":"Up to 96 weeks after treatment initiation"},{"measure":"Safety: Number of participants with treatment-related adverse events as assessed by the investigator","description":null,"timeFrame":"Up to 96 weeks after treatment initiation"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07710430"},{"nctId":"NCT07732738","title":"Bariatric Surgery Combined With GLP-1RA: A Multicenter Study.","officialTitle":"The Efficacy and Safety of Bariatric Surgery Combined With GLP-1 Receptor Agonists for Patients With Obesity: A Prospective, Multicenter Cohort Study","summary":"Obese patients exhibit considerable heterogeneity and complex comorbidities, making long-term effective management challenging with single therapies. While bariatric surgery remains the most effective weight-loss intervention, postoperative weight regain and metabolic deterioration require attention. GLP-1 RAs offer distinct advantages for weight and metabolic improvement, and their combined application with surgery may yield synergistic benefits.\n\nGiven the lack of multi-regional validation in China's diverse population, this multicenter study aims to confirm the real-world effectiveness and generalizability of bariatric surgery plus GLP-1RA across distinct regional cohorts.","detailedDescription":"\"bariatric surgery is guideline-recommended as an effective obesity treatment. Substantial evidence demonstrates its ability to significantly reduce weight, improve comorbidities like type 2 diabetes (T2DM) and dyslipidemia, and lower cardiovascular risk. However, the significant heterogeneity and complex comorbidity profiles among obese patients challenge long-term effective management with single therapeutic approaches. While currently the most effective weight-loss intervention, bariatric surgery requires attention to issues such as postoperative weight regain and metabolic deterioration.\n\nIn parallel, Glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated significant efficacy in obesity management. Agents like semaglutide promote weight loss and metabolic improvement through mechanisms including insulin secretion promotion, appetite suppression, delayed gastric emptying, and enhanced satiety.\n\nPrevious single-center studies have confirmed the efficacy of this combination therapy. However, given China's vast geographic and ethnic diversity, it remains unclear whether these findings are generalizable to broader populations. This multicenter study is therefore designed to assess the real-world effectiveness and generalizability of bariatric surgery plus GLP-1RA across distinct regional cohorts in China.","peptideSlugs":["semaglutide","glucagon"],"peptideNames":["Semaglutide","Glucagon"],"conditions":["Obesity"],"keywords":["obesity","Glucagon-Like Peptide-1 Receptor Agonist","Bariatric Surgery","multicenter"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"China-Japan Friendship Hospital","slug":"china-japan-friendship-hospital","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":400,"dates":{"start":"2025-01-01","primaryCompletion":"2027-12-30","completion":"2027-12-30","firstPosted":"2026-07-29","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":7,"countries":["China"],"locations":[{"facility":"Xingtai Ninth Hospital","status":"RECRUITING","city":"Xingtai","state":"Hebei","country":"China","latitude":37.06217,"longitude":114.49272},{"facility":"Zhengzhou Central Hospita","status":"RECRUITING","city":"Zhengzhou","state":"Henan","country":"China","latitude":34.75778,"longitude":113.64861},{"facility":"The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology","status":"RECRUITING","city":"Baotou","state":"Inner Mongolia","country":"China","latitude":40.6516,"longitude":109.84389},{"facility":"The Second Hospital, Cheeloo College of Medicine, Shandong University","status":"RECRUITING","city":"Jinan","state":"Shandong","country":"China","latitude":36.66833,"longitude":116.99722},{"facility":"Sinopharm Tongmei General Hospital","status":"RECRUITING","city":"Datong","state":"Shanxi","country":"China","latitude":40.09361,"longitude":113.29139},{"facility":"The First People Hospital Of Yunnan Province","status":"RECRUITING","city":"Kunming","state":"Yunnan","country":"China","latitude":25.03889,"longitude":102.71833},{"facility":"China-Japan Friendship Hospital","status":"RECRUITING","city":"Beijing","state":null,"country":"China","latitude":39.9075,"longitude":116.39723}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Primary metabolic surgery candidates: Patients undergoing initial laparoscopic sleeve gastrectomy (LSG).\n2. obesity:BMI ≥27.5 kg/m².\n3. Metabolic comorbidities: Diagnosis of metabolic syndrome or type 2 diabetes mellitus (T2DM) meeting standard criteria.\n4. Age range: 16-70 years (inclusive).\n5. Informed consent: Willing participation with documented consent.\n\nExclusion Criteria:\n\n1. Recent GLP-1RA use: Treatment with GLP-1 receptor agonists within 6 months preoperatively.\n2. Prior bariatric surgery: History of any metabolic/bariatric surgical procedure.\n3. Postoperative complications: Requiring reoperation for severe complications (e.g., hemorrhage, anastomotic leak).\n4. Non-indicated candidates: Patients not meeting standard bariatric surgery indications.\n5. Significant comorbidities:\n\nAdvanced hepatic/renal dysfunction (Child-Pugh C or eGFR \\<30 mL/min/1.73m²) Active malignancy (except non-melanoma skin cancers) Autoimmune disorders requiring immunosuppression Uncontrolled psychiatric conditions (e.g., active psychosis, severe depression)","minimumAge":"16 Years","maximumAge":"70 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"COMBINATION_PRODUCT","name":"BS-GLP1RA group","description":"1.Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2.In addition to laparoscopic sleeve gastrectomy and postoperative basic nutritional counseling,the intervention group received subcutaneous semaglutide injections from 1 to 6 months postoperatively.The specific protocol was as follows:In the intervention group, semaglutide treatment was initiated at 1 month after LSG. The starting dose was 0.25 mg per week and was subsequently titrated up based on individual patient response to a maximum maintenance dose of 2.4 mg per week. The treatment continued until the completion of the 6-month postoperative period."},{"type":"PROCEDURE","name":"BS group","description":"1.Basic Treatment Measures Within 0-30 days after sleeve gastrectomy, all patients received very low-calorie enteral nutrition powder (100 kcal/day). From 30 to 90 days post-surgery, a low-energy diet (400 kcal/day) was provided. Beyond 90 days post-surgery, a calorie-restricted diet was implemented (1,500 kcal/day for men and 1,200 kcal/day for women). 2.Observation Group: Received only basic nutritional recommendation interventions after surgery."}],"primaryOutcomes":[{"measure":"the Percentage of weight loss","description":null,"timeFrame":"1 year"}],"secondaryOutcomes":[{"measure":"Weight in kilograms","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Waist circumference in centimeters","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Serum creatinine","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Glomerular filtration rate","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Fasting blood glucose","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Postprandial 2-hour blood glucose","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"HbA1c","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Total cholesterol","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"Low-Density Lipoprotein(LDL)","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."},{"measure":"High-Density Lipoprotein(HDL)","description":null,"timeFrame":"Immediately postoperatively (Day 0), and at 1, 3, 6, and 12 months postoperatively."}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07732738"},{"nctId":"NCT07734792","title":"Tirzepatide in Thrombectomy-Treated Acute Ischemic Stroke: A Randomized Trial","officialTitle":"Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy: A Multicenter, Randomized, Controlled, Blinded Outcome Assessment Trial","summary":"Acute ischemic stroke caused by blockage of a large artery in the brain is one of the leading causes of death and long-term disability worldwide. For patients with this type of stroke, endovascular thrombectomy (EVT), a procedure that removes the blood clot and restores blood flow to the brain, has become the standard treatment. However, even when blood flow is successfully restored, many patients continue to experience disability because of ongoing brain injury caused by inflammation, oxidative stress, and damage to brain cells after the stroke.\n\nThis study aims to evaluate whether tirzepatide, a medication that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) pathways, can improve recovery in patients with acute ischemic stroke caused by large vessel occlusion who receive thrombectomy. Tirzepatide is currently approved for the treatment of conditions such as type 2 diabetes and obesity. Previous studies have shown that tirzepatide can improve blood sugar control, reduce body weight, and provide beneficial effects on cardiovascular health. Laboratory studies and early clinical evidence suggest that medications targeting GLP-1 and GIP pathways may also have protective effects on the brain by reducing inflammation, protecting brain cells, improving blood vessel function, and supporting recovery after stroke.\n\nIn this study, eligible patients with acute ischemic stroke caused by blockage of a major brain artery will be randomly assigned to receive either tirzepatide plus standard stroke care or standard stroke care alone. Participants will receive two subcutaneous injections of tirzepatide: the first dose before the thrombectomy procedure and the second dose 7 days after the procedure. The study will include multiple hospitals and will use independent assessment of outcomes to ensure reliable evaluation of treatment effects.\n\nThe primary purpose of this study is to determine whether early treatment with tirzepatide can improve functional recovery 90 days after stroke, measured by the patient's ability to perform daily activities and live independently. The study will also evaluate whether tirzepatide is safe in patients with acute ischemic stroke by monitoring adverse events, complications, and other clinical outcomes.\n\nThe findings from this study may provide important evidence for a new treatment approach to improve recovery after thrombectomy and reduce disability among patients with severe ischemic stroke.","detailedDescription":"1.1 Stroke Burden Approximately 2.4 million new stroke cases occur annually in China, resulting in about 1.1 million deaths each year. More than 11 million people are currently living with stroke, and the incidence, prevalence, and mortality rates continue to rise, with an increasing trend toward younger age groups. Stroke has become the leading cause of death and disability in China, imposing a substantial burden on patients, families, and society as a whole.\n\nAmong all stroke subtypes, acute ischemic stroke (AIS) accounts for approximately 70%-80% of cases. Patients with concomitant large vessel occlusion (LVO) experience the most severe neurological deficits. Although some patients are eligible for intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA), only 26.5% achieved functional independence at 90 days, while the 90-day mortality rate remains as high as 18.9%, making AIS-LVO one of the greatest challenges in stroke management.\n\n1.2 Endovascular thrombectomy in patients with large vessel occlusion The cornerstone of treatment for acute ischemic stroke with large vessel occlusion (AIS-LVO) is rapid recanalization of the occluded artery to salvage the ischemic penumbra. Since 2015, five landmark randomized controlled trials (RCTs), including MR CLEAN, EXTEND-IA, and SWIFT PRIME, published in The New England Journal of Medicine, have demonstrated the efficacy of endovascular thrombectomy (EVT) in patients with AIS-LVO, representing a revolutionary breakthrough in stroke care.\n\nSubsequently, a pooled meta-analysis published in The Lancet in 2016 showed that EVT achieved a 90-day favorable functional outcome rate of 46.0%, representing a 2.71-fold increase compared with standard medical therapy, further confirming the substantial clinical benefit of thrombectomy.\n\nThe DAWN and DEFUSE 3 trials further extended the EVT treatment window to 24 hours after symptom onset. These studies demonstrated that, among carefully selected patients with salvageable ischemic penumbra identified by advanced imaging, EVT significantly improved clinical outcomes even when performed 6-24 hours after stroke onset. More recently, the BAOCHE and ATTENTION trials extended the proven benefits of EVT to posterior circulation stroke. Consequently, EVT has received the highest level of recommendation in international stroke guidelines.\n\nTo promote stroke prevention and treatment, the National Health Commission of China established the National Stroke Prevention and Control Committee, aiming to advance and expand access to evidence-based stroke interventions, including EVT. Early thrombectomy during the acute phase of stroke plays a critical role in reducing disability and mortality, thereby alleviating the societal burden of stroke.\n\n1.3 Factors influencing outcomes after reperfusion therapy Although approximately 90% of patients achieve successful reperfusion (mTICI 2c-3) following EVT, only 40%-45% attain favorable functional outcomes at 90 days. Nearly half of patients remain severely disabled or die despite successful recanalization.\n\nRecent studies have identified multiple factors associated with poor outcomes after reperfusion therapy, including advanced age, multiple comorbidities, poor collateral circulation, distal microthrombosis and microvascular dysfunction, stress hyperglycemia, inflammatory responses, oxidative stress, hemorrhagic transformation, and cerebral edema. Therefore, interventions targeting multiple pathophysiological pathways may further improve outcomes following EVT.\n\nSeveral studies have investigated strategies aimed at improving microcirculatory dysfunction, reducing inflammation, and providing neuroprotection before or after thrombectomy. Some of these studies have demonstrated promising neuroprotective effects and improved clinical outcomes.\n\n1.4 Neuroprotective effects of GLP-1/GIP dual receptor agonists after stroke Glucagon-like peptide-1 (GLP-1) receptors are widely expressed in pancreatic β-cells, the heart, vasculature, kidneys, immune cells, and the central nervous system. GLP-1 receptor agonists exert glucose-lowering and metabolic regulatory effects through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, improvement of insulin resistance, suppression of chronic inflammation, modulation of lipid metabolism, and promotion of weight loss.\n\nImportantly, GLP-1 receptor agonists can cross the blood-brain barrier (BBB) and directly act on the central nervous system. Their neuroprotective effects include inhibition of neuronal apoptosis, suppression of neuroinflammation, reduction of oxidative stress, preservation of mitochondrial function, enhancement of synaptic plasticity and cognition, and protection of cerebral vasculature and the neurovascular unit.\n\nExperimental studies using middle cerebral artery occlusion (MCAO) models in diabetic db/db mice have demonstrated that GLP-1 analogues, including exendin-4 and liraglutide, reduce oxidative stress and inflammation, improve cerebral microcirculation, and activate the p-Akt/p-eNOS signaling pathway. Exendin-4 also partially reverses MCAO-induced motor dysfunction, cognitive impairment, and urinary dysfunction.\n\nGlucose-dependent insulinotropic polypeptide (GIP) is another major incretin hormone. GIP receptors are expressed in pancreatic β-cells, adipose tissue, the heart, vascular endothelium, immune cells, and the central nervous system. GIP receptor agonists enhance insulin secretion, promote β-cell survival, improve insulin resistance, reduce chronic inflammation, and facilitate weight control through improved lipid handling and redistribution.\n\nLike GLP-1 receptor agonists, GIP receptor agonists can directly act on the brain, exerting anti-apoptotic, anti-inflammatory, antioxidative, and mitochondrial protective effects while preserving BBB integrity and neurovascular unit function.\n\nGiven these complementary mechanisms, GLP-1/GIP dual receptor agonists simultaneously activate both signaling pathways and may provide synergistic benefits in glycemic control and neuroprotection compared with single-receptor agonists.\n\nA recent preclinical study investigated the role of tirzepatide in repairing BBB injury after ischemic stroke. Using both MCAO mouse models and oxygen-glucose deprivation/reoxygenation (OGD/R) cellular models, investigators demonstrated that tirzepatide improved neurological function, reduced BBB permeability, and increased expression of the tight-junction protein Claudin-1. Mechanistic analyses suggested that these effects were mediated through activation of the C/EBP-α/Claudin-1 signaling pathway, thereby maintaining BBB integrity.\n\nAccumulating evidence indicates that GLP-1 receptor agonists have become first-line glucose-lowering agents with benefits extending beyond glycemic control. These benefits include substantial weight loss, reduced risks of coronary heart disease and stroke, and lower rates of heart failure hospitalization. Clinical studies further suggest that GLP-1/GIP dual receptor agonists achieve cardiovascular outcomes comparable to those of GLP-1 receptor agonists while providing superior glycemic control and weight reduction.\n\nBBB disruption, hyperglycemia-related injury, neuroinflammation, oxidative stress, and neuronal apoptosis are recognized as major mechanisms underlying secondary brain injury after successful recanalization in AIS-LVO. Both GLP-1 and GIP receptor agonists can cross the BBB and exert multiple neuroprotective effects, including glucose lowering, anti-inflammatory and antioxidative actions, BBB preservation, inhibition of neuronal apoptosis, and enhancement of synaptic plasticity. Moreover, the two pathways may exert synergistic neuroprotective effects.\n\nA recent randomized study involving 140 patients with AIS-LVO compared semaglutide (0.5 mg administered before thrombectomy and during the first postoperative week) with standard care. The semaglutide group achieved a 10% higher rate of excellent functional outcome (mRS 0-1) at 90 days without significant safety concerns. More recently, the GALLOP-2 trial suggested that semaglutide administered before EVT and again on day 7 after thrombectomy increased the proportion of patients achieving an excellent 90-day functional outcome by 15.3% compared with controls. These findings suggest that early administration of a GLP-1/GIP dual receptor agonist, through its comprehensive multi-target neuroprotective mechanisms, may substantially improve outcomes in patients with AIS-LVO following successful reperfusion.\n\nTherefore, there is an urgent need for a randomized controlled trial to evaluate the efficacy and safety of early GLP-1/GIP dual receptor agonist therapy in patients with AIS-LVO after successful recanalization.\n\nTirzepatide, the investigational drug in the present study, is a dual GLP-1/GIP receptor agonist. Multiple high-quality randomized controlled trials have demonstrated that tirzepatide provides glycemic control and weight reduction superior or non-inferior to GLP-1 receptor agonists such as semaglutide, with an excellent safety profile. These findings have been published in leading journals including The New England Journal of Medicine, The Lancet, and JAMA. Tirzepatide is currently approved for the treatment of type 2 diabetes, obesity, and obstructive sleep apnea.\n\nThe SUMMIT trial enrolled 731 obese patients (BMI ≥30 kg/m²) with heart failure with preserved ejection fraction (HFpEF), who were randomized to tirzepatide (up to 15 mg weekly) or placebo for at least 52 weeks. Tirzepatide significantly reduced the composite endpoint of cardiovascular death or worsening heart failure (9.9% vs. 15.3%), corresponding to a 38% relative risk reduction.\n\nSimilarly, the SURMOUNT-5 trial randomized 751 adults with obesity but without type 2 diabetes to receive tirzepatide (10 or 15 mg weekly) or semaglutide (1.7 or 2.4 mg weekly) for 72 weeks. Tirzepatide demonstrated superior reductions in bo…","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Acute Ischemic Stroke (AIS)"],"keywords":["acute ischemic stroke","endovascular thrombectomy","large vessel occlusion","tirzepatide","GLP-1/GIP"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"yifang zhu","slug":"yifang-zhu","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2","PHASE3"],"slugs":["phase-2","phase-3"],"labels":["Phase 2","Phase 3"],"label":"Phase 2 / Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":430,"dates":{"start":"2026-08-10","primaryCompletion":"2028-05-31","completion":"2028-07-31","firstPosted":"2026-07-29","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":1,"countries":["China"],"locations":[{"facility":"The Second Afliated Hospital of SooChow University","status":null,"city":"Suzhou","state":"Jiangsu","country":"China","latitude":31.30408,"longitude":120.59538}],"eligibility":{"criteria":"Inclusion Criteria:\n\nParticipants must meet all of the following criteria:\n\n1. Age \\>18 years and ≤80 years;\n2. Acute ischemic stroke with imaging-confirmed anterior large vessel occlusion at:\n\n   * Terminal ICA,\n   * M1 segment of the middle cerebral artery, or\n   * Dominant M2 segment;\n3. NIHSS score between 6 and 25 prior to randomization;\n4. Alberta Stroke Program Early CT Score (ASPECTS) of 6-10 before randomization;\n5. Time from symptom onset (or last known well) to planned endovascular thrombectomy within 24 hours;\n6. Pre-stroke mRS score of 0-1;\n7. Patients presenting within 6 hours of symptom onset are eligible for direct EVT. Patients presenting between 6 and 24 hours after symptom onset must undergo advanced imaging demonstrating a salvageable perfusion mismatch and meet the DEFUSE-3 criteria: an infarct core volume \\<70 mL, a mismatch volume \\>15 mL, and a mismatch ratio \\>1.8;\n8. Written informed consent provided by the participant or a legally authorized representative.\n\nExclusion Criteria:\n\nParticipants meeting any of the following criteria will be excluded:\n\n1. Posterior-circulation large vessel occlusion stroke;\n2. Receipt of intravenous thrombolysis prior to randomization;\n3. Simultaneous bilateral anterior-circulation occlusions or concurrent anterior- and posterior-circulation occlusions;\n4. Intracranial hemorrhage on baseline CT or MRI, including subarachnoid hemorrhage or intracerebral hemorrhage; evidence of large established infarction, defined as:\n\n   * ASPECTS \\<6,\n   * Ischemic core volume ≥70 mL on CTP, or\n   * Infarction involving \\>1/3 of the middle cerebral artery territory;\n5. Active bleeding within the previous month (e.g., gastrointestinal, genitourinary, or retinal hemorrhage), major organ surgery or biopsy within 14 days before stroke onset, or known bleeding diathesis;\n6. Refractory hypertension despite treatment, defined as persistent systolic blood pressure \\>180 mmHg or diastolic blood pressure \\>110 mmHg;\n7. Severe hepatic or renal impairment, including:\n\n   * Estimated glomerular filtration rate (eGFR) \\<30 mL/min/1.73 m²,\n   * Serum creatinine \\>200 μmol/L,\n   * Child-Pugh Class C or higher liver disease,\n   * Recurrent unexplained hypoglycemia;\n8. Blood glucose \\<2.7 mmol/L or \\>22.2 mmol/L; platelet count \\<80 × 10⁹/L; or international normalized ratio (INR) \\>1.7;\n9. Previous use of GLP-1 receptor agonists or GIP receptor agonists, or known hypersensitivity to these agents;\n10. Personal or family history of medullary thyroid carcinoma (MTC) or diagnosis of Multiple Endocrine Neoplasia Type 2 (MEN2);\n11. History of severe anxiety or depression prior to stroke onset;\n12. Severe underlying disease with life expectancy \\<1 year, such as advanced malignancy;\n13. Pregnancy or breastfeeding;\n14. Participation in another clinical trial.","minimumAge":"19 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Participants will receive two subcutaneous injections of tirzepatide (5 mg each): the first administered before EVT and the second administered 7 days after EVT, in addition to standard medical care"},{"type":"OTHER","name":"Standard Medical Care (SMC)","description":"Participants will receive EVT and standard medical care without tirzepatide."}],"primaryOutcomes":[{"measure":"The primary efficacy outcome: Proportion of patients achieving an excellent functional outcome","description":"A excellent functional outcome is defined as modified Rankin Scale (mRS) score of 0-1 at 90 days. The Modified Rankin Scale ranges from 0 to 6, where 0 indicates no symptoms, 1 indicates symptoms without significant disability, 2 indicates slight disability, 3 indicates moderate disability, 4 indicates moderately severe disability, 5 indicates severe disability, and 6 indicates death. Higher scores indicate worse functional outcomes.","timeFrame":"90 ± 7 days after randomization"},{"measure":"The primary safety outcome: All-cause mortality","description":"death from any cause within 90 days","timeFrame":"90 ± 7 days"}],"secondaryOutcomes":[{"measure":"The secondary efficacy outcome: Distribution of mRS scores at 90 days after randomization","description":"Ordinal Modified Rankin Scale (mRS) analysis. The Modified Rankin Scale ranges from 0 to 6, where 0 indicates no symptoms, 1 indicates symptoms without significant disability, 2 indicates slight disability, 3 indicates moderate disability, 4 indicates moderately severe disability, 5 indicates severe disability, and 6 indicates death. Higher scores indicate worse functional outcomes.","timeFrame":"90 ± 7 days"},{"measure":"The secondary efficacy outcome: Proportion of patients achieving an good functional outcome","description":"A good functional outcome is defined as an Modified Rankin Scale (mRS) 0-2 at 90 days after randomization.","timeFrame":"90 ± 7 days"},{"measure":"The secondary safety outcome: Symptomatic intracranial hemorrhage (sICH)","description":"defined by the Heidelberg Bleeding Classification within 48 hours after thrombectomy","timeFrame":"within 48 hours after thrombectomy"}],"publications":[{"pmid":"40886075","citation":"Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092."},{"pmid":"34647404","citation":"Furihata K, Mimura H, Urva S, Oura T, Ohwaki K, Imaoka T. A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes. Diabetes Obes Metab. 2022 Feb;24(2):239-246. doi: 10.1111/dom.14572. Epub 2021 Nov 18."},{"pmid":"41392086","citation":"Wang H, Ko H, Leung TW, Huang J, Sai J, Liang Y, Li H, Zhang J, Cao Q, Zang W, Li Y, Ma SH, Lui WT, Choi J, Chan C, Wong J, Kwok AJ, Ma K, Fan F, Chan A, Ip V, Leung H, Soo Y, Wong KT, Lai B, Chu CM, Leung HS, Hui A, Cheung T, Abrigo J, Li SH, Chan L, Yeung J, Pan S, Yip T, Lui LT, Hung T, Tsang SF, Leng X, Lam B, Mok VCT, Chan RHM, Nguyen TN, Hu W, Che F, Ip BY. Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy-a phase 2 randomized trial. Nat Commun. 2025 Dec 14;16(1):11274. doi: 10.1038/s41467-025-66167-z."},{"pmid":"39536238","citation":"Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, Wilding JPH, Perreault L, Zhang S, Battula R, Bunck MC, Ahmad NN, Jouravskaya I; SURMOUNT-1 Investigators. Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med. 2025 Mar 6;392(10):958-971. doi: 10.1056/NEJMoa2410819. Epub 2024 Nov 13."},{"pmid":"34170647","citation":"Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25."},{"pmid":"37952131","citation":"Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornoe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11."},{"pmid":"29402504","citation":"Holscher C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer's and Parkinson's disease models. Neuropharmacology. 2018 Jul 1;136(Pt B):251-259. doi: 10.1016/j.neuropharm.2018.01.040. Epub 2018 Jan 31."},{"pmid":"40702450","citation":"Wang D, Wang J, Li B, Yang S, Guo F, Zheng B, Wang J. Tirzepatide mitigates Stroke-Induced Blood-Brain barrier disruption by modulating Claudin-1 and C/EBP-alpha pathways. Mol Med. 2025 Jul 23;31(1):263. doi: 10.1186/s10020-025-01312-4."},{"pmid":"27296974","citation":"Li PC, Liu LF, Jou MJ, Wang HK. The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice. BMC Neurosci. 2016 Jun 13;17(1):37. doi: 10.1186/s12868-016-0272-9."},{"pmid":"35259929","citation":"Goldenberg RM, Cheng AYY, Fitzpatrick T, Gilbert JD, Verma S, Hopyan JJ. Benefits of GLP-1 (Glucagon-Like Peptide 1) Receptor Agonists for Stroke Reduction in Type 2 Diabetes: A Call to Action for Neurologists. Stroke. 2022 May;53(5):1813-1822. doi: 10.1161/STROKEAHA.121.038151. Epub 2022 Mar 9."},{"pmid":"36372278","citation":"Kopp KO, Glotfelty EJ, Li Y, Greig NH. Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment. Pharmacol Res. 2022 Dec;186:106550. doi: 10.1016/j.phrs.2022.106550. Epub 2022 Nov 11."},{"pmid":"41500725","citation":"Wang C, Gu H, Huo X, Yuan B, Li S, Xu J, Jiang Y, Jing J, Yao X, Li Z, Long F, Ma Z, Zhuang X, Xu L, Jin Y, Huang W, Zhang Y, Wen J, Wang A, Pan Y, Ye W, Yu W, Cheng A, Wang M, Dong Q, Xu A, Wang N, Yang Y, Meng X, Liu L, Zhao X, Li H, Miao Z, Li Z, Wang Y; TASTE-2 investigators. Edaravone dexborneol versus placebo on functional outcomes in patients with acute ischaemic stroke undergoing endovascular thrombectomy (TASTE-2): randomised controlled trial. BMJ. 2026 Jan 7;392:e086850. doi: 10.1136/bmj-2025-086850."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07734792"},{"nctId":"NCT07734870","title":"Tirzepatide for Treatment of CCCA","officialTitle":"Tirzepatide for Treatment of CCCA","summary":"The goal of this pilot clinical trial is to learn if tirzepatide can treat active central centrifugal cicatricial alopecia (CCCA), a type of permanent scarring hair loss, in adults. The main questions it aims to answer are:\n\n* Does tirzepatide improve the symptoms and signs of active CCCA?\n* Does tirzepatide change the activity of genes in the scalp, especially genes related to scarring?\n* Does tirzepatide promote hair regrowth?\n\nParticipants will:\n\n* Inject tirzepatide once a week for 12 months.\n* Visit the clinic for scalp examinations, photographs, and other health assessments.\n* Have scalp biopsies at the beginning of the study and after 6 months of treatment.\n* Have blood tests and other safety monitoring during the study.\n\nThere is no separate comparison group. Researchers will compare each participant's results during treatment with the participant's results at the beginning of the study.","detailedDescription":null,"peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Central Centrifugal Cicatricial Alopecia (CCCA)"],"keywords":["Scarring alopecia","Hair loss","Hair regrowth","Scalp fibrosis","Tirzepatide","Metabolic dysfunction","Insulin Resistance","Gene expression"],"conditionGroups":[{"slug":"hair-loss","label":"Hair loss"}],"sponsor":{"name":"Johns Hopkins University","slug":"johns-hopkins-university","class":"OTHER"},"collaborators":[{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins","slug":"sidney-kimmel-comprehensive-cancer-center-at-johns-hopkins","class":"OTHER"},{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":20,"dates":{"start":"2026-08-23","primaryCompletion":"2028-05-25","completion":"2028-05-25","firstPosted":"2026-07-29","resultsPosted":null,"lastUpdated":"2026-07-29"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"Johns Hopkins Outpatient Center","status":null,"city":"Baltimore","state":"Maryland","country":"United States","latitude":39.29038,"longitude":-76.61219},{"facility":"Medical Pavilion at Howard County","status":null,"city":"Columbia","state":"Maryland","country":"United States","latitude":39.24038,"longitude":-76.83942}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 18 to 80 years.\n* Clinical and/or biopsy-confirmed diagnosis of central centrifugal cicatricial alopecia (CCCA).\n* Active CCCA, defined as a C-CAT disease activity score greater than 1.\n* No treatment for CCCA during the 6 weeks before enrollment.\n* Able and willing to complete the study and follow all study procedures.\n* Managed by a Johns Hopkins dermatologist throughout the study.\n\nExclusion Criteria:\n\n* Currently taking an oral or systemic blood glucose-lowering medication.\n* Currently taking another medication for weight loss.\n* Hemoglobin A1C below 5.4%.\n* Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score below 2.\n* Body mass index below 19 kg/m².\n* Pregnant, breastfeeding, or planning a pregnancy.\n* Personal or family history of medullary thyroid cancer.\n* Personal or family history of multiple endocrine neoplasia type 2.\n* History of chronic kidney disease.\n* History of pancreatitis.\n* History of diabetic retinopathy.\n* Severe gastrointestinal disease.\n* Recent or planned major surgery.\n* Type 1 diabetes.\n* Any other contraindication to tirzepatide.\n* History of keloids or hypertrophic scarring.\n* History of poor wound healing.\n* History of a blood-clotting disorder.\n* Allergy to lidocaine or epinephrine.\n* Known sensitivity to local numbing medication.\n* Any significant medical condition that the investigator believes would make participation unsafe or prevent completion of the study.","minimumAge":"18 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Tirzepatide solution will be self-administered by subcutaneous injection once weekly. Participants will receive 2.5 mg once weekly for the first 4 weeks, followed by 5 mg once weekly for the remainder of the 12-month treatment period. Injection sites will be rotated among the abdomen, thigh, or upper arm."}],"primaryOutcomes":[{"measure":"Change in Central Centrifugal Cicatricial Alopecia Clinical Activity Tool Score","description":"Disease activity will be measured using the Central Centrifugal Cicatricial Alopecia Clinical Activity Tool (C-CAT). The C-CAT assesses disease progression, scalp pain or tenderness, scalp itching, inflammation, and scalp fibrosis. Total scores range from 0 to 10, with higher scores indicating greater disease activity. Scores obtained during treatment will be compared with the baseline score.","timeFrame":"Baseline, 3 months, 6 months"},{"measure":"Change in Scalp Gene-Expression Profiles","description":"Differential messenger RNA expression will be assessed using bulk RNA sequencing of paired scalp biopsies collected at baseline and 6 months of tirzepatide treatment. Differential expression will be defined as at least a two-fold change with an adjusted p-value less than 0.05. Analyses will focus on profibrotic and inflammatory pathways, including transforming growth factor beta, collagens 1, 3, and 6A1, and T-helper 17-related pathways.","timeFrame":"Baseline, 6 months"}],"secondaryOutcomes":[{"measure":"Change in Central Hair Loss Grade","description":"Central scalp hair loss will be evaluated by physician raters using standardized clinical photographs and the Central Hair Loss Grade scale. Scores range from 0 to 5, with higher scores indicating more severe central hair loss. Scores obtained during treatment will be compared with the baseline score.","timeFrame":"Baseline, 3 months, 6 months"},{"measure":"Physician Global Assessment of Change in Hair Loss","description":"Physician raters will compare standardized clinical photographs obtained at months 3 and 6 with baseline photographs. Change in hair loss will be evaluated using a 5-point physician global assessment scale. Score range 0 (None) - 4 (Very severe).","timeFrame":"Baseline, 3 months, 6 months"}],"publications":[{"pmid":"40771443","citation":"Qadri A, Will E, Aguh C. Using Disease Symptomatology to Guide Treatment in Patients with Central Centrifugal Cicatricial Alopecia: Introduction of C-CAT Scoring Tool. Skin Appendage Disord. 2025 Aug;11(4):309-315. doi: 10.1159/000544777. Epub 2025 Feb 20."},{"pmid":"29282458","citation":"Dina Y, Okoye GA, Aguh C. Association of Uterine Leiomyomas With Central Centrifugal Cicatricial Alopecia. JAMA Dermatol. 2018 Feb 1;154(2):213-214. doi: 10.1001/jamadermatol.2017.5163."},{"pmid":"38856224","citation":"Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA, Nikooie A, Bunck MC, Haupt A, Sanyal AJ; SYNERGY-NASH Investigators. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024 Jul 25;391(4):299-310. doi: 10.1056/NEJMoa2401943. Epub 2024 Jun 8."},{"pmid":"39230880","citation":"Bao A, Qadri A, Gadre A, Will E, Collins D, Ahima R, Bordone LA, Aguh C. Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia. JAMA Dermatol. 2024 Nov 1;160(11):1211-1219. doi: 10.1001/jamadermatol.2024.3062."},{"pmid":"33378699","citation":"Tuleta I, Frangogiannis NG. Diabetic fibrosis. Biochim Biophys Acta Mol Basis Dis. 2021 Apr 1;1867(4):166044. doi: 10.1016/j.bbadis.2020.166044. Epub 2020 Dec 28."},{"pmid":"29913259","citation":"Aguh C, Dina Y, Talbot CC Jr, Garza L. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018 Nov;79(5):904-912.e1. doi: 10.1016/j.jaad.2018.05.1257. Epub 2018 Jun 18."},{"pmid":"35007355","citation":"Jamerson TA, Conover Talbot C Jr, Dina Y, Kwatra SG, Garza LA, Aguh C. Gene expression profiling suggests severe, extensive central centrifugal cicatricial alopecia may be both clinically and biologically distinct from limited disease subtypes. Exp Dermatol. 2022 May;31(5):789-793. doi: 10.1111/exd.14524. Epub 2022 Jan 20."},{"pmid":"33609590","citation":"Roche FC, Harris J, Ogunleye T, Taylor SC. Association of type 2 diabetes with central centrifugal cicatricial alopecia: A follow-up study. J Am Acad Dermatol. 2022 Mar;86(3):661-662. doi: 10.1016/j.jaad.2021.02.036. Epub 2021 Feb 18. No abstract available."},{"pmid":"24680004","citation":"Ogunleye TA, McMichael A, Olsen EA. Central centrifugal cicatricial alopecia: what has been achieved, current clues for future research. Dermatol Clin. 2014 Apr;32(2):173-81. doi: 10.1016/j.det.2013.12.005. Epub 2014 Jan 22."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07734870"},{"nctId":"NCT02262806","title":"Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy","officialTitle":"Compassionate Use of Metreleptin in Previously-Treated Patients With Partial Lipodystrophy","summary":"Background:\n\n\\- Partial lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease.\n\nObjective:\n\n\\- To test the safety and effectiveness of metreleptin.\n\nEligibility:\n\n* People age 6 months and older with partial lipodystrophy who\n* have received metreleptin through NIH studies and shown improvement AND\n* cannot get metreleptin other ways.\n\nDesign:\n\n* Participants will come to NIH approximately every 6 months during year one, then every 1 2 years. Financial assistance may be available for travel within the U.S.\n* At visits, participants will get a supply of metreleptin to take home for daily injections, or it can be shipped to them inside the U.S. They will have:\n* plastic catheter placed in an arm vein.\n* blood tests, urine collection, and physical exam.\n* oral glucose tolerance test, drinking a sweet liquid.\n* ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the skin and pictures are taken of the organs.\n* echocardiogram, which takes pictures of the heart with sound waves.\n* Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they breathe is measured.\n* Participants will have up to 3 DEXA scan x-rays per year.\n* Participants may have:\n* annual bone x-rays.\n* liver biopsies every few years. A needle will be inserted into the liver to obtain a small piece. Participants will sign a separate consent for this.\n* Participants must be seen regularly by their local doctors and have blood tests at least every 3-6 months at home.","detailedDescription":"Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue to the rest of the body conveying information about long-term nutritional status. Patients with lipodystrophy have leptin deficiency secondary to lack of adipose tissue. The combination of leptin deficiency and ectopic lipid deposition in patients with lipodystrophy leads to metabolic complications including severe insulin resistance and diabetes, hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. Between 2000 and 2014, the NIDDK IRP conducted an open-label clinical trial of the recombinant human leptin analog, metreleptin, in patients with generalized and partial forms of lipodystrophy. This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. Based on these data, metreleptin was approved by the FDA in February, 2014, for patients with generalized, but not partial, lipodystrophy. Our data have shown, however, that a subgroup of patients with partial lipodystrophy do gain medical benefit from metreleptin.\n\nThe purpose of this study is twofold:\n\n* To provide access to metreleptin to patients with partial lipodystrophy who have previously received and derived benefit from metreleptin through NIH studies (protocols 02-DK-0022 and 13-DK-0057).\n* To continue to collect data on the long-term efficacy of metreleptin in ameliorating the metabolic complications of partial lipodystrophy.\n\nMetreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on body weight and metabolic control. Patients will be seen approximately once per year at NIH for evaluation, and potentially less frequently for those who are medically stable and have difficulty traveling to NIH. Laboratory evaluation will be obtained more frequently by the patient s home providers as clinically indicated. The primary outcomes of the study are improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and bone mineral metabolism, and pituitary and reproductive function.\n\nMetreleptin is supplied by Chiesi USA, Inc. Neither the NIH nor Chiesi USA, Inc. can guarantee that leptin will be available indefinitely and/or after the study ends.","peptideSlugs":["metreleptin"],"peptideNames":["Metreleptin"],"conditions":["Diabetes","Lipodystrophy","Hyperlipidemia"],"keywords":["Lipodystrophy","Leptin","Hypertriglyceridemia","Diabetes"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","slug":"national-institute-of-diabetes-and-digestive-and-kidney-diseases-niddk","class":"NIH"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":29,"dates":{"start":"2014-10-14","primaryCompletion":"2027-07-31","completion":"2027-07-31","firstPosted":"2014-10-13","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institutes of Health Clinical Center","status":null,"city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026}],"eligibility":{"criteria":"* INCLUSION CRITERIA\n* Age greater than or equal to 6 months\n* Partial lipodystrophy (either genetic or acquired)\n* Previously or currently treated with metreleptin under NIH study 02-DK-0022 and/or NIH study 13-DK-0057.\n* Documented metabolic benefit from prior or current metreleptin treatment, defined as one or more of the following:\n\n  * TG reduction greater than or equal to 30% OR\n  * HbA1c reduction greater than or equal to 1% OR\n  * Decrease in insulin requirements greater than or equal to 40% OR\n  * Decrease in episodes of pancreatitis OR\n  * Improvement in steatohepatitis OR\n  * Withdrawal of metreleptin led to marked worsening of metabolic parameters\n\nEXCLUSION CRITERIA\n\n* Availability of metreleptin to the patient either as an approved drug, or through local compassionate use or expanded access programs.\n* Known HIV infection or HIV-associated lipodystrophy.\n* Psychiatric disorder impeding competence or compliance.\n* Any medical condition or medication that will increase risk to the subject.\n* Current alcohol or substance abuse.\n* Subjects who have a known hypersensitivity to E. coli derived proteins.","minimumAge":"6 Months","maximumAge":"98 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Metreleptin","description":"A leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with partial lipodystrophy."}],"primaryOutcomes":[{"measure":"Serum hemoglobin A1C","description":"improvement in lab value","timeFrame":"every 6-12 months"},{"measure":"Serum triglycerides","description":"improvement in lab value","timeFrame":"every 6-12 months"}],"secondaryOutcomes":[],"publications":[{"pmid":"31314093","citation":"Akinci B, Oral EA, Neidert A, Rus D, Cheng WY, Thompson-Leduc P, Cheung HC, Bradt P, Foss de Freitas MC, Montenegro RM, Fernandes VO, Cochran E, Brown RJ. Comorbidities and Survival in Patients With Lipodystrophy: An International Chart Review Study. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5120-5135. doi: 10.1210/jc.2018-02730."},{"pmid":"31194872","citation":"Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of Metreleptin Treatment in Familial Partial Lipodystrophy Due to PPARG vs LMNA Pathogenic Variants. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3068-3076. doi: 10.1210/jc.2018-02787."},{"pmid":"28324110","citation":"Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT02262806"},{"nctId":"NCT04484818","title":"Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) After Surgery for Men With High-Risk Prostate Cancer, The ERADICATE Study","officialTitle":"A Phase III Double Blinded Study of Early Intervention After RADICAl ProstaTEctomy With Androgen Deprivation Therapy With or Without Darolutamide vs. Placebo in Men at Highest Risk of Prostate Cancer Metastasis by Genomic Stratification (ERADICATE)","summary":"This phase III trial compares the effect of adding darolutamide to ADT versus ADT alone after surgery for the treatment of high-risk prostate cancer. ADT reduces testosterone levels in the blood. Testosterone is a hormone made mainly in the testes and is needed to develop and maintain male sex characteristics, such as facial hair, deep voice, and muscle growth. It also plays role in prostate cancer development. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. Giving darolutamide with ADT may work better in eliminating or reducing the size of the cancer and/or prevent it from returning compared to ADT alone in patients with prostate cancer.","detailedDescription":"PRIMARY OBJECTIVE:\n\nI. To determine whether 12 months of androgen deprivation therapy (ADT) and darolutamide improves metastasis-free survival (MFS) compared to 12 months of ADT plus placebo in men with high risk prostate cancer (defined by Cancer of the Prostate Risk Assessment Post-surgical \\[CAPRA-S\\] score \\>= 3 and a high Decipher score (\\>= 0.6) \\[C3+D+\\]) who have undergone radical prostatectomy.\n\nSECONDARY OBJECTIVES:\n\nI. To determine whether 12 months of ADT and darolutamide improves recurrence-free survival (RFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy.\n\nII. To determine whether 12 months of ADT and darolutamide improves event-free survival (EFS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy.\n\nIII. To determine whether 12 months of ADT and darolutamide improves overall survival (OS) compared to 12 months of ADT plus placebo in men with high-risk prostate cancer that have undergone radical prostatectomy.\n\nIV. To determine the rate of testosterone recovery and time to testosterone recovery in each treatment arm.\n\nV. To evaluate the safety and tolerability of ADT and darolutamide.\n\nCORRELATIVE OBJECTIVES FOR EXPLORATORY BIOMARKERS:\n\nI. To discover a novel gene expression signature in the Decipher transcriptome platforms that is predictive of clinical outcome, as defined by the primary and secondary objectives of this study, in response to ADT by intensification with darolutamide versus ADT alone.\n\nII. To assess the prevalence of subclasses of established transcriptome expression signatures and prospectively validate their predictive value for ADT response, these include: (i) androgen (AR) activity (ii) Basal-luminal subtyping based on modified PAM50, and (iii) ADT score.\n\nIII. To assess whether the spectrum of high Decipher scores (0.6-1.0), prostate-specific antigen (PSA) levels at presentation and post-radical prostatectomy (RP) and final pathology variables affect the response and outcome to ADT and darolutamide.\n\nQUALITY OF LIFE (QOL) OBJECTIVES:\n\nI. To compare overall quality of life, measured by Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, at 18 months between the two arms. (Primary) II. To compare the change in overall quality of life, measured by FACT-P total score, from baseline to 18 months between the two arms. (Secondary) III. To compare patient-reported fatigue (Functional Assessment of Chronic Illness Therapy \\[FACIT\\]-Fatigue scores) at 12 months between the two treatment arms. (Secondary) IV. To compare the change in subjective patient-reported cognitive function (FACT-Cognitive \\[Cog\\]) from baseline to 12 months between the treatment arms. (Exploratory) V. To compare subjective patient-reported cognitive function (FACT-Cog scores) at 12 months between the two treatment arms. (Exploratory)\n\nOUTLINE: Patients are randomized to 1 of 2 arms.\n\nARM I: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive a placebo four times daily (QID) for 52 weeks in the absence of disease progression or unacceptable toxicity.\n\nARM II: Patients receive goserelin acetate, leuprolide acetate, or triptorelin via injection every 3 months for 12 months (4 injections), every 4 months for 12 months (3 injections), or every month for 12 months (12 injections) in the absence of disease progression or unacceptable toxicity. Patients also receive darolutamide QID for 52 weeks in the absence of disease progression or unacceptable toxicity.\n\nAfter completion of study treatment, patients are followed up every 3 months for 36 months.","peptideSlugs":["goserelin","triptorelin","leuprolide"],"peptideNames":["Goserelin","Triptorelin","Leuprolide"],"conditions":["Prostate Carcinoma"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"ECOG-ACRIN Cancer Research Group","slug":"ecog-acrin-cancer-research-group","class":"NETWORK"},"collaborators":[{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":27,"dates":{"start":"2021-03-01","primaryCompletion":"2026-06-09","completion":"2028-05-31","firstPosted":"2020-07-24","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":115,"countries":["United States"],"locations":[{"facility":"City of Hope Comprehensive Cancer Center","status":null,"city":"Duarte","state":"California","country":"United States","latitude":34.13945,"longitude":-117.97729},{"facility":"Los Angeles County-USC Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"USC / Norris Comprehensive Cancer Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Stanford Cancer Institute Palo Alto","status":null,"city":"Palo Alto","state":"California","country":"United States","latitude":37.44188,"longitude":-122.14302},{"facility":"VA Palo Alto Health Care System","status":null,"city":"Palo Alto","state":"California","country":"United States","latitude":37.44188,"longitude":-122.14302},{"facility":"City of Hope South Pasadena","status":null,"city":"South Pasadena","state":"California","country":"United States","latitude":34.11612,"longitude":-118.15035},{"facility":"City of Hope Upland","status":null,"city":"Upland","state":"California","country":"United States","latitude":34.09751,"longitude":-117.64839},{"facility":"Hartford Hospital","status":null,"city":"Hartford","state":"Connecticut","country":"United States","latitude":41.76371,"longitude":-72.68509},{"facility":"GenesisCare USA - Lakewood Ranch","status":null,"city":"Lakewood Rch","state":"Florida","country":"United States","latitude":27.3863,"longitude":-82.4332},{"facility":"Mount Sinai Medical Center","status":null,"city":"Miami Beach","state":"Florida","country":"United States","latitude":25.79065,"longitude":-80.13005},{"facility":"GenesisCare USA - Plantation","status":null,"city":"Plantation","state":"Florida","country":"United States","latitude":26.13421,"longitude":-80.23184},{"facility":"Hawaii Cancer Care Inc - Waterfront Plaza","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Queen's Cancer Cenrer - POB I","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Queen's Medical Center","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Straub Clinic and Hospital","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Queen's Cancer Center - Kuakini","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"The Cancer Center of Hawaii-Liliha","status":null,"city":"Honolulu","state":"Hawaii","country":"United States","latitude":21.30694,"longitude":-157.85833},{"facility":"Pali Momi Medical Center","status":null,"city":"‘Aiea","state":"Hawaii","country":"United States","latitude":21.38222,"longitude":-157.93361},{"facility":"Rush - Copley Medical Center","status":null,"city":"Aurora","state":"Illinois","country":"United States","latitude":41.76058,"longitude":-88.32007},{"facility":"Illinois CancerCare-Bloomington","status":null,"city":"Bloomington","state":"Illinois","country":"United States","latitude":40.4842,"longitude":-88.99369},{"facility":"Illinois CancerCare-Canton","status":null,"city":"Canton","state":"Illinois","country":"United States","latitude":40.55809,"longitude":-90.03512},{"facility":"Illinois CancerCare-Carthage","status":null,"city":"Carthage","state":"Illinois","country":"United States","latitude":40.41643,"longitude":-91.13625},{"facility":"Northwestern University","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"University of Chicago Comprehensive Cancer Center","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* PRE-REGISTRATION INCLUSION (STEP 0)\n* Patient must have undergone a radical prostatectomy (RP) and must be registered to step 0 of this study at least 6 weeks after but not more than 16 weeks after their radical prostatectomy\n* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2\n* Patient with a prior or concurrent malignancy within 5 years of registration, whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* For patients with no previous Decipher score: Tumor tissue specimen from prostatectomy must be available and ready to be shipped\n* INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)\n* For patients who have previously had Decipher score performed by Decipher Biosciences, they must have score of \\>= 0.6\n* For patients who did not have a Decipher score previously performed by Decipher Biosciences, they must have had a Decipher score of \\>= 0.6 assessed from the prostatectomy specimen submitted\n* For patients who did not have a Decipher score previously performed by Decipher Biosciences, patients must also have a CAPRA-S score \\>= 3. The CAPRA-S score is calculated by assigning points for PSA in ng/mL, surgical margin status, seminal vesicle invasion, and extra-capsular extension. Lymph node involvement will serve as an exclusion criteria and will not count towards CAPRA-S inclusion score. A CAPRA-S score is not required for patients who had a Decipher score previously performed by Decipher Biosciences\n* Patient must have an undetectable PSA (\\< 0.2ng/mL) obtained within 2 weeks prior to randomization\n* Leukocytes \\>= 3,000/mcL (obtained within 4 weeks prior to registration)\n* Absolute neutrophil count \\>= 1,000/mcL (obtained within 4 weeks prior to registration)\n* Platelets \\>= 75,000/mcL (obtained within 4 weeks prior to registration)\n* Total bilirubin =\\< institutional upper limit of normal (ULN) (obtained within 4 weeks prior to registration)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\< 2.5 x institutional ULN (obtained within 4 weeks prior to registration)\n* Glomerular filtration rate (GFR) \\>= 30 mL/min/1.73 m\\^2 (obtained within 4 weeks prior to registration)\n\nExclusion Criteria:\n\n* PRE-REGISTRATION EXCLUSION (STEP 0)\n* Patient must not have any previous treatment with androgen deprivation therapy (ADT), chemotherapy, or other physician prescribed systemic therapy for treatment of their prostate cancer\n* Patient must not have pathologic evidence of pelvic lymph node involvement\n* Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* EXCLUSION CRITERIA FOR RANDOMIZATION (STEP 1)\n* Patient must not have pre or post-operative radiographic evidence of cancer recurrence or metastasis by abdominal and pelvic imaging (computed tomography \\[CT\\] abdomen/pelvis, whole body magnetic resonance imaging \\[MRI\\], MRI abdomen/pelvis, or equivalent, AND bone scan) which must be done before or after prostatectomy prior to randomization. If pre-operative risk does not indicate a need for bone scan, post-operative Decipher score of \\>= 0.6 indicates increased risk of metastatic disease and may be used to obtain CT abdomen/pelvis and bone scan prior to randomization","minimumAge":"18 Years","maximumAge":null,"sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Darolutamide","description":"Given PO"},{"type":"DRUG","name":"Goserelin Acetate","description":"Given via injection"},{"type":"DRUG","name":"Leuprolide Acetate","description":"Given IV"},{"type":"DRUG","name":"Placebo Administration","description":"Given PO"},{"type":"OTHER","name":"Quality-of-Life Assessment","description":"Ancillary studies"},{"type":"DRUG","name":"Triptorelin","description":"Given via injection"}],"primaryOutcomes":[{"measure":"Metastasis-free survival (MFS)","description":"The primary comparison will be an intention-to-treat analysis of all randomized patients. The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.","timeFrame":"From randomization to development of metastatic disease or death, whichever occurs first, assessed up to 36 months"}],"secondaryOutcomes":[{"measure":"Recurrence-free survival (RFS)","description":"The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.","timeFrame":"From randomization to any of the MFS events, pelvic lymph node recurrence or detectable prostate-specific antigen (PSA) (PSA >= 0.2 ng/mL, confirmed by a second PSA of the same level or higher), whichever occurs first, assessed up to 36 months"},{"measure":"Event-free survival","description":"The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.","timeFrame":"From randomization to any of the RFS events, treatment with salvage radiation therapy with or without systemic therapy, or initiation of systemic therapy for presumed recurrence, whichever occurs first, assessed up to 36 months"},{"measure":"Overall survival","description":"The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.","timeFrame":"From randomization to death by any cause or date last known alive, assessed up to 36 months"},{"measure":"Testosterone recovery rate","description":"Exact binomial confidence intervals will be used to describe the proportions of patients with testosterone recovery in each arm.","timeFrame":"At time of disease progression, assessed up to 36 months"},{"measure":"Time to testosterone recovery","description":"The method of Kaplan and Meier will be used to characterize the time-to-event endpoints, and a logrank test will be used to compare these endpoints across treatments.","timeFrame":"From randomization to a return of serum testosterone level to greater than or equal to lower limit of normal for the testosterone assay, assessed up to 36 months"},{"measure":"Incidence of adverse events","description":"Toxicity will be defined using the Common Terminology Criteria for Adverse Events version 5.0.","timeFrame":"Up to 78 weeks"},{"measure":"Change in quality of life: Functional Assessment of Cancer Therapy (FACT)","description":"Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate, FACT - Cognitive, and Functional Assessment of Chronic Illness Therapy - Fatigue. Fatigue instruments at baseline, 6, 12 and 18 months, and descriptive statistics will be used to characterize quality of life over time in each arm. Each item is answered on a 5-point Likert-type scale, where a value of 0 indicates the statement is not applicable, and a value of 5 indicates the statement is applicable to the respondent. Subgroup analysis will be performed among patients who receive adjuvant radiation therapy and patients who do not receive adjuvant radiation therapy in each arm. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.","timeFrame":"Baseline up to 18 months"},{"measure":"Overall quality of life: Functional Assessment of Cancer Therapy (FACT)","description":"Will be assessed by the Functional Assessment of Cancer Therapy (FACT) - Prostate total score. The total score can range from 0 to 156, where a higher value indicates a better quality of life. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.","timeFrame":"At 18 months"},{"measure":"Change in Functional Assessment of Cancer Therapy (FACT) - Prostate score","description":"A paired t test will be used to compare Functional Assessment of Cancer Therapy (FACT) - Prostate scores at these two time points in each arm. The total score can range from 0 to 156, where a higher value indicates a better quality of life. A two-sample t test will be performed to compare the changes in FACT - Prostate scores from baseline to 18 months between the two arms. Mixed effect models will be constructed as an exploratory analysis to estimate the time profile of quality of life assessments in the two arms and to evaluate treatment-by-time interactions.","timeFrame":"Baseline up to 18 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT04484818"},{"nctId":"NCT05050942","title":"A Trial to Assess Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With GEP-NET","officialTitle":"A Randomized, Multi-center, Open-label, Active-controlled Phase 3 Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot (CAM2029) Versus Octreotide LAR or Lanreotide ATG in Patients With GEP-NET","summary":"The purpose of this study is to compare the effectiveness and safety of CAM2029 to octreotide LAR or lanreotide ATG in patients with advanced, well-differentiated GEP-NET. Patients who experience progressive disease in the randomized part of the study may proceed to an open-label extension part with intensified treatment with CAM2029.","detailedDescription":null,"peptideSlugs":["octreotide","lanreotide"],"peptideNames":["Octreotide","Lanreotide"],"conditions":["Gastro-enteropancreatic Neuroendocrine Tumor"],"keywords":["CAM2029","GEP-NET","Octreotide","SORENTO"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Camurus AB","slug":"camurus-ab","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":332,"dates":{"start":"2021-10-22","primaryCompletion":"2026-11","completion":"2028-11","firstPosted":"2021-09-21","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":86,"countries":["Australia","Belgium","Canada","France","Germany","Hungary","Israel","Italy","Netherlands","Romania","Spain","United States"],"locations":[{"facility":"Mayo Clinic Cancer Center (MCCC) - Phoenix","status":null,"city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"UCLA Ahmanson Biological Imaging Center","status":null,"city":"Santa Monica","state":"California","country":"United States","latitude":34.01949,"longitude":-118.49138},{"facility":"Rocky Mountain Cancer Centers - Denver - Midtown","status":null,"city":"Denver","state":"Colorado","country":"United States","latitude":39.73915,"longitude":-104.9847},{"facility":"Mayo Clinic Hospital - Florida","status":null,"city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"University of Kentucky (UK) - Markey Cancer Center","status":null,"city":"Lexington","state":"Kentucky","country":"United States","latitude":37.98869,"longitude":-84.47772},{"facility":"East Jefferson General Hospital","status":null,"city":"Metairie","state":"Louisiana","country":"United States","latitude":29.98409,"longitude":-90.15285},{"facility":"Dana-Farber Cancer Institute","status":null,"city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977},{"facility":"Mayo Clinic Rochester","status":null,"city":"Rochester","state":"Minnesota","country":"United States","latitude":44.02163,"longitude":-92.4699},{"facility":"Memorial Sloan-Kettering Cancer Center","status":null,"city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Texas Oncology - Austin","status":null,"city":"Austin","state":"Texas","country":"United States","latitude":30.26715,"longitude":-97.74306},{"facility":"Texas Oncology - Dallas","status":null,"city":"Dallas","state":"Texas","country":"United States","latitude":32.78306,"longitude":-96.80667},{"facility":"The University of Texas - MD Anderson Cancer Center","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327},{"facility":"Texas Oncology - McAllen","status":null,"city":"McAllen","state":"Texas","country":"United States","latitude":26.20341,"longitude":-98.23001},{"facility":"Texas Oncology - San Antonio Northeast","status":null,"city":"San Antonio","state":"Texas","country":"United States","latitude":29.42412,"longitude":-98.49363},{"facility":"Huntsman Cancer Institute","status":null,"city":"Salt Lake City","state":"Utah","country":"United States","latitude":40.76078,"longitude":-111.89105},{"facility":"GenesisCare - North Shore","status":null,"city":"Alexandria","state":null,"country":"Australia","latitude":-33.89989,"longitude":151.19951},{"facility":"Fiona Stanley Hospital","status":null,"city":"Murdoch","state":null,"country":"Australia","latitude":-32.06987,"longitude":115.83757},{"facility":"Cliniques Universitaires Saint-Luc","status":null,"city":"Brussels","state":null,"country":"Belgium","latitude":50.85045,"longitude":4.34878},{"facility":"Hôpital Erasme","status":null,"city":"Brussels","state":null,"country":"Belgium","latitude":50.85045,"longitude":4.34878},{"facility":"Antwerp University Hospital","status":null,"city":"Edegem","state":null,"country":"Belgium","latitude":51.15662,"longitude":4.44504},{"facility":"Algemeen Ziekenhuis Maria Middelares","status":null,"city":"Ghent","state":null,"country":"Belgium","latitude":51.05,"longitude":3.71667},{"facility":"AZ Nikolaas","status":null,"city":"Sint-Niklaas","state":null,"country":"Belgium","latitude":51.16509,"longitude":4.1437},{"facility":"London Health Sciences Centre","status":null,"city":"London","state":null,"country":"Canada","latitude":42.98339,"longitude":-81.23304},{"facility":"Centre Hospitalier de l'Universite de Montreal - Notre-Dame Hospital","status":null,"city":"Montreal","state":null,"country":"Canada","latitude":45.50884,"longitude":-73.58781}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Male or female patient ≥18 years old\n* Histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of GEP or presumed GEP origin\n* At least 1 measurable, somatostatin receptor-positive lesion according to RECIST 1.1 determined by multiphasic CT or MRI (performed within 28 days before randomization)\n* ECOG performance status of 0 to 2\n\nExclusion Criteria:\n\n* Documented evidence of disease progression while on treatment (including SSAs) for locally advanced unresectable or metastatic disease\n* Known central nervous system metastases\n* Consecutive treatment with long-acting SSAs for more than 6 months before randomization\n* Carcinoid symptoms that are refractory to treatment (according to the Investigator's judgement) with conventional doses of octreotide LAR or lanreotide ATG and/or to treatment with daily doses of ≤600 µg of octreotide IR\n* Previous treatment with more than 1 cycle of targeted therapies such as mTOR inhibitors or vascular endothelial growth factor inhibitors, or more than 1 cycle of chemotherapy or interferon for GEP-NET\n* Treatment of GEP-NET with trans-arterial chemoembolization or trans-arterial embolization within 12 months before screening\n* Previously received radioligand therapy (PRRT) at any time","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"CAM2029","description":"CAM2029 (octreotide subcutaneous depot) 20 mg will be administered every 2 weeks as a subcutaneous injection"},{"type":"DRUG","name":"Octreotide LAR","description":"Octreotide LAR 30 mg will be administered every 4 weeks as an intramuscular injection"},{"type":"DRUG","name":"Lanreotide ATG","description":"Lanreotide ATG 120 mg will be administered every 4 weeks as a deep subcutaneous injection"}],"primaryOutcomes":[{"measure":"Progression-free survival (PFS) as assessed by a Blinded Independent Review Committee (BIRC)","description":"PFS is defined as time from the date of randomization to the date of the first documented disease progression as per RECIST 1.1 or death due to any cause (whichever occurs first)","timeFrame":"From date of randomization until disease progression or death due to any cause, whichever comes first, assessed up to 48 months"}],"secondaryOutcomes":[{"measure":"Overall survival","description":"The time from the date of randomization to the date of death due to any cause","timeFrame":"Up to 2 years following the primary efficacy analysis"},{"measure":"PFS as assessed by local Investigators","description":"PFS is defined as time from the date of randomization to the date of the first documented disease progression as per RECIST 1.1 or death due to any cause (whichever occurs first)","timeFrame":"From date of randomization until disease progression or death due to any cause, whichever comes first, assessed up to 48 months"},{"measure":"Overall response rate","description":"The proportion of patients with best overall response of complete response (CR) or partial response (PR), as per BIRC according to RECIST 1.1","timeFrame":"From date of randomization until disease progression, assessed up to 48 months"},{"measure":"Disease control rate","description":"The proportion of patients with a best overall response of CR, PR or stable disease (SD), as per BIRC according to RECIST 1.1","timeFrame":"From date of randomization until disease progression, assessed up to 48 months"},{"measure":"Time to tumor response","description":"The time from the date of randomization to the first documented response of CR or PR, as per BIRC according to RECIST 1.1","timeFrame":"From date of randomization until disease progression, assessed up to 48 months"},{"measure":"Duration of response","description":"The time from the date of the first documented response of CR or PR to the date of the first documented progression or death due to underlying cancer, as per BIRC according to RECIST 1.1","timeFrame":"From date of randomization until disease progression or death due to underlying cancer, whichever comes first, assessed up to 48 months"},{"measure":"Incidence of treatment-emergent adverse events","description":null,"timeFrame":"From screening to the safety follow-up, assessed up to 6 years"}],"publications":[{"pmid":"38229199","citation":"Singh S, Ferone D, Capdevila J, Chan JA, de Herder WW, Halperin D, Mailman J, Hellstrom L, Liedman H, Svedberg A, Tiberg F. Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET. Trials. 2024 Jan 16;25(1):58. doi: 10.1186/s13063-023-07834-8."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05050942"},{"nctId":"NCT06169124","title":"Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors","officialTitle":"A Phase II Study of Androgen Receptor (AR) Inhibition by Darolutamide in Combination With Leuprolide Acetate and Exemestane in Recurrent Adult-Type Ovarian Granulosa Cell Tumor","summary":"This phase II trial tests how well darolutamide in combination with leuprolide acetate and exemestane works in treating patients with ovarian granulosa cell tumors that have come back after a period of improvement (recurrent). Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Leuprolide acetate is in a class of medications called gonadotropin-releasing hormone agonists. It works by decreasing the amount of certain hormones in the body. Exemestane is in a class of medications called aromatase inhibitors which has anti-estrogen and anticancer activities. Exemestane binds to and inhibits the enzyme aromatase, thereby blocking the conversion of androgens to estrogens. This lowers estrogen levels in the blood circulation causing the tumor cells to grow more slowly or stop growing completely. The combination of darolutamide, leuprolide acetate, and exemestane may be an effective approach to shrinking or stabilizing recurrent ovarian granulosa cell tumors or preventing them from coming back.","detailedDescription":"PRIMARY OBJECTIVE:\n\nI. To determine the objective response rate of darolutamide, leuprolide acetate, and exemestane in recurrent adult-type granulosa cell tumors of the ovary (AGCT).\n\nSECONDARY OBJECTIVES:\n\nI. To determine duration of response of darolutamide, leuprolide acetate, and exemestane in recurrent adult-type granulosa cell tumors of the ovary (AGCT).\n\nII. To determine progression-free survival of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT).\n\nIII. To determine overall survival of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT).\n\nIV. To elucidate the toxicities of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT).\n\nEXPLORATORY OBJECTIVE:\n\nI. To determine biomarkers predictive of response to darolutamide, leuprolide acetate, and exemestane.\n\nOUTLINE:\n\nPatients receive exemestane orally (PO) once daily (QD) and darolutamide PO twice daily (BID) starting on days -14 to -7 prior to cycle 1, day 1 (C1D1) and then on days 1-28 of each cycle. Patients receive leuprolide acetate intramuscularly (IM) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo chest computed tomography (CT) or chest x-ray and CT, magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT as well as blood sample collection throughout the study. Patients undergo collection of archived tissue during screening.\n\nUpon completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.","peptideSlugs":["leuprolide"],"peptideNames":["Leuprolide"],"conditions":["Adult Ovarian Granulosa Cell Tumor"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"},"collaborators":[{"name":"NRG Oncology","slug":"nrg-oncology","class":"OTHER"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":17,"dates":{"start":"2024-02-08","primaryCompletion":"2026-02-10","completion":"2027-07-24","firstPosted":"2023-12-13","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":66,"countries":["United States"],"locations":[{"facility":"Cedars-Sinai Medical Center","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Helen F Graham Cancer Center","status":null,"city":"Newark","state":"Delaware","country":"United States","latitude":39.68372,"longitude":-75.74966},{"facility":"Medical Oncology Hematology Consultants PA","status":null,"city":"Newark","state":"Delaware","country":"United States","latitude":39.68372,"longitude":-75.74966},{"facility":"Saint Alphonsus Cancer Care Center-Boise","status":null,"city":"Boise","state":"Idaho","country":"United States","latitude":43.6135,"longitude":-116.20345},{"facility":"Saint Alphonsus Cancer Care Center-Caldwell","status":null,"city":"Caldwell","state":"Idaho","country":"United States","latitude":43.66294,"longitude":-116.68736},{"facility":"Kootenai Health - Coeur d'Alene","status":null,"city":"Coeur d'Alene","state":"Idaho","country":"United States","latitude":47.67768,"longitude":-116.78047},{"facility":"Saint Alphonsus Cancer Care Center-Nampa","status":null,"city":"Nampa","state":"Idaho","country":"United States","latitude":43.54072,"longitude":-116.56346},{"facility":"Kootenai Clinic Cancer Services - Post Falls","status":null,"city":"Post Falls","state":"Idaho","country":"United States","latitude":47.71796,"longitude":-116.95159},{"facility":"Kootenai Clinic Cancer Services - Sandpoint","status":null,"city":"Sandpoint","state":"Idaho","country":"United States","latitude":48.27659,"longitude":-116.55325},{"facility":"Northwestern University","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Carle at The Riverfront","status":null,"city":"Danville","state":"Illinois","country":"United States","latitude":40.12448,"longitude":-87.63002},{"facility":"Northwestern Medicine Cancer Center Kishwaukee","status":null,"city":"DeKalb","state":"Illinois","country":"United States","latitude":41.92947,"longitude":-88.75036},{"facility":"Carle Physician Group-Effingham","status":null,"city":"Effingham","state":"Illinois","country":"United States","latitude":39.12004,"longitude":-88.54338},{"facility":"Northwestern Medicine Cancer Center Delnor","status":null,"city":"Geneva","state":"Illinois","country":"United States","latitude":41.88753,"longitude":-88.30535},{"facility":"Northwestern Medicine Grayslake Outpatient Center","status":null,"city":"Grayslake","state":"Illinois","country":"United States","latitude":42.34447,"longitude":-88.04175},{"facility":"Northwestern Medicine Lake Forest Hospital","status":null,"city":"Lake Forest","state":"Illinois","country":"United States","latitude":42.25863,"longitude":-87.84063},{"facility":"Carle Physician Group-Mattoon/Charleston","status":null,"city":"Mattoon","state":"Illinois","country":"United States","latitude":39.48309,"longitude":-88.37283},{"facility":"Northwestern Medicine Orland Park","status":null,"city":"Orland Park","state":"Illinois","country":"United States","latitude":41.63031,"longitude":-87.85394},{"facility":"Carle Cancer Center","status":null,"city":"Urbana","state":"Illinois","country":"United States","latitude":40.11059,"longitude":-88.20727},{"facility":"Northwestern Medicine Cancer Center Warrenville","status":null,"city":"Warrenville","state":"Illinois","country":"United States","latitude":41.81781,"longitude":-88.1734},{"facility":"Ascension Saint Vincent Indianapolis Hospital","status":null,"city":"Indianapolis","state":"Indiana","country":"United States","latitude":39.76838,"longitude":-86.15804},{"facility":"University of Iowa/Holden Comprehensive Cancer Center","status":null,"city":"Iowa City","state":"Iowa","country":"United States","latitude":41.66113,"longitude":-91.53017},{"facility":"MaineHealth Maine Medical Center- Scarborough","status":null,"city":"Scarborough","state":"Maine","country":"United States","latitude":43.57814,"longitude":-70.32172},{"facility":"Trinity Health Saint Joseph Mercy Hospital Ann Arbor","status":null,"city":"Ann Arbor","state":"Michigan","country":"United States","latitude":42.27756,"longitude":-83.74088}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Physicians should consider the following when evaluating if the patient is appropriate for this protocol:\n\n  * Patients must have adequate health that permits completion of the study requirements and required follow up\n  * For patients with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infection:\n\n    * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n    * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n    * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n  * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n\nIn addition:\n\n* The effects of the combination of darolutamide, leuprolide acetate, and exemestane on the developing human fetus are unknown. For this reason, and because androgen receptor inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 1 month following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately\n\n  * Submission of tissue is required. Investigators should check with their pathology department regarding release of tissue before approaching patients about participation in the trial\n  * Histologically confirmed diagnosis of recurrent adult-type granulosa cell tumor\n  * Patient must have measurable disease. Measurable disease is defined in the protocol per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI\n  * Patient must have had ≥1 treatment regimen\n  * Subject must have progressed on an aromatase inhibitor (letrozole, exemestane, anastrozole) in a prior treatment line\n  * Age ≥ 18 years\n  * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2\n  * Not pregnant and not nursing\n  * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\\^3\n  * Platelets ≥ 100,000 cells/mm\\^3\n  * Hemoglobin ≥ 8 g/dl\n  * Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula\n  * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)\n  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN\n  * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better\n  * No active infection requiring parenteral antibiotics\n  * Patients with current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube\n  * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information\n\nExclusion Criteria:\n\n* Prior treatment with AR inhibitors\n* Known hypersensitivity to the study drugs or their ingredients","minimumAge":"18 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"PROCEDURE","name":"Biospecimen Collection","description":"Undergo archived tissue and blood sample collection"},{"type":"PROCEDURE","name":"Chest Radiography","description":"Undergo chest x-ray"},{"type":"PROCEDURE","name":"Computed Tomography","description":"Undergo CT and/or PET/CT"},{"type":"DRUG","name":"Darolutamide","description":"Given PO"},{"type":"DRUG","name":"Exemestane","description":"Given PO"},{"type":"DRUG","name":"Leuprolide Acetate","description":"Given IM"},{"type":"PROCEDURE","name":"Magnetic Resonance Imaging","description":"Undergo MRI"},{"type":"PROCEDURE","name":"Positron Emission Tomography","description":"Undergo PET/CT"}],"primaryOutcomes":[{"measure":"Objective response rate","description":"Defined as a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Exact 95% confidence limits, accounting for interim analysis, will be provided in the final report.","timeFrame":"Within 9 months of initiating study treatment"}],"secondaryOutcomes":[{"measure":"Duration of response","description":"Median duration of response with a corresponding 95% confidence interval will be estimated. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since date of study entry, including the baseline measurements.","timeFrame":"From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years"},{"measure":"Progression-free survival (PFS)","description":"Will be graphed using Kaplan-Meier methods. Median PFS will be estimated with corresponding 95% confidence intervals.","timeFrame":"From study entry to time of progression or death, whichever occurs first, or date of last contact with known progression free status if neither progression nor death has occurred, assessed up to 5 years"},{"measure":"Overall survival (OS)","description":"Will be graphed using Kaplan-Meier methods. Median OS will be estimated with corresponding 95% confidence intervals.","timeFrame":"From study entry to time of death or the date of last contact, assessed up to 5 years"},{"measure":"Incidence of adverse events","description":"Common Terminology Criteria for Adverse Events version 5 will be used to grade and categorize adverse events. Safety will be assessed beginning with the initial dose of any treatment. Descriptive statistics, including frequencies of maximum grade of adverse events by term and category will be reported. Adverse events categorized as grade 5 will be individually reported.","timeFrame":"Up to 5 years"}],"publications":[{"pmid":"42070324","citation":"Erfani H, Martynova A, Matsuzaki S, Matsuo K, Roman LD, Sood AK, Kurnit KC, Westin SN. Androgen receptor as a therapeutic target in endometrial cancer: a narrative review. Int J Gynecol Cancer. 2026 Jun;36(6):104698. doi: 10.1016/j.ijgc.2026.104698. Epub 2026 Apr 11."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06169124"},{"nctId":"NCT06548490","title":"GLP-1R Agonist Treatment for Opioid Use Disorder","officialTitle":"GLP-1R Agonist Treatment for Opioid Use Disorder","summary":"The goal of this clinical trial is to learn if semaglutide can reduce illicit opioid use in adults in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment. The main question it aims to answer is:\n\n• Does semaglutide increase the likelihood that participants will refrain from using illicit and nonprescribed opioids?\n\nThe investigators will compare semaglutide to a placebo (a needle prick that contains no drug) to see if semaglutide works to reduce use of illicit and nonprescribed opioids.\n\nThe participants will:\n\n* Take semaglutide or a placebo every week for 12 weeks\n* Visit the clinic every week for urine drug screening and pregnancy testing, vital signs, and to complete mental health and drug use questionnaires\n* Complete smartphone surveys sent at set times during the study","detailedDescription":"The purpose of this study is to determine whether 12 weeks of once-weekly treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, semaglutide, will reduce illicit opioid use over a 19 week period (129-172 days) among individuals in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment (i.e., medication for opioid use disorder; MOUD). Following successful consent and initiation of screening, participants will complete a baseline evaluation and begin a baseline data collection period. If screened into the study, they will be randomly assigned to semaglutide or placebo control arms, in a 1:1 ratio using a permuted-block randomization algorithm stratified by site and MOUD, and begin a 1-week baseline period. Semaglutide (injector pen) or placebo will be administered as a subcutaneously (SC) once per week for 12 weeks, starting at a dose of 0.25 mg SC and advanced on a fixed-flexible dose schedule, based on tolerability, to a dose of 1.0 mg SC per week, or the maximum tolerated dose if less than 1.0 mg. Participants will receive study intervention in an outpatient setting for a total of 12 weeks. After the 12-week intervention, participants will discontinue semaglutide or placebo and be observed for an additional week (wash-out period). A final follow-up visit will then take place approximately 4 weeks after the washout visit (calculated as 18 weeks after Baseline/Treatment Visit 1).\n\nDuring each study visit, participants will undergo urine drug screening and pregnancy testing, vital signs collection, and complete mental health and drug use questionnaires. Participants will also complete smartphone surveys sent at set times during the study. Blood samples will be collected at 2 of the visits (screening and the study week 14) and a physical examination and medical history collection will be done at the baseline visit.","peptideSlugs":["semaglutide","glucagon"],"peptideNames":["Semaglutide","Glucagon"],"conditions":["Opioid Use Disorder","Opioid Abuse and Addiction","Narcotic-Related Disorders","Substance-Related Disorders","Chemically-Induced Disorders","Mental Disorder","Opioid"],"keywords":["Opiate treatment","Opioid treatment","Glucagon-Like Peptide-1 Agonist","Opioid use disorder","Semaglutide"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Milton S. Hershey Medical Center","slug":"milton-s-hershey-medical-center","class":"OTHER"},"collaborators":[{"name":"New York University","slug":"new-york-university","class":"OTHER"},{"name":"University of Maryland","slug":"university-of-maryland","class":"OTHER"},{"name":"National Institute on Drug Abuse (NIDA)","slug":"national-institute-on-drug-abuse-nida","class":"NIH"},{"name":"Stanley Street Treatment and Resources (SSTAR)","slug":"stanley-street-treatment-and-resources-sstar","class":"UNKNOWN"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":200,"dates":{"start":"2025-01-13","primaryCompletion":"2027-04","completion":"2027-04","firstPosted":"2024-08-12","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":4,"countries":["United States"],"locations":[{"facility":"University of Maryland Baltimore","status":"COMPLETED","city":"Baltimore","state":"Maryland","country":"United States","latitude":39.29038,"longitude":-76.61219},{"facility":"Stanley Street Treatment and Resources","status":"NOT_YET_RECRUITING","city":"Fall River","state":"Massachusetts","country":"United States","latitude":41.70149,"longitude":-71.15505},{"facility":"NYU Langone Health","status":"RECRUITING","city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Pennsylvania Psychiatric Institute","status":"RECRUITING","city":"Harrisburg","state":"Pennsylvania","country":"United States","latitude":40.2737,"longitude":-76.88442}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 18 to 75 years.\n* Body mass index (BMI) \\> 18.\n* Able and willing to provide informed consent prior to any study-related activities.\n* Current diagnosis of Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-5 Opioid Use Disorder (OUD) as per the Mini International Neuropsychiatric Interview (MINI) or per the site clinic diagnosis. Patients are eligible if they have a MINI \\> 3 (\"moderate\" or \"severe\" in the \"Specify If\" box in the Substance Use Disorder (Non-Alcohol) module for the category of opiates).\n* Currently receiving outpatient treatment for OUD and at least 2 weeks on buprenorphine (BUP) or 4 weeks on methadone at the study site and/or at an associated clinic at the time of enrollment.\n* Have at least 1 urine test positive for opioids after 2 weeks on BUP or 4 weeks on methadone.\n* Have positive self-reporting of opioid use after 2 weeks on BUP or 4 weeks on methadone.\n* If capable of becoming pregnant and of childbearing age, is not pregnant (confirmed) or breastfeeding at the time of enrollment and agrees to use a medically accepted method of birth control or or to abstain from sexual activity that could result in pregnancy (if applicable) while in the study.\n* Able to read and communicate in English to the level required to accept standard care and complete all study requirements.\n* Able and willing to engage/adhere to the entirety of the study protocol (19 weeks).\n* Not currently a prisoner.\n\nExclusion Criteria:\n\n* Age \\< 18 or \\> 75 years.\n* BMI \\<18.\n* Individuals who are pregnant, planning pregnancy, breastfeeding, or unwilling to use adequate contraceptive measures.\n* Current use of glucagon-like peptide 1 receptor (GLP-1R) agonist.\n* History of angioedema, serious hypersensitivity reaction, or anaphylactic reaction to semaglutide or another GLP-1R agonist.\n* Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome Type 2 (MEN 2) or thyroid nodule.\n* Type 1 diabetes or history of diabetic ketoacidosis.\n* Type 2 diabetes mellitus or current use of a dipeptidyl peptidase-4 (DPP-4) inhibitor.\n* Past 30-day use of Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide.\n* Hypoglycemia on intake visit (blood glucose \\< 60 mg/dL).\n* End-stage renal failure, on dialysis, or glomerular filtration rate (GFR) \\<30 mL/min per 1.73 square meters or previous renal transplant.\n* End stage liver disease or previous liver transplant.\n* Current or past diagnosis of pancreatitis, gastroparesis, or other severe gastrointestinal (GI) disease.\n* Current or past diagnosis of gallbladder disease or gallstones.\n* Serious cardiovascular disease within the past 6 months (e.g. uncontrolled hypertension, heart failure, significant cardiac arrhythmias, myocardial infarction, presence of angina pectoris, symptomatic coronary artery disease, deep vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve or aortic stenosis, hypertrophic cardiomyopathy, stroke).\n* Severe co-occurring psychiatric disorder (e.g., bipolar disorder, psychotic disorder, schizophrenia), and/or history or evidence of organic brain disease or dementia that would compromise safety or compliance with the study protocol in the opinion of the site principal investigator (PI) and/or physician. As there is no specific scale that determines this, this will include the Site PI/physician determining if the potential participant shows consistency in decision making and if they are alert and oriented to time, date, day and location.\n* Significant risk of suicide requiring a different/higher level of care, according to the clinical judgment of the study physician or site principal investigator, or history of suicide attempts within the past 1 year, unless participation is cleared by clinician assessment and/or judgment. A Columbia-Suicide Severity Rating Scale (C-SSRS) indicating a history of suicide attempts within the past year, or active suicidal ideation within the past 1 month, will qualify as significant risk of suicide.\n* Treatment with any investigational drug in the one month preceding the study.\n* Any contraindication to both methadone and BUP.\n* Any contraindication to a GLP-1R agonist.\n* Previous randomization for participation in this trial.\n* Any other condition at screening that precludes safe participation in the trial in the judgment of the site PI or study physician.\n* Plans for travel outside of the local area over the 19 weeks (1 week of baseline, 12 weeks of medication, 1 week wash-out, and follow-up after a further 28 days) that would interfere with visits during the study period or other logistic factors that would make it difficult to commit to the entire duration of study.\n* Currently a prisoner.","minimumAge":"18 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide Pen Injector","description":"Semaglutide will be provided using an injection pen"},{"type":"DRUG","name":"Placebo","description":"Placebo will be a dry needle stick; no substances will be injected"}],"primaryOutcomes":[{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 2"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 3"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 4"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 5"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 6"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 7"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 8"},{"measure":"Number of participants being abstinent from illicit and nonprescribed opioids.","description":"Each week in the 12 week trial period will be rated as abstinent if both urine test and participants' report by Timeline FollowBack (TLFB) questionnaire are negative for illicit/non-prescribed opioids, or urine is negative and TLFB missing, or TLFB negative and urine missing; and not abstinent otherwise (either urine positive, or TLFB positive, or both are missing). For certain opioids (e.g., fentanyl), declining rates in urine will be considered negative for usage.","timeFrame":"Study week 9"}],"secondaryOutcomes":[{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 1"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 2"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 5"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 9"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 13"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 14"},{"measure":"Self-reported opioid craving scores as assessed via smartphone surveys","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 18"},{"measure":"Self-reported opioid craving as assessed via In-person Cravings Scales scores","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 2"},{"measure":"Self-reported opioid craving as assessed via In-person Cravings Scales scores","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 3"},{"measure":"Self-reported opioid craving as assessed via In-person Cravings Scales scores","description":"Validated 0-4 scale measuring desire/intention to use drug where 0 is no desire/intention and 4 is the highest desire/intention","timeFrame":"Study week 4"}],"publications":[{"pmid":"41168808","citation":"Freet CS, Shuler K, Kawasaki S, Weintraub E, Greenblatt A, Kladney M, Nunes E, Foster KL, Kong L, Raja-Khan N, Cleveland HH, Grigson PS, Bunce SC, Brick TR, Nyland JE. Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with OUD: a randomized, double-blind, placebo-controlled clinical trial protocol. Addict Sci Clin Pract. 2025 Oct 30;20(1):89. doi: 10.1186/s13722-025-00618-2."},{"pmid":"40502777","citation":"Freet CS, Shuler K, Kawasaki S, Weintraub E, Greenblatt A, Kladney M, Nunes E, Foster KL, Kong L, Raja-Khan N, Cleveland HH, Grigson PS, Bunce SC, Brick TR, Nyland JE. Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with treatment-refractory OUD: A randomized, double-blind, placebo-controlled clinical trial protocol. Res Sq [Preprint]. 2025 May 26:rs.3.rs-6666196. doi: 10.21203/rs.3.rs-6666196/v1."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06548490"},{"nctId":"NCT07191873","title":"Tirzepatide in Idiopathic Intracranial Hypertension Trial","officialTitle":"A Phase IV Placebo-controlled Single Center Trial for Tirzepatide in Idiopathic Intracranial Hypertension Trial (TIIHT)","summary":"This will be a randomized, double-blind, parallel, placebo-controlled trial of 60 participants. The primary analysis will be a statistical comparison of the estimates of the mean difference in the 12-month change in intracranial pressure (ICP) between participants assigned to the tirzepatide and Placebo arms in 1:1 randomization using the intention-to-treat (ITT) population. Hypothesis testing will be performed using analysis of covariance (ANCOVA), with the treatment indicator as the independent variable and the 12-month change in ICP as the dependent variable. Models will include baseline ICP as a covariate. This primary endpoint will use a significance level of 0.05 to declare significance.","detailedDescription":null,"peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Idiopathic Intracranial Hypertension (IIH)"],"keywords":["IIH","BMI","Eye Pressure","Headache"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Duke University","slug":"duke-university","class":"OTHER"},"collaborators":[{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":60,"dates":{"start":"2026-08","primaryCompletion":"2027-08","completion":"2028-08","firstPosted":"2025-09-25","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Duke University Medical Center","status":null,"city":"Durham","state":"North Carolina","country":"United States","latitude":35.99403,"longitude":-78.89862}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Signs and symptoms of increased intracranial pressure:\n\n   1. headaches, tinnitus, visual obscurations, papilledema;\n   2. absence of localizing findings on neurological examination (except for VI nerve palsy);\n   3. no secondary causes identified on imaging, e.g., hydrocephalus, space- occupying lesion;\n   4. elevated lumbar puncture (LP) opening pressure (OP) ≥25 cm H2O in lateral decubitus position with legs extended (\\>= (≥ 20cm H2O if one of the following is present: pulse synchronous tinnitus, abducens palsy, Frisen grade II papilledema, transverse venous sinus stenosis, partially empty sella or enlarged optic nerve sheath on magnetic resonance imaging (MRI);\n   5. the patient is awake and alert.\n2. BMI ≥30 kg/m2\n3. Age 18-60 years of age\n4. Unilateral or bilateral papilledema\n5. Able to provide informed consent\n6. Women of child-bearing age must use birth control (non-oral contraceptive method or add a barrier method of contraception).\n\nExclusion Criteria:\n\n1. Previous bariatric surgery\n2. Prior intervention for high ICP including optic nerve sheath fenestration (ONSF), venous stenting and/or shunting\n3. Taking another GLP-1 agonist, another drug that can interfere with the GLP-1 agonist, or any other anti-obesity medication\n4. History of pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), history of gallbladder disease, ulcerative colitis, Crohn's disease, or history of hypersensitivity reaction in response to the drug\n5. Pregnancy or planning a pregnancy in the next 12 months or currently breastfeeding\n6. Other disorders causing visual loss and/or anomalous optic nerve\n7. Taking another medication to lower ICP in IIH (if previously taking another medication for ICP must be off this medication for at least 30 days prior to enrollment)\n8. No change in headache medications in the past 60 days\n9. Venous sinus thrombosis on magnetic resonance venography (MRV)\n10. Papilledema Frisen Grade III, IV or fulminant IIH\n11. Mean perimetric deviation ≤ -7 dB\n12. CSF contents outside of normal limits\n13. Uncontrolled hypertension (≥140mmHg/90 mmHg)\n14. Anemia (hemoglobin \\[Hgb\\] ≤ 8.0g/dL)\n15. Diagnosed sleep apnea with continuous positive airway pressure (CPAP) use\n16. Exposure to a drug, substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis such as lithium, vitamin A, various cyclines\n17. eGFR \\< 30 ml/min/1.73m2\n18. Type II diabetes","minimumAge":"18 Years","maximumAge":"60 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months"},{"type":"DRUG","name":"Tirzepatide Placebo","description":"Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months"}],"primaryOutcomes":[{"measure":"Change in intracranial pressure in Idiopathic Intracranial Hypertension (IIH) patients","description":"Assessed by opening pressure via lumbar puncture (LP) in the left lateral decubitus position and measured in cm H2O.","timeFrame":"From enrollment to end of treatment at 12 months"}],"secondaryOutcomes":[{"measure":"Retinal Nerve Fiber Layer (RNFL) Thickness on optical coherence tomograhy (OCT)","description":"Mean change in RNFL thickness","timeFrame":"From enrollment to end of treatment at 12 months"},{"measure":"Change in Frisen papilledema grade on fundus photography","description":"The Frisen scale ranges from 0 (normal optic disc) to 5 (severe degree of edema).","timeFrame":"From enrollment to the end of treatment at 12 months"},{"measure":"Change in perimetric mean deviation","description":"Perimetric Mean Deviation (MD) is a key visual field index that represents the average point-by-point difference between a patient's visual field and the normal, age-matched expected visual field.","timeFrame":"From enrollment to end of treatment at 12 months"}],"publications":[{"pmid":"25449938","citation":"Spitze A, Lam P, Al-Zubidi N, Yalamanchili S, Lee AG. Controversies: Optic nerve sheath fenestration versus shunt placement for the treatment of idiopathic intracranial hypertension. Indian J Ophthalmol. 2014 Oct;62(10):1015-21. doi: 10.4103/0301-4738.146012."},{"pmid":"24296367","citation":"Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin. 2014 Winter;54(1):1-11. doi: 10.1097/IIO.0b013e3182aabf11. No abstract available."},{"pmid":"26888960","citation":"Mollan SP, Ali F, Hassan-Smith G, Botfield H, Friedman DI, Sinclair AJ. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):982-92. doi: 10.1136/jnnp-2015-311302. Epub 2016 Feb 17."},{"pmid":"33472926","citation":"Miah L, Strafford H, Fonferko-Shadrach B, Hollinghurst J, Sawhney IMS, Hadjikoutis S, Rees MI, Powell R, Lacey A, Pickrell WO. Incidence, Prevalence, and Health Care Outcomes in Idiopathic Intracranial Hypertension: A Population Study. Neurology. 2021 Feb 22;96(8):e1251-e1261. doi: 10.1212/WNL.0000000000011463."},{"pmid":"30356129","citation":"Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar;33(3):478-485. doi: 10.1038/s41433-018-0238-5. Epub 2018 Oct 24."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07191873"},{"nctId":"NCT07430228","title":"Efficacy of Intravenous Oxytocin to Speed Recovery After THA","officialTitle":"Efficacy of Intravenous Oxytocin to Speed Recovery After Total Hip Arthroplasty","summary":"The purpose of this study is to test whether perioperative intravenous (IV) oxytocin compared to placebo results in faster recovery in disability as measured by daily steps over 56 days after Total Hip Arthroplasty (THA).","detailedDescription":"This is a single center, NIH funded clinical study at Atrium Health Wake Forest Baptist Medical Center. The investigators will utilize a triple-masked, parallel group, randomized design to compare intravenous (IV) oxytocin to placebo to determine IV oxytocin's actions on speed of recovery from physical disability and postoperative pain after Total Hip Arthroplasty (THA).","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["Total Hip Arthroplasty"],"keywords":["Intravenous (IV) oxytocin","Postoperative pain","Disability"],"conditionGroups":[{"slug":"pain","label":"Pain"}],"sponsor":{"name":"Wake Forest University Health Sciences","slug":"wake-forest-university-health-sciences","class":"OTHER"},"collaborators":[{"name":"National Institute of Neurological Disorders and Stroke (NINDS)","slug":"national-institute-of-neurological-disorders-and-stroke-ninds","class":"NIH"}],"status":{"raw":"ENROLLING_BY_INVITATION","group":"active","label":"Enrolling by invitation"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":80,"dates":{"start":"2026-08","primaryCompletion":"2027-12","completion":"2027-12","firstPosted":"2026-02-24","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Atrium Health Wake Forest Baptist","status":null,"city":"Winston-Salem","state":"North Carolina","country":"United States","latitude":36.09986,"longitude":-80.24422}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Male or female \\> 18 and ≤75 years of age\n* Scheduled for unilateral, primary total hip arthroplasty surgery\n* Generally in good health as determined by the Principal Investigator based on prior medical history, and as assessed to be American Society of Anesthesiologists physical status 1, 2, or 3\n* Willing to perform the study procedures\n* Able to read and write English and have a stable residence.\n\nExclusion Criteria:\n\n* Hypersensitivity to any ingredient in Pitocin® (marketed preparation of oxytocin for parenteral injection)\n* Latex allergy\n* Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the participant at increased risk (e.g., active gynecologic disease in which increased tone would be detrimental such as uterine fibroids with ongoing bleeding)\n* Women who are pregnant, are currently nursing or lactating, or have been pregnant within 2 years\n* Current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval.\n* Past or current history of hyponatremia or at risk for hyponatremia; anyone taking thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, desmopressin, Selective Serotonin Reuptake Inhibitors (SSRI's), Monoamine oxidase inhibitors (MAOIs), or the recreational drug ecstasy.\n* Inability to complete questionnaires\n* Litigation or workers compensation related to their joint surgery\n* Taking \\> 100 mg morphine equivalents/day\n* Suffering from a psychotic disorder or a recent psychiatric hospitalization","minimumAge":"18 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"intravenous administration of oxytocin","description":"Single administration of oxytocin 26 micrograms administered intravenously over a period of 45 minutes."},{"type":"DRUG","name":"Placebo","description":"Saline will be administered intravenously over a period of 45 minutes"}],"primaryOutcomes":[{"measure":"Modeled daily steps trajectory","description":"Individual trajectories, adjusted for prognostic covariates, of daily steps will be constructed using an intercept on the first postoperative day and a slope a log of time dimension through day 56 using growth curve modeling. The intercept is in units of steps on the first post-discharge day with the lower number of steps indicating more disability and the slope is in units of logarithm of steps per day with the lower number indicating slower recovery from disability - Key models often classify adults into sedentary (\\<5,000 steps), low active (5,000-7,499), somewhat active (7,500-9,999), or active (≥10,000) trajectories.","timeFrame":"56 days after surgery"}],"secondaryOutcomes":[{"measure":"Modeled pain intensity trajectory","description":"Description: Individual trajectories, adjusted for prognostic covariates, of worst daily pain intensity scores (0-10 scale) from daily diaries will be constructed using an intercept on the first postoperative day and a slope a log of time dimension through day 56 using growth curve modeling. The intercept is pain score on the first post-discharge day with the higher score indicating more pain and the slope is in units of logarithm of pain score per day with the lower number indicating slower recovery from pain","timeFrame":"56 days after surgery"},{"measure":"Modeled disability assessments","description":"Individual trajectories, adjusted for prognostic covariates, of World Health Organization Disability Assessment Schedule (WHODAS) 2.0 scores from weekly diaries will be constructed using an intercept on the first postoperative day and a slope a log of time dimension through day 56 using growth curve modeling.\n\nEach item in the WHODAS 2.0 questionnaire is rated on a 5-point scale from 0 (none) to 4 (extreme or cannot do).\n\nTotal Range: 0-48 (Raw sum), where 0 is the minimum and 48 is maximum disability.\n\nA higher score signifies a greater level of disability.","timeFrame":"56 days after surgery"},{"measure":"Modeled opioid dosing trajectory","description":"Individual trajectories, adjusted for prognostic covariates, of daily opioid dose in milligrams of morphine equivalents from daily diaries will be constructed using an intercept on the first postoperative day and a slope a log of time dimension through day 56 using growth curve modeling. The intercept is in opioid dose on the first post-discharge day and the slope is in units of logarithm of opioid dose per day with the lower number indicating slower quicker reduction in opioid dose over time.","timeFrame":"56 days after surgery"},{"measure":"Modeled opioid cessation trajectory","description":": Individual trajectories, adjusted for prognostic covariates, of time to opioid cessation from daily diaries, in which each day is scored as taking opioids or not taking opioids. Opioid cessation for each individual is the last day they took an opioid. The trajectory for the likelihood of taking opioids will be determined using an intercept on the first postoperative day and a slope a log of time dimension through day 56 using growth curve modeling.","timeFrame":"56 days after surgery"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07430228"},{"nctId":"NCT07497880","title":"Efficacy and Safety of Oral KAI-7535 in Adult Participants Living With Obesity or Overweight With at Least 1 Weight-Related Comorbidity","officialTitle":"A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral KAI-7535 in Adult Participants Living With Obesity or Overweight With at Least 1 Weight-Related Comorbidity","summary":"The primary objective of this study is to determine the efficacy of oral KAI-7535 once daily compared with placebo on percent change in body weight in participants living with obesity or overweight, with at least 1 weight-related comorbidity, without diabetes mellitus. Efficacy in participants with type 2 diabetes mellitus will be evaluated. Safety and tolerability and other weight-related outcomes will be evaluated in both types of participants.","detailedDescription":null,"peptideSlugs":["glucagon"],"peptideNames":["Glucagon"],"conditions":["Obesity","Overweight"],"keywords":["Obesity","Overweight","Glucagon-like peptide-1","GLP-1","KAI-7535","Diabetes","Oral"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Kailera","slug":"kailera","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":320,"dates":{"start":"2026-04-06","primaryCompletion":"2027-07-07","completion":"2027-07-07","firstPosted":"2026-03-27","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":36,"countries":["Australia","United States"],"locations":[{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Chandler","state":"Arizona","country":"United States","latitude":33.30616,"longitude":-111.84125},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Irvine","state":"California","country":"United States","latitude":33.66946,"longitude":-117.82311},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Lincoln","state":"California","country":"United States","latitude":38.89156,"longitude":-121.29301},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Northridge","state":"California","country":"United States","latitude":34.22834,"longitude":-118.53675},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Hamden","state":"Connecticut","country":"United States","latitude":41.39593,"longitude":-72.89677},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Jupiter","state":"Florida","country":"United States","latitude":26.93422,"longitude":-80.09421},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Palm Springs","state":"Florida","country":"United States","latitude":26.6359,"longitude":-80.09615},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Pembroke Pines","state":"Florida","country":"United States","latitude":26.00315,"longitude":-80.22394},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Decatur","state":"Georgia","country":"United States","latitude":33.77483,"longitude":-84.29631},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Skokie","state":"Illinois","country":"United States","latitude":42.03336,"longitude":-87.73339},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"South Bend","state":"Indiana","country":"United States","latitude":41.68338,"longitude":-86.25001},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Kenner","state":"Louisiana","country":"United States","latitude":29.99409,"longitude":-90.24174},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Garden City","state":"Michigan","country":"United States","latitude":42.32559,"longitude":-83.33104},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Jefferson City","state":"Missouri","country":"United States","latitude":38.5767,"longitude":-92.17352},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Kansas City","state":"Missouri","country":"United States","latitude":39.09973,"longitude":-94.57857},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Spartanburg","state":"South Carolina","country":"United States","latitude":34.94957,"longitude":-81.93205},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Knoxville","state":"Tennessee","country":"United States","latitude":35.96064,"longitude":-83.92074},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Austin","state":"Texas","country":"United States","latitude":30.26715,"longitude":-97.74306},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Austin","state":"Texas","country":"United States","latitude":30.26715,"longitude":-97.74306},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Brownsville","state":"Texas","country":"United States","latitude":25.90175,"longitude":-97.49748},{"facility":"Kailera Clinical Site","status":"RECRUITING","city":"Farmers Branch","state":"Texas","country":"United States","latitude":32.92651,"longitude":-96.89612}],"eligibility":{"criteria":"Key Inclusion Criteria:\n\n* For participants without diabetes mellitus at screening and on Day 1, BMI ≥30 kilograms/square meter (kg/m\\^2) or BMI ≥27 kg/m\\^2 and a previous diagnosis of at least 1 of the following:\n\n  * Hypertension\n  * Dyslipidemia\n  * Obstructive sleep apnea\n  * Cardiovascular disease\n* For participants living with type 2 diabetes mellitus and BMI ≥27 kg/m\\^2 only:\n\n  * Diagnosis of type 2 diabetes mellitus\n  * On stable therapy for type 2 diabetes mellitus for at least 3 months prior to screening\n\nKey Exclusion Criteria:\n\n* For participants without diabetes:\n\n  * Laboratory evidence of diabetes\n  * Taking a concomitant medication for the indication of glycemic control\n* For participants living with type 2 diabetes mellitus only:\n\n  * History of diabetic ketoacidosis or hyperosmolar state/coma within 1 year of screening\n  * History of severe hypoglycemia or hypoglycemia unawareness within 1 year of screening\n  * History of proliferative diabetic retinopathy, diabetic maculopathy, or nonproliferative diabetic retinopathy that required acute treatment\n* Started medications that may cause significant weight change within 3 months prior to screening, including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers\n* Unstable weight defined as self-reported change in body weight exceeding 5% within 3 months prior to screening\n* Family or personal history of multiple endocrine neoplasia Type 2 or medullary thyroid carcinoma\n* Uncontrolled hypertension or unstable cardiovascular disease\n* History of chronic or acute pancreatitis\n* Known clinically significant gastric-emptying abnormality or chronic treatment with medications that directly affect gastrointestinal motility\n* History of suicide attempt\n* History of significant active or unstable major depressive disorder or other severe psychiatric disorder\n* Received treatment with semaglutide, tirzepatide, glucagon-like peptide-1 (GLP-1) receptor agonist, GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist, or glucagon receptor agonist within the last 3 months prior to screening\n\nNote: Additional inclusion/exclusion criteria may apply, per protocol.","minimumAge":"18 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"KAI-7535","description":"Oral tablets"},{"type":"DRUG","name":"Placebo","description":"Oral tablets"}],"primaryOutcomes":[{"measure":"Percent Change from Baseline in Body Weight at Week 44 for Participants Without Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"}],"secondaryOutcomes":[{"measure":"Change from Baseline in Body Weight at Week 44 for Participants Without Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"},{"measure":"Change from Baseline in Body Mass Index (BMI) at Week 44 for Participants Without Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"},{"measure":"Percentage of Participants at Week 44 with ≥5% and ≥10% Reduction in Body Weight for Participants Without Diabetes Mellitus","description":null,"timeFrame":"Week 44"},{"measure":"Percent Change from Baseline in Body Weight at Week 44 for Participants Living with Type 2 Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"},{"measure":"Change from Baseline in Body Weight at Week 44 for Participants Living with Type 2 Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"},{"measure":"Change from Baseline in BMI at Week 44 for Participants Living with Type 2 Diabetes Mellitus","description":null,"timeFrame":"Baseline, Week 44"},{"measure":"Percentage of Participants at Week 44 with ≥5% and ≥10% Reduction in Body Weight for Participants Living with Type 2 Diabetes Mellitus","description":null,"timeFrame":"Week 44"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07497880"},{"nctId":"NCT07559500","title":"Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD)","officialTitle":"Tirzepatide s Dopaminergic Effects in Alcohol Use Disorders (AUD), a Phase 1b Study","summary":"Background:\n\nGlucagon-like peptide 1 (GLP-1) agonist drugs are used to treat diabetes and aid weight loss. They may also help reduce cravings for drugs and alcohol. Researchers want to know if a GLP-1 drug (tirzepatide) can lessen the urge to drink in people with alcohol use disorder (AUD).\n\nObjective:\n\nTo learn how the brains of people with AUD respond to a GLP-1 drug.\n\nEligibility:\n\nPeople aged 21 to 65 years with AUD who are non-treatment seeking. They must be enrolled in protocol 14-AA-0181. Healthy volunteers are also needed.\n\nDesign:\n\nThis study consists of Part 1 and Part 2.\n\nPart 1 (Imaging Procedures): Five healthy volunteers will undergo 2 to 3 combined positron emission tomography/magnetic resonance imaging (PET/MRI) scans, with an interval of 2 to 3 weeks between scans. For each scan, a radioactive substance (tracer) will be administered intravenously. Participants will undergo PET/MRI scanning to assess brain activity during resting state. Methylphenidate (Ritalin) will be administered during each scan. Each imaging session will last approximately 2 hours. Tirzepatide and placebo will not be administered in Part 1. Participants with alcohol use disorder (AUD) are not included in Part 1. The purpose of this part of the study is to assess test/retest reproducibility of the PET/MRI combined scan measures.\n\nPart 2 (Randomization to Tirzepatide \\& Placebo): Participants will be randomized to receive either Tirzepatide or Placebo first. Healthy Volunteers and AUD participants will receive both treatments in a crossover design. Tirzepatide and placebo will be administered via subcutaneous injection (under the skin) once weekly for 2 to 3 weeks. This treatment period will be followed by 2 to 3 PET/MRI combined imaging scans described in the next paragraph. After a washout interval of approximately 2 to 3 weeks, participants will cross over to the alternate treatment (tirzepatide or placebo), administered once weekly for 2 to 3 weeks. This second treatment period will be followed by an additional 2 to 3 PET/MRI scans. Participants may receive up to 3 doses of tirzepatide and 3 doses of placebo.\n\nPart 2 (Imaging Procedures): Healthy Volunteers and participants with an AUD will undergo PET/MRI scans at two time points: following tirzepatide administration and following placebo administration. For each scan a radioactive substance (tracer) will be administered intravenously. Brain activity will be measured during PET/MRI acquisition during resting state. Methylphenidate will be administered during 1 of the scans at each time point. Each imaging session will last approximately 2 hours. Participants will wear a device to track their activity for at least 1 week before each set of scans. They will have tests of their thinking, memory, and attention.","detailedDescription":"Study Description:\n\nProtocol has 2 parts:\n\nPart 1 (n=5 healthy volunteers): Assess the reproducibility of striatal dopamine (DA) measures in response to iv methylphenidate (MP) using PET/MR combined scanning and the bolus infusion protocol in healthy controls.\n\nPart 2 (n=88, 44 healthy volunteers and 44 AUD): Evaluate Tirzepatide s brain dopaminergic effects in controls and participants with alcohol use disorder (AUD) as compared to placebo (2 injections 1 week apart from each other) on MP induced brain DA increases and functional reactivity using PET/fMRI, on dopamine D1 and D2 receptors and reactivity to alcohol and food cues. We hypothesize that Tirzepatide compared to placebo will (1) increase striatal dopamine D2 receptors while decreasing D1 receptors, (2) attenuate DA increases to MP and functional reactivity and (3) blunt the response to alcohol and food cues to a greater extent in AUD than control participants.\n\nPrimary Objectives:\n\nPart 1: Reproducibility of striatal DA measures\n\nPart 2: Effects of Tirzepatide on: striatal dopamine D1R and D2R availability; striatal DA increase; brain reactivity to MP and to food and alcohol cues in AUD and in healthy controls.\n\nSecondary Objectives:\n\nPart 1: Subjective responses to MP\n\nPart 2: Examine Tirzepatide s effects on subjective effects to MP, sleep, alcohol craving (AUD only), alcohol withdrawal symptoms (AUD only), food craving, locomotor activity, mood and weight.\n\nPrimary Endpoints:\n\nPart 1: Striatal DA changes with MP tested in two separate occasions\n\nPart 2: Striatal D1R and D2R availability; Striatal DA increases with MP; Brain functional reactivity to MP and to alcohol and food cues. Measures collected twice after placebo and after Tirzepatide\n\nSecondary Endpoints:\n\nSelf-reports of drug effects (Parts 1 \\& 2)\n\nSleep measures: actigraphy and self-reports (Part 2).\n\nAlcohol Craving (only AUD): Desire for Alcohol Questionnaire (DAQ). (Part 2)\n\nAlcohol Withdrawal (only AUD): Clinical Institute Withdrawal Assessment (CIWA) (Part 2)\n\nFood Craving: Food Cravings Questionnaire - State and Trait (FCQ S, FCQ-T) (Part 2)\n\nLocomotor activity: actigraphy (Part 2)\n\nMood: Profile of Mood States (POMS, Parts 1 \\& 2)\n\nExploratory Endpoints:\n\nPart 2:\n\n* Brain structure and function assessed by MRI (task and resting fMRI, structural MRI)\n* Cognitive Test Performance\n* Weight\n* Eating phenotypes","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Alcohol Use Disorder (AUD)"],"keywords":["Tirzepatide","Dopamine","Alcohol Use Disorder (AUD)","Normal Physiology","GLP-1"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute on Alcohol Abuse and Alcoholism (NIAAA)","slug":"national-institute-on-alcohol-abuse-and-alcoholism-niaaa","class":"NIH"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":176,"dates":{"start":"2026-05-20","primaryCompletion":"2031-12-31","completion":"2031-12-31","firstPosted":"2026-04-30","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institutes of Health Clinical Center","status":"RECRUITING","city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026}],"eligibility":{"criteria":"* INCLUSION CRITERIA:\n\nHealthy Volunteer Participants\n\nTo be eligible to participate in this study, an individual must meet the following criteria:\n\n1. Enrollment in 14AA0181.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. Male or female, ages 21-65 years old.\n4. Ability to understand and willingness to sign a written informed consent document.\n5. Have or had any prior experience with stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, or prescription stimulants (prescription or recreational use), whether or not they have had a past substance use disorder.\n\nAUD Participants\n\nTo be eligible, individuals with AUD must meet the following criteria:\n\n1. Enrollment in 14AA0181.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. Male or female, ages 21-65 years old.\n4. Ability to understand and willingness to sign a written informed consent document.\n5. DSM 5 diagnosis of mild to moderate AUD.\n6. Have or had any prior experience with stimulant drugs including cocaine, methylphenidate, amphetamine or methamphetamine, or prescription stimulants (prescription or recreational use), whether or not they have had a past substance use disorder.\n7. Minimum 2-year history of heavy drinking (SAMSHA s criteria for heavy drinking: for men 5 or more drinks/day on at least 5 different days per month; and for women 4 or more\n\n   drinks/day on at least 5 different days per month.\n8. Non treatment seeking AUD participants.\n\nEXCLUSION CRITERIA:\n\nAll Participants (Healthy Volunteers and AUD)\n\n1. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI\n2. Cannot lie comfortably flat on his/her back for up to 2 hours in the PET/MRI scanner.\n3. BMI \\<23 or \\>35 (but no more than 500 lbs). The PET/MRI scanner bed is tested to a weight limit of 500 lbs.\n4. Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam.\n5. Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 55 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study (i.e., within 24 hours before study procedures). Females must not be currently breastfeeding.\n6. Women using oral contraceptives (Part 2 of study). Women of childbearing age who are taking oral contraceptives will be required to switch to a non-oral hormonal contraceptive method (ie implants, injections, or IUDs) or add a barrier method (condoms) for the duration of the study and for 4 weeks after the last dose of study drug after explaining to them that Tirzepatide could make contraceptive less effective. We will not provide nonoral contraceptive medications to participants.\n7. Severe head trauma with loss of consciousness \\> 60 minutes\n8. Current severe mental illness (schizophrenia, bipolar disorder).\n9. Montgomery-Asberg depression rating scale (MADRS) total score \\> 35 or suicidal thoughts item score \\> 3, indicating severe depression or moderate suicidality, respectively.\n10. Thyroid cancer or family history of thyroid cancer or personal or family history of multiple endocrine neoplasia syndrome type-2 (MEN-2).\n11. History for cerebral aneurysm.\n12. Past or present history of chest pain and trouble breathing with activity.\n13. History of Heart Disease, Hypertension or Cardiovascular disorders.\n14. History of seizures, anxiety, panic attacks, psychosis or glaucoma which are contraindicated with receiving methylphenidate.\n15. History of gallbladder disease, pancreatitis, gastroparesis, diabetic retinopathy, acute kidney injury (AKI), as these are contraindicated for Tirzepatide.\n16. History of allergic reaction to methylphenidate, Tirzepatide or allergic reactions to dyes or preservatives.\n17. Major medical problems that can permanently impact brain function (e.g., seizures, psychosis, stroke, Alzheimer s disease, Parkinson s disease, traumatic brain injury with\n\n    loss of consciousness \\> 30 minutes, clinically significant arrhythmias except bradycardia, and HIV+).\n18. Clinically significant laboratory findings that could impact brain function or study procedures (e.g., active infections, significant EKG results, hepatic or renal failure) will be\n\n    exclusionary.\n19. Current DSM-5 diagnosis of a psychiatric disorder that required daily psychoactive medications (antidepressant, antipsychotics, stimulants, opioids, benzodiazepines or barbiturates) in the past two months and that could impact brain function at the time of the study as determined by history and clinical exam.\n20. History of moderate or severe SUD (other than nicotine in HV s, and nicotine, cannabis or alcohol for AUD participants).\n21. Daily current use (past 2 months) of the following drugs/medications are exclusionary: stimulant or stimulant-like drugs or medications (cocaine, methamphetamine, amphetamine, methylphenidate, modafinil); opioid drugs or medications; other GLP-1 or anti-diabetic drugs (e.g., insulin, sulfonylureas) medications, antianginal agents; antiarrhythmics; systemic corticosteroids; anticholinergics; anticoagulants; anticonvulsants; antidepressants with dopaminergic effects (bupropion, sertraline, and dopamine agonists like pramipexole and ropinirole); beta-blocker antihypertensives; antineoplastics; antipsychotics; anxiolytics (benzodiazepine or barbiturates); or lithium. Note that alcohol and cannabis use are not exclusionary but participants cannot be intoxicated on the day of study as evidence of alcohol in breathalyzer or cannabis in saliva. Caffeine and nicotine are permitted but participants will be asked to refrain from consuming caffeine or nicotine products (including cigarettes) two hours prior to the study. Antihistamines are also not exclusionary but should not be used on the day of study.\n22. \\*Non-English speakers (must also be able to read and comprehend English\n\n    * We are excluding non-English speakers since the study includes questionnaires that are validated for English and only some are available in Spanish. The fMRI paradigms also require that the subject be able to speak, read and comprehend English.\n\nNote that subjects will not be excluded from enrollment onto this study if their urine test or breath alcohol level (BAL) is positive for alcohol/drugs on initial screening. The following guidelines will be followed for positive drug/alcohol screens on study procedure days involving imaging scans and neuropsychological testing for all participants:\n\n* If a subject s breath alcohol (\\>0.08%) screen test is positive on days involving imaging (PET/MRI) and NP testing, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days resulting from positive breath alcohol screens. If subject continues to show up intoxicated they will be withdrawn.\n* If urine drug screen is positive for THC-COOH a saliva drug screen will be performed and subject may proceed with study day testing procedures if saliva results for THC are negative. If we are unable to perform the saliva drug screen for any reason, the study day procedures will be postponed. If the urine/saliva drug test is positive on the third rescheduled visit, the participant will be withdrawn from the study. Saliva THC is not required for determining eligibility.\n* If a participants urine drug screen test is positive for cocaine, heroin or methamphetamine after 3 days of rescheduling they will be excluded.","minimumAge":"21 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Drug approved for diabetes administered SQ. Subject is blind to drug."},{"type":"DRUG","name":"Placebo","description":"Placebo will be normal saline administered SQ. Subject is blind to drug."},{"type":"DRUG","name":"[11C]raclopride plus drug","description":"Radiotracer injection of \\[11C\\]raclopride during combined PET/MR scan to measure striatal dopamine release (Methylphenidate 0.25 mg/kg injected 45 minutes post radiotracer injection). Subject is not blind to this drug during scan."},{"type":"DRUG","name":"[11C]NNC-112","description":"\\[11C\\]NNC-112 PET/MR or PET/CT scan obtained without any drug intervention to measure dopamine D1 receptors."}],"primaryOutcomes":[{"measure":"Part 1 (n=5 healthy volunteers): We will assess the reproducibility of striatal dopamine (DA) measures in response to iv methylphenidate (MP) using PET/MR combined scanning and the bolus infusion protocol in healthy controls.","description":"We will measure dopamine in the brain. Dopamine is a chemical messenger that carries signals between brain cells. It plays a role in human behavior. It is also believed to play a role in addiction. In this study, we will use a combined scanner for PET and MRI to measure dopamine with the stimulant drug methylphenidate. Each scan will be done by getting a small amount of a radiotracer through an IV catheter. During each of the two PET/MRI scan sessions each subject will receive IV methylphenidate. We will look at the effects of methylphenidate on brain dopamine. We will also look at brain responses, mood and thinking. The results of each subject's scans will be compared to each other. We will also compare the results to other participants to see if we get similar information.","timeFrame":"We aim to have each subject (n=5) complete all study procedures within 60 days."},{"measure":"Part 2 (n=88, 44 healthy volunteers and 44 AUD) : Effects of Tirzepatide on striatal dopamine D1R and D2R availability; striatal DA increase; brain reactivity to MP and to food and alcohol cues in AUD and in healthy controls.","description":"We will measure dopamine levels in the brain. Dopamine is a chemical messenger that carries signals between brain cells. It plays a role in human behavior. It is also believed to play a role in addiction. In this study, we will use a combined scanner for PET and MRI to measure dopamine with the stimulant drug methylphenidate. We will look at the effects of methylphenidate on brain dopamine. To do this we will obtain imaging scans after the subject receives Tirzepatide and a Placebo. We will also look at brain responses, mood and thinking. Results from the same scans on two separate days will be compared to each other. We will also compare the results to other participants to see if we get similar information.","timeFrame":"We aim to have each subject complete study procedures within 90 days, but this could take longer. AUD participants will undergo a Follow Up phone call about 1 month after imaging scans are complete."}],"secondaryOutcomes":[{"measure":"Part 1: Subjective responses to MP","description":"The purpose of this research study is to measure dopamine in the brain. Dopamine is a chemical messenger that carries signals between brain cells. It plays a role in human behavior. It is also believed to play a role in addiction. In this study, we will use a combined scanner for PET and MRI to measure dopamine with the stimulant drug methylphenidate. Each scan will be done by getting a small amount of a radiotracer through an IV catheter. During each of the two PET/MRI scan sessions each subject will receive IV methylphenidate. We will look at the effects of methylphenidate on brain dopamine. We will also look at brain responses, mood and thinking. The results of each subject's scans will be compared to each other. We will also compare the results to other participants to see if we get similar information.","timeFrame":"We aim to have each subject (n=5) complete all study procedures within 60 days."},{"measure":"Part 2: Examine Tirzepatide s effects on subjective effects to MP,sleep, alcohol craving (AUD only), alcohol withdrawal symptoms (AUD only), food craving, locomotor activity, mood and weight.","description":"We will measure dopamine levels in the brain. Dopamine is a chemical messenger that carries signals between brain cells. It plays a role in human behavior. It is also believed to play a role in addiction. In this study, we will use a combined scanner for PET and MRI to measure dopamine with the stimulant drug methylphenidate. We will look at the effects of methylphenidate on brain dopamine. To do this we will obtain imaging scans after the subject receives Tirzepatide and a Placebo. We will also look at brain responses, mood and thinking. Results from the same scans on two separate days will be compared to each other. We will also compare the results to other participants to see if we get similar information.","timeFrame":"We aim to have each subject complete study procedures within 90 days, but this could take longer. AUD participants will undergo a Follow Up phone call about 1 month after imaging scans are complete."}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07559500"},{"nctId":"NCT07719933","title":"Intraoperative Continuous Terlipressin Infusion is Associated With Reduced Severe Postoperative Complications After Laparoscopic Hepatectomy: a Prospective Propensity Score-matched Cohort Study","officialTitle":"Intraoperative Continuous Terlipressin Infusion is Associated With Reduced Severe Postoperative Complications After Laparoscopic Hepatectomy: a Prospective Propensity Score-matched Cohort Study","summary":"Liver resection is an important surgical treatment for patients with liver diseases. Despite advances in surgical and anesthetic management, postoperative complications remain a major concern and may affect patient recovery. Maintaining stable blood circulation during surgery is an important part of perioperative care.\n\nTerlipressin is a vasoactive medication that may help maintain blood pressure and improve hemodynamic stability during surgery. However, the relationship between intraoperative continuous terlipressin infusion and postoperative outcomes after laparoscopic hepatectomy remains unclear.\n\nThis prospective observational cohort study aims to evaluate the association between continuous intraoperative terlipressin infusion and postoperative severe complications in patients undergoing laparoscopic hepatectomy.\n\nPatients undergoing laparoscopic hepatectomy at the First Affiliated Hospital of Sun Yat-sen University will be enrolled and followed according to a predefined study protocol. Perioperative clinical information, anesthetic management data, terlipressin exposure, and postoperative outcomes will be collected and analyzed. The primary outcome is the occurrence of severe postoperative complications, defined as Clavien-Dindo grade III or higher complications.","detailedDescription":"Liver resection is an important surgical procedure for the treatment of patients with various liver diseases. Although advances in surgical techniques and perioperative management have improved outcomes, postoperative complications remain a significant concern after major abdominal surgery. Perioperative hemodynamic management plays an important role in maintaining adequate organ perfusion and may influence postoperative recovery.\n\nTerlipressin is a vasoactive medication that increases vascular tone and may help maintain hemodynamic stability during surgery. In clinical practice, terlipressin may be administered during surgery based on the judgment of the attending anesthesiologist. However, the association between intraoperative continuous terlipressin infusion and postoperative outcomes in patients undergoing laparoscopic hepatectomy remains unclear.\n\nThis prospective observational cohort study was designed to evaluate the association between continuous intraoperative terlipressin infusion and postoperative severe complications in patients undergoing laparoscopic hepatectomy. Patients undergoing laparoscopic hepatectomy will be prospectively enrolled according to predefined eligibility criteria and followed according to the study protocol.\n\nClinical characteristics, perioperative management information, intraoperative terlipressin exposure, and postoperative outcomes will be collected prospectively. The primary objective of this study is to assess whether intraoperative continuous terlipressin infusion is associated with the incidence of severe postoperative complications after laparoscopic hepatectomy.","peptideSlugs":["vasopressin","terlipressin"],"peptideNames":["Vasopressin","Terlipressin"],"conditions":["Liver Neoplasms","Postoperative Complications"],"keywords":["Terlipressin","Laparoscopic hepatectomy","Liver resection","Postoperative complications","Retrospective cohort study","Pleural effusion"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"First Affiliated Hospital, Sun Yat-Sen University","slug":"first-affiliated-hospital-sun-yat-sen-university","class":"OTHER"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":161,"dates":{"start":"2024-04-01","primaryCompletion":"2024-12-31","completion":"2025-05-14","firstPosted":"2026-07-22","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["China"],"locations":[{"facility":"The First Affiliated Hospital of Sun Yat-sen University","status":null,"city":"Guangzhou","state":"Guangdong","country":"China","latitude":23.11667,"longitude":113.25}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adults aged 18 to 80 years\n* American Society of Anesthesiologists (ASA) physical status I-III\n* Scheduled for elective laparoscopic partial hepatectomy\n* Provided written informed consent\n\nExclusion Criteria:\n\n* Inability to tolerate the planned surgical procedure based on pre-anesthetic assessment\n* Severe hepatic dysfunction (Child-Pugh class B or higher)\n* Severe renal dysfunction (blood urea nitrogen \\> 9 mmol/L or serum creatinine \\> 178 μmol/L)\n* Significant cardiovascular or cerebrovascular disease, including active coronary artery disease, severe valvular stenosis, hypertrophic obstructive cardiomyopathy, or history of extensive cerebral infarction\n* Known allergy to study medications\n* Body mass index (BMI) \\> 35 kg/m² or \\< 18 kg/m²\n* Hemoglobin level \\< 90 g/L\n* Pregnancy or lactation\n* Participation in another clinical trial within the preceding 3 months\n* Any other condition considered inappropriate for study participation by the investigator","minimumAge":"18 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"terlipressin","description":"Terlipressin is a vasopressin analogue used for perioperative hemodynamic management. In this prospective observational cohort study, continuous intraoperative terlipressin infusion was administered during laparoscopic hepatectomy according to the clinical judgment of the attending anesthesiologist. The use of terlipressin was based on routine clinical practice and was not assigned or mandated by the study protocol."}],"primaryOutcomes":[{"measure":"Incidence of severe postoperative complications","description":"Severe postoperative complications will be defined as Clavien-Dindo grade III or higher complications occurring after laparoscopic hepatectomy.","timeFrame":"Within 30 days after surgery"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07719933"},{"nctId":"NCT07728669","title":"Digital Dietary Intervention for Patients Receiving GLP-1 Receptor Agonist Therapy","officialTitle":"Efficacy of a Digital Dietary Intervention (NutriSteppe Application) in Improving Metabolic Parameters in Adults With Type 2 Diabetes Mellitus, Obesity or Overweight With Comorbidities Who Are Receiving GLP-1 Receptor Agonist Therapy and Other Medications Prescribed Under Routine Clinical Protocols","summary":"The goal of this clinical trial is to learn whether adding the NutriSteppe digital dietary intervention to routine medical care improves metabolic health in adults aged 21 to 65 years with type 2 diabetes mellitus, obesity, or overweight with related health conditions. Participants are already receiving or have been prescribed glucagon-like peptide-1 (GLP-1) receptor agonist therapy by their treating physicians outside the study.\n\nThe main question is:\n\nDoes the NutriSteppe digital dietary intervention improve glycated hemoglobin (HbA1c), a measure of average blood glucose, after 12 weeks compared with routine medical care alone?\n\nThe study will also assess changes in fasting blood glucose, body weight, body mass index, waist circumference, cholesterol, triglycerides, blood pressure, diet quality, quality of life, dietary adherence, and safety.\n\nResearchers will randomly assign participants to one of two groups. The control group will continue routine medical care and receive general lifestyle advice. The intervention group will continue routine medical care and use the NutriSteppe application for 12 weeks to receive personalized dietary support.\n\nParticipants in both groups will:\n\n* Attend study visits and complete the examinations, laboratory tests, and questionnaires specified in the study protocol.\n* Photograph everything they eat and drink.\n* Have their food photographs automatically analyzed using Tagam-AI, a system developed for this study.\n* Be able to view the results of the food photograph analysis.\n\nThe photography and automated analysis procedures will be the same in both groups. Only participants in the intervention group will receive personalized dietary recommendations generated from these data through the NutriSteppe application.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Type 2 Diabetes Mellitus (T2DM)","Obesity (Disorder)","Overweight","Metabolic Syndrome"],"keywords":["NutriSteppe","Digital Dietary Intervention","Personalized Nutrition","GLP-1 Receptor Agonist","Semaglutide","Glycated Hemoglobin","HbA1c","Continuous Glucose Monitoring"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Kazakh Academy of Nutrition","slug":"kazakh-academy-of-nutrition","class":"OTHER"},"collaborators":[{"name":"Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan","slug":"science-committee-of-the-ministry-of-science-and-higher-education-of-the-republic-of-kazak","class":"UNKNOWN"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":120,"dates":{"start":"2026-07-20","primaryCompletion":"2026-11","completion":"2027-01","firstPosted":"2026-07-27","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["Kazakhstan"],"locations":[{"facility":"Kazakh Academy of Nutrition LLP","status":"RECRUITING","city":"Almaty","state":null,"country":"Kazakhstan","latitude":43.25249,"longitude":76.9115}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 21-65 years inclusive at the time of signing informed consent.\n* Male or female.\n* Overweight with at least one comorbidity, including diabetes mellitus; arterial hypertension of at least 130/85 mmHg or use of antihypertensive medication; dyslipidemia defined as triglycerides of at least 1.7 mmol/L, reduced HDL cholesterol below 1.0 mmol/L in men or below 1.3 mmol/L in women, or use of lipid-lowering medication; cardiovascular disease; respiratory or joint disease; non-alcoholic fatty liver disease; sleep disorders; or other comorbidities.\n* For participants with overweight: body mass index of 25.0-29.9 kg/m² for the Caucasian population or 23.0-27.4 kg/m² for the Asian population, together with abdominal obesity defined as waist circumference of at least 94 cm in men and 80 cm in women of the European population, or at least 90 cm in men and 80 cm in women of the Asian population.\n* Class I-III obesity where diet combined with physical activity has been ineffective, defined as weight loss of less than 5% over 3 months.\n* Class I obesity: body mass index of 30.0-34.9 kg/m² for the Caucasian population or 27.5-32.4 kg/m² for the Asian population.\n* Class II obesity: body mass index of 35.0-39.9 kg/m² for the Caucasian population or 32.5-37.4 kg/m² for the Asian population.\n* Type 2 diabetes mellitus with HbA1c of at least 6.5% (48 mmol/mol), fasting glucose of at least 6.1 mmol/L in capillary whole blood or at least 7.0 mmol/L in venous plasma, glucose of at least 11.1 mmol/L two hours after an oral glucose tolerance test, or random glucose of at least 11.1 mmol/L.\n* Body mass index of at least 25 kg/m² and no more than 40 kg/m² at screening.\n* Already receiving, or prescribed, GLP-1 receptor agonist therapy with semaglutide by the treating physician independently of the study. The study does not prescribe or modify this therapy.\n* Stable doses of medications for chronic conditions, including antihypertensive agents and statins, for at least 8 weeks before screening.\n* Ownership of an iOS or Android smartphone with internet access and willingness to download and use the \"NutriSteppe\" application if assigned to the intervention group.\n* Ability and willingness to provide written informed consent and comply with study procedures.\n* Women of childbearing potential must use effective contraception throughout the study.\n\nExclusion Criteria:\n\n* Diagnosis of type 1 diabetes mellitus.\n* History of diabetic ketoacidosis or hyperglycemic hyperosmolar state.\n* Initiation of GLP-1 receptor agonist therapy less than 4 weeks before screening.\n* Current insulin therapy.\n* Personal or family history of medullary thyroid carcinoma.\n* Personal history of multiple endocrine neoplasia type 2 (MEN2).\n* History of acute or chronic pancreatitis.\n* Active gallbladder disease or history of gallbladder disease within 6 months before screening.\n* Severe gastrointestinal disease, including gastroparesis.\n* Major cardiovascular event within 6 months before screening, including myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass grafting, or percutaneous coronary intervention.\n* Uncontrolled arterial hypertension, defined as systolic blood pressure above 160 mmHg or diastolic blood pressure above 100 mmHg at screening.\n* Chronic kidney disease with an estimated glomerular filtration rate below 30 mL/min/1.73 m² using the MDRD or CKD-EPI formula.\n* Severe hepatic impairment classified as Child-Pugh class C, or ALT or AST greater than three times the upper limit of normal.\n* Active malignancy or history of malignancy within 5 years, except successfully treated basal cell or squamous cell carcinoma of the skin.\n* Established HIV infection, active hepatitis B defined as HBsAg positive with detectable HBV DNA, or hepatitis C virus infection.\n* History of bariatric surgery or bariatric surgery planned during the study.\n* Anorexia nervosa, bulimia nervosa, or binge eating disorder diagnosed or active within the past year.\n* Pregnancy or breastfeeding.\n* Planning pregnancy during the study.\n* Woman of childbearing potential unwilling to use effective contraception.\n* Use of weight-loss medication, including orlistat, phentermine, combinations with topiramate, naltrexone-bupropion, or other weight-loss medication within 3 months before screening.\n* Use of systemic corticosteroids, excluding inhaled or topical corticosteroids, for more than 2 weeks within 3 months before screening.\n* Use of antipsychotic medication associated with significant weight gain unless used at a stable dose for more than 6 months.\n* Participation in another interventional clinical study within 30 days before screening.\n* Known hypersensitivity to semaglutide or any excipient.\n* No smartphone or unwillingness to use digital health technology.\n* Severe mental disorder impairing the ability to provide informed consent or comply with the protocol.\n* Active alcohol or drug dependence within the past year.\n* Any condition that, in the investigator's opinion, may compromise participant safety or the integrity of the study.","minimumAge":"21 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"BEHAVIORAL","name":"NutriSteppe Digital Dietary Intervention","description":"The NutriSteppe mobile application provides personalized meal planning, a food diary, nutritional analysis, dietary goals, educational modules, culturally adapted recipes, progress monitoring, reminders, and dietary recommendations intended to support metabolic health and food tolerance during GLP-1 receptor agonist therapy. Participants use the application for 12 weeks, complete the food diary at least 5 days per week, record body weight weekly, review dietary suggestions, and complete weekly educational modules."}],"primaryOutcomes":[{"measure":"Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12","description":"HbA1c will be measured as a percentage at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value. A negative change indicates a reduction in HbA1c.","timeFrame":"Baseline and Week 12"}],"secondaryOutcomes":[{"measure":"Change From Baseline in Fasting Plasma Glucose at Week 12","description":"Fasting plasma glucose will be measured in mmol/L at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value. A negative change indicates a reduction in fasting plasma glucose.","timeFrame":"Baseline and Week 12"},{"measure":"Proportion of Participants Achieving HbA1c Below 6.5% at Week 12","description":"The proportion of participants with glycated hemoglobin (HbA1c) below 6.5% at week 12 will be calculated as the number of participants meeting this threshold divided by the number of participants assessed.","timeFrame":"Week 12"},{"measure":"Change From Baseline in Body Weight at Week 12","description":"Body weight will be measured in kilograms at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value. A negative change indicates weight loss.","timeFrame":"Baseline and Week 12"},{"measure":"Percentage Change From Baseline in Body Weight at Week 12","description":"Percentage change in body weight will be calculated as the difference between body weight at week 12 and baseline body weight, divided by baseline body weight and multiplied by 100. A negative value indicates weight loss.","timeFrame":"Baseline and Week 12"},{"measure":"Proportion of Participants Achieving at Least 5% Weight Loss at Week 12","description":"The proportion of participants whose body weight decreases by at least 5% from baseline to week 12 will be calculated.","timeFrame":"Baseline and Week 12"},{"measure":"Change From Baseline in Body Mass Index at Week 12","description":"Body mass index will be calculated in kg/m² at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value. A negative change indicates a reduction in body mass index.","timeFrame":"Baseline and Week 12"},{"measure":"Change From Baseline in Waist Circumference at Week 12","description":"Waist circumference will be measured in centimeters at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value. A negative change indicates a reduction in waist circumference.","timeFrame":"Baseline and Week 12"},{"measure":"Change From Baseline in LDL Cholesterol at Week 12","description":"Low-density lipoprotein cholesterol will be measured in mmol/L at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value.","timeFrame":"Baseline and Week 12"},{"measure":"Change From Baseline in HDL Cholesterol at Week 12","description":"High-density lipoprotein cholesterol will be measured in mmol/L at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value.","timeFrame":"Baseline and Week 12"},{"measure":"Change From Baseline in Total Cholesterol at Week 12","description":"Total cholesterol will be measured in mmol/L at baseline and at week 12. Change will be calculated as the week 12 value minus the baseline value.","timeFrame":"Baseline and Week 12"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07728669"},{"nctId":"NCT07730151","title":"Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer.","officialTitle":"Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer: A Multicenter, Prospective, Randomized Controlled Study","summary":"The goal of this study is to evaluate the efficacy and safety of darolutamide combined with docetaxel and ADT compared to docetaxel combined with ADT in treating locally advanced prostate cancer patients scheduled for radical prostatectomy. The participant population includes adult males with locally advanced prostate cancer (cT3b-cT4, N0, M0 or any cT, N1, M0). The main questions it aims to answer are:\n\nDoes the combination of darolutamide, docetaxel, and ADT improve treatment outcomes compared to docetaxel combined with ADT? What are the safety profiles and adverse effects associated with each treatment group? Researchers will compare the control group (docetaxel combined with ADT) to the experimental group (darolutamide combined with docetaxel and ADT) to see if the experimental treatment is more effective.\n\nParticipants will:\n\nReceive either docetaxel combined with ADT or darolutamide combined with docetaxel and ADT for 4 cycles (16 weeks) as neoadjuvant treatment.\n\nUndergo radical prostatectomy after completing the neoadjuvant treatment. Be followed up for 36 months post-surgery to assess treatment efficacy and safety.","detailedDescription":null,"peptideSlugs":["goserelin","triptorelin","leuprolide"],"peptideNames":["Goserelin","Triptorelin","Leuprolide"],"conditions":["Prostate Cancer","Prostate","Prostate Cancer Patients"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"RenJi Hospital","slug":"renji-hospital","class":"OTHER"},"collaborators":[{"name":"Bayer","slug":"bayer","class":"INDUSTRY"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":200,"dates":{"start":"2026-08-01","primaryCompletion":"2031-12-31","completion":"2031-12-31","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Male, age \\>= 18 years and \\<= 75 years at the time of signing the informed consent form;\n2. Confirmed as prostate cancer by histological or cytological examination, and planned for radical prostatectomy;\n3. Clinical stage conforms to the definition of locally advanced prostate cancer: cT3b-cT4, N0, M0 or any cT, N1, M0 (based on PSMA-PET/CT examination);\n4. Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;\n5. Expected lifespan \\>= 10 years;\n6. Important laboratory indicators meet the following requirements: a. Hemoglobin \\>= 90 g/L b. Serum total bilirubin \\<= 1.5 times the upper limit of normal value, transaminase (AST/ALT) \\<= 2.5 times the upper limit of normal value c. Serum albumin \\>= 30 g/L d. Serum creatinine \\<= 1.5 times the upper limit of normal value e. Absolute neutrophil count \\>= 1.5 x 10\\^9/L, platelet count \\>= 100 x 10\\^9/L;\n7. No difficulty in swallowing (can take the medicine in whole), chronic diarrhea, intestinal obstruction or other factors affecting drug administration and absorption;\n8. No use of opioid analgesics (including codeine, oxycodone, etc.) to relieve cancer pain;\n9. If the spouse is a fertile female, the subject consents to take effective contraceptive measures during the treatment period and for 4 months after the surgery;\n10. The subject voluntarily participates in this trial, signs the informed consent form, and is willing to comply with the requirements of the research protocol throughout the study period.\n\nExclusion Criteria:\n\n1. Pathological diagnosis of neuroendocrine prostate cancer, including small cell carcinoma;\n2. Prior local or systemic treatment for prostate cancer, including but not limited to radiotherapy, chemotherapy, or endocrine therapy;\n3. Confirmed bone metastasis, hepatic metastasis, brain metastasis, or other visceral metastases on imaging;\n4. Known hypersensitivity to the study drugs (active ingredients or excipients) or drugs of the same class;\n5. Contraindications to prednisone acetate or docetaxel, such as active infection, allergy, or other conditions;\n6. Chronic disease requiring prednisone acetate at doses exceeding those specified in the protocol (5 mg orally twice daily, starting 14 days before docetaxel chemotherapy and stopping 3 weeks after the last chemotherapy cycle);\n7. Poorly controlled hypertension despite medication (systolic blood pressure \\>=160 mmHg or diastolic blood pressure \\>=95 mmHg);\n8. Active or symptomatic viral hepatitis or other chronic liver disease; known human immunodeficiency virus (HIV) infection;\n9. History of pituitary or adrenal dysfunction;\n10. Active autoimmune disease requiring hormonal therapy;\n11. Major cardiovascular or cerebrovascular disease within 6 months prior to the start of study treatment, including: severe/unstable angina, myocardial infarction, congestive heart failure \\[New York Heart Association (NYHA) class III or above\\], cerebrovascular accident, or arrhythmia requiring pharmacological treatment;\n12. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;\n13. Grade ≥2 peripheral sensory or motor neuropathy;\n14. Other malignancies occurring within the past 2 years or currently concurrent malignancies;\n15. Major surgery requiring general anesthesia within 28 days before the first dose;\n16. Treatment with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole) or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St. John's wort) that cannot be discontinued, and have not been stopped for at least 7 days before randomization;\n17. History of epilepsy;\n18. Alcohol or drug abuse or dependence;\n19. Participation in another therapeutic clinical study within 1 month before the start of study treatment;\n20. Any other condition that the investigator considers unsuitable for participation in this study;","minimumAge":"18 Years","maximumAge":"75 Years","sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Darolutamide","description":"Darolutamide: oral administration, 600 mg per dose, twice daily, taken with food."},{"type":"DRUG","name":"docetaxel","description":"Docetaxel: intravenous injection, 75 mg/m², once every 3 weeks, for a total of 4 doses/cycles. (Oral prednisone acetate should be started 14 days before docetaxel chemotherapy at 5 mg twice daily and discontinued 3 weeks after the last chemotherapy cycle.)"},{"type":"DRUG","name":"ADT","description":"ADT: leuprorelin, goserelin, or triptorelin, selected by the investigator according to the patient's condition, administered by subcutaneous or intramuscular injection, using a once-monthly formulation uniformly."}],"primaryOutcomes":[{"measure":"3-year biochemical progression-free survival (bPFS)","description":null,"timeFrame":"Every 3 months (±14 days) up to 36 months after surgery"}],"secondaryOutcomes":[{"measure":"Pathological Downstaging Rate after Radical Prostatectomy","description":null,"timeFrame":"On Surgery day"},{"measure":"Incidence of Treatment-Related Adverse Events","description":null,"timeFrame":"From screening visit to 30 days after the last neoadjuvant dose or start of new anticancer therapy"},{"measure":"Time to Castration-Resistant Prostate Cancer (CRPC) at 3 Years","description":null,"timeFrame":"every 3 months PSA tests and every 6 months imaging assessments up to 36 months after surgery"},{"measure":"Objective Response Rate (ORR)","description":null,"timeFrame":"2-4 weeks after completion of neoadjuvant therapy"},{"measure":"3-year Radiographic Progression-Free Survival (rPFS)","description":null,"timeFrame":"Every 6 months (±1 month) post-surgery until 36 months post-surgery (months 6, 12, 18, 24, 30, 36)"},{"measure":"Undetectable PSA Rate post-Radical Prostatectomy","description":null,"timeFrame":"6 weeks post-surgery (±7 days)"},{"measure":"Subject Quality of Life as assessed by FACT-P( Functional Assessment of Cancer Therapy - Prostate) scale","description":"The FACT-P(Functional Assessment of Cancer Therapy - Prostate) scale will be used to assess the quality of life of subjects. The total score is calculated from the general functional and prostate cancer-specific subscale scores, with a total score range of 0 to 156, where higher scores indicate better functional status. Changes in the total score and individual domain scores will be analyzed.","timeFrame":"Baseline (V0), post-neoadjuvant/pre-surgery (V5), and at 6, 12, 24, 36 months post-surgery (±14 days)"},{"measure":"Perioperative Complications","description":null,"timeFrame":"From surgery date through 90 days post-surgery"},{"measure":"Positive Surgical Margin Rate after Radical Prostatectomy","description":null,"timeFrame":"On surgery day"},{"measure":"3-year biochemical progression-free survival (bPFS)","description":null,"timeFrame":"Every 3 months (±14 days) up to 36 months after surgery"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07730151"},{"nctId":"NCT07730294","title":"Evaluating Intranasal Oxytocin (TNX-1900) for Pain Relief and Recovery After Pituitary Surgery","officialTitle":"Investigating the Effect of TNX-1900 on Pain Management, Neural and Socio-Emotional Functioning in Patients Undergoing Pituitary Surgery","summary":"This study is testing whether oxytocin can help lessen pain by changing how people process emotions and social experiences. The goal is to better understand how the brain links emotions, relationships, and pain, and whether this connection can be used to improve pain treatment.","detailedDescription":"This study employs a randomized, double-blind, placebo-controlled design to evaluate the efficacy of an intranasal oxytocin formulation, TNX-1900, on pain management, neural functioning, and socio-emotional health in patients undergoing pituitary surgery. Participants will be randomized into 3 groups: One group will receive low-dose oxytocin (6 IU), one group will receive high-dose oxytocin (24 IU), and one group will receive a matching placebo formulation. Participants will administer their nasal spray (blinded) daily for 7 days leading up to, and including the day of surgery, and 7 days following the surgery. Assessments (surveys and EEG/ERP) will be included throughout the protocol.","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["Pain","Pituitary Surgery"],"keywords":["pain","pain perception","oxytocin","intranasal"],"conditionGroups":[{"slug":"pain","label":"Pain"}],"sponsor":{"name":"Yale University","slug":"yale-university","class":"OTHER"},"collaborators":[{"name":"Tonix Pharmaceuticals, Inc.","slug":"tonix-pharmaceuticals-inc","class":"INDUSTRY"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":75,"dates":{"start":"2026-08","primaryCompletion":"2028-08","completion":"2028-08","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Yale University","status":null,"city":"New Haven","state":"Connecticut","country":"United States","latitude":41.30815,"longitude":-72.92816}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age: Between 30 to 75 years old.\n* Consent: Ability to give informed consent.\n* Language: Proficiency in the English language.\n* Medical Condition: Diagnosed with a pituitary lesion requiring surgery.\n* Menopausal Status: Post-menopause for women (at least 1 year since last menstrual period).\n\nExclusion Criteria:\n\n* Medication: Individuals on stable doses of psychotropic medication for at least the past six weeks are eligible, excluding those with changes in medication within that timeframe.\n* Neurological Conditions: A history of seizures, current use of anticonvulsants.\n* Pregnancy: Currently pregnant, currently lactating, or up to 1-year post partum.\n* Any history of renal impairment (serum creatinine \\>1.2 x ULN)\n* Any history of hepatic impairment (AST and/or ALT \\>2 x ULN)\n* Surgical History: Any history of previous pituitary surgery procedures\n* Subjects who require 24-hour coverage with NSAIDs, e.g., arthritis, should not be included in the study.\n* Any known hypersensitivity to TNX-1900","minimumAge":"30 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Oxytocin (Low dose)","description":"The dosage for low -dose intranasal oxytocin is set at 6 International Units (IU) per day, divided into two administrations of 3IU each per nostril. The administration begins one week prior to surgery, continues on the day of the surgery, and extends through the week following the surgery."},{"type":"DRUG","name":"Oxytocin (High dose)","description":"The dosage for high-dose intranasal oxytocin is set at 24 International Units (IU) per day, divided into two administrations of 12 IU each per nostril. The administration begins one week prior to surgery, continues on the day of the surgery, and extends through the week following the surgery."},{"type":"DRUG","name":"Placebo (saline)","description":"Placebo nasal spray (no study medication, magnesium only). The administration begins one week prior to surgery, continues on the day of the surgery, and extends through the week following the surgery."}],"primaryOutcomes":[{"measure":"Change in post-operative pain measured by the Numeric Pain Rating Scale (NPRS)","description":"The NPRS is a patient-reported tool used to assess pain intensity on a scale from 0 (no pain) to 10 (worst possible pain).","timeFrame":"Pre-op up to 8 weeks after last drug administration"},{"measure":"Change in post-operative pain measured by monitoring of pain medication usage","description":"Daily pain medication usage will be reported by participants leading up to surgery and after discharge. Daily pain medication usage will be reported through the participant's medical record during surgery and inpatient stay.","timeFrame":"Pre-op up to 8 weeks after last drug administration"}],"secondaryOutcomes":[{"measure":"Changes in participant reported depression as measured by the Beck Depression Inventory (BDI-II)","description":"BDI-II is a 21-item patient-reported questionnaire used to assess the severity of depressive symptoms. Total scores range from 0 to 63, with higher scores indicating more severe depression.","timeFrame":"Pre-op up to 8 weeks after last drug administration"},{"measure":"Changes in participant reported anxiety as measured by the Beck Anxiety Inventory (BAI)","description":"BAI is a 21-item patient-reported questionnaire used to assess the severity of anxiety symptoms. Total scores range from 0 to 63, with higher scores indicating more severe anxiety.","timeFrame":"Pre-op up to 8 weeks after last drug administration"},{"measure":"Changes in participant reported anxiety as measured by the Generalized Anxiety Disorder-7","description":"GAD-7 is a 7-item patient-reported questionnaire used to assess the severity of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating more severe anxiety.","timeFrame":"Pre-op up to 8 weeks after last drug administration"},{"measure":"Changes in participant reported depression as measured by the Patient Health Questionnaire-9","description":"PHQ-9 is a 9-item patient-reported questionnaire used to assess the severity of depressive symptoms. Total scores range from 0 to 27, with higher scores indicating more severe depression.","timeFrame":"Pre-op up to 8 weeks after last drug administration"},{"measure":"Change in neural functioning measured by Electroencephalography (EEG)/Event-Related Potential (ERP)","description":"EEG/ERP sessions are done at specific intervals to look at delta-beta neural oscillations and N170, P300, and LPP ERPs elicited by social and emotional stimuli (photos of faces and houses).","timeFrame":"Pre-op and the last day of drug administration, approximately 14 days"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07730294"},{"nctId":"NCT07731256","title":"Semaglutide for Low Back Pain","officialTitle":"A Randomized-Controlled Trial of Semaglutide for Patients With Chronic Low Back Pain and Obesity","summary":"Low back pain is the leading cause of disability in the United States, and obesity is a major risk factor for its development. GLP-1 receptor agonists such as Semaglutide have emerged as effective weight loss agents that may also reduce chronic pain through weight reduction and other mechanisms. This randomized, double-blind, placebo-controlled trial will enroll 250 adults with chronic low back pain and obesity, randomized 1:1 to weekly Semaglutide 2.4 mg or placebo for 52 weeks. The primary outcome is change in low back pain severity, with secondary outcomes including pain-related disability and quality of life.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Lower Back Pain","Obesity (BMI>30)","Chronic Lower Back Pain","glp1 Agonist"],"keywords":["Lower back pain","Obesity","Chronic Lower Back Pain","GLP1 Agonist"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"pain","label":"Pain"}],"sponsor":{"name":"Washington University School of Medicine","slug":"washington-university-school-of-medicine","class":"OTHER"},"collaborators":[{"name":"Novo Nordisk","slug":"novo-nordisk","class":"INDUSTRY"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":250,"dates":{"start":"2027-02-01","primaryCompletion":"2031-01-01","completion":"2031-09-01","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"The University of Alabama at Birmingham","status":null,"city":"Birmingham","state":"Alabama","country":"United States","latitude":33.52066,"longitude":-86.80249},{"facility":"Washington University School of Medicine","status":null,"city":"St Louis","state":"Missouri","country":"United States","latitude":38.62727,"longitude":-90.19789}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Ability to provide informed consent before any trial-related activities\n* Age: 18-85 years\n* Chronic low back pain, defined as an average low back pain severity of at least 4/10 present on most days for 3 months or longer.\n* BMI: 30-49 kg/m2\n\nExclusion Criteria:\n\n* Known or suspected allergy to trial medication(s), excipients, or related products\n* Contraindications to study medication(s), worded specifically as stated in the product's Prescribing Information\n* Previous randomization in this trial\n* Pregnant, breastfeeding, or the intention of becoming pregnant or not using adequate contraceptive measures\n* Low back pain related to infection, trauma, or malignancy\n* Plans to undergo new back pain interventions within 3 months.\n* Considering or have been offered surgery to treat structural disease believed to cause their low back pain, including infection, severe degeneration adjacent to a prior fusion, mobile spondylolisthesis, severe central lumbar stenosis, coronal or sagittal deformity, or other severe structural pathology diagnosed by a board-certified spine surgeon. Ambiguous cases will be adjudicated by a board-certified spine surgeon.\n* Another source of pain that is more severe than their low back pain (e.g., headache or radiculopathy)\n* History of or plans to undergo bariatric weight loss surgery\n* History of a major abdominal or stomach surgery that might affect drug absorption\n* Decrease in body weight of \\> 5 kg within 3 months of screening\n* History of diabetes mellitus, with HbA1c \\> 7 or requiring medical treatment (i.e., insulin or other diabetes medication other than Metformin).\n* Uncontrolled hypertension, defined as a systolic blood pressure (BP) \\> 155 mmHg or a diastolic BP \\> 100 mmHg\n* Clinically significant congestive heart failure, defined as New York Heart Association Class IV, or active symptoms related to heart failure, or exacerbation requiring hospitalization within 90 days of screening.\n* Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris, or transient ischemic attack within 90 days of screening.\n* Other medical conditions that could impact their treatment, similar to prior published reports\n* Treatment with oral or injectable glucagon-like peptide-1 (GLP-1) receptor agonists within 3 months before screening\n* Active acute or chronic pancreatitis diagnosed within 180 days or history of unprovoked pancreatitis within the past year.\n* Stage 3 or worse chronic kidney disease (i.e., eGFR \\< 60).\n* Known active gallstone disease, other than disease previously treated with cholecystectomy.\n* Newly diagnosed or worsening chronic liver disease.\n* Active malignancy\n* Major neurological disease, such as multiple sclerosis or Parkinson's Disease\n* Major psychiatric disease, such as psychosis or schizophrenia, or a psychiatric disease requiring hospitalization in the preceding 12 months\n* History of a suicide attempt or any reported suicidal behavior reported within 30 days of screening.\n* Personal history of MEN2\n* Personal or family history of medullary thyroid cancer\n* Impaired sensorium due to alcohol or drug use.","minimumAge":"18 Years","maximumAge":"85 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide (administered by PDS290 pen-injector)","description":"Semaglutide 3.0 mg/mL solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals. Dose escalation: 0.24 mg weekly for 28 days, then increased to 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg every 4 weeks to reach the maintenance dose of 2.4 mg. The pen uses a drum scale of 1-80 (in increments of 1); corresponding dose counter values are: 0.24 mg = 8, 0.5 mg = 17, 1.0 mg = 34, 1.7 mg = 57, 2.4 mg = 80. Treatment duration is 52 weeks."},{"type":"DRUG","name":"Placebo (administered by PDS290 pen-injector)","description":"Matching placebo solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals, following the same escalating dose counter schedule as the active comparator (counter values: 8, 17, 34, 57, 80 every 4 weeks). Treatment duration is 52 weeks."}],"primaryOutcomes":[{"measure":"BPI-SF Pain Severity Scale","description":"The primary endpoint will be change in low back pain severity, measured using the 0-10 BPI-SF Pain Severity Scale. This outcome will be compared in the treatment group versus placebo.","timeFrame":"Baseline, up to 52 weeks"}],"secondaryOutcomes":[{"measure":"BPI-SF Pain Interference","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"Oswestry Disability Index (ODI)","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"PROMIS Depression","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"Pain Catastrophizing Scale","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"Insomnia Severity Index","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"PROMIS Sleep Disturbance","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"Waist Circumference","description":null,"timeFrame":"Baseline, up to 52 weeks"},{"measure":"Number of New Concomitant Back Pain Treatments","description":"The number and type of new low back pain treatments initiated during the study period, captured using the study's Concomitant Back Pain Treatment Log.\n\nNew daily pain medications, exercise/therapy regimens, cognitive/behavioral interventions, spinal injections, interventional pain procedures, lumbar spine surgery, and other treatments.","timeFrame":"Baseline, up to 52 weeks"},{"measure":"Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP)","description":"Serum hs-CRP will be measured at each time point and reported in mg/L. Additional exploratory inflammatory blood biomarkers may also be assessed to characterize systemic inflammation.","timeFrame":"Baseline, every 6 months till 52 weeks."}],"publications":[{"pmid":"32520773","citation":"Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, Rowbotham MC, Bhagwagar Z, Burke LB, Cowan P, Ellenberg SS, Evans SR, Freeman RL, Garrison LP, Iyengar S, Jadad A, Jensen MP, Junor R, Kamp C, Katz NP, Kesslak JP, Kopecky EA, Lissin D, Markman JD, Mease PJ, O'Connor AB, Patel KV, Raja SN, Sampaio C, Schoenfeld D, Singh J, Steigerwald I, Strand V, Tive LA, Tobias J, Wasan AD, Wilson HD. Interpretation of chronic pain clinical trial outcomes: IMMPACT recommended considerations. Pain. 2020 Nov;161(11):2446-2461. doi: 10.1097/j.pain.0000000000001952."},{"pmid":"34051018","citation":"van Lennep JHPA, Trossel F, Perez RSGM, Otten RHJ, van Middendorp H, Evers AWM, Szadek KM. Placebo effects in low back pain: A systematic review and meta-analysis of the literature. Eur J Pain. 2021 Oct;25(9):1876-1897. doi: 10.1002/ejp.1811. Epub 2021 Jun 21."},{"pmid":"37385275","citation":"Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)01200-X. Epub 2023 Jun 26."},{"pmid":"28192789","citation":"Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians; Denberg TD, Barry MJ, Boyd C, Chow RD, Fitterman N, Harris RP, Humphrey LL, Vijan S. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Apr 4;166(7):514-530. doi: 10.7326/M16-2367. Epub 2017 Feb 14."},{"pmid":"35507483","citation":"Chiarotto A, Koes BW. Nonspecific Low Back Pain. N Engl J Med. 2022 May 5;386(18):1732-1740. doi: 10.1056/NEJMcp2032396. No abstract available."},{"pmid":"8080219","citation":"Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38."},{"pmid":"40016636","citation":"He Y, Xu B, Zhang M, Chen D, Wu S, Gao J, Liu Y, Zhang Z, Kuang J, Fang Q. Advances in GLP-1 receptor agonists for pain treatment and their future potential. J Headache Pain. 2025 Feb 27;26(1):46. doi: 10.1186/s10194-025-01979-4."},{"pmid":"39301951","citation":"Samajdar SS, Bhaduri G, Ghoshal PK, Mukherjee S, Pal J, Chatterjee N, Joshi SR. Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes. Pain Manag. 2024;14(7):365-373. doi: 10.1080/17581869.2024.2402214. Epub 2024 Sep 20."},{"pmid":"39808758","citation":"Emmerich SD, Fryar CD, Stierman B, Ogden CL. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief. 2024 Sep;(508):10.15620/cdc/159281. doi: 10.15620/cdc/159281."},{"pmid":"20007994","citation":"Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain: a meta-analysis. Am J Epidemiol. 2010 Jan 15;171(2):135-54. doi: 10.1093/aje/kwp356. Epub 2009 Dec 11."},{"pmid":"27537761","citation":"Jackson T, Thomas S, Stabile V, Shotwell M, Han X, McQueen K. A Systematic Review and Meta-Analysis of the Global Burden of Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: Trends in Heterogeneous Data and a Proposal for New Assessment Methods. Anesth Analg. 2016 Sep;123(3):739-48. doi: 10.1213/ANE.0000000000001389."},{"pmid":"39833406","citation":"Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 Mar;31(3):951-962. doi: 10.1038/s41591-024-03412-w. Epub 2025 Jan 20."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07731256"},{"nctId":"NCT07732218","title":"Efficacy of Once Weekly Semaglutide in Patients With Type 2 Diabetes: a Non Randomized Clinical Trial","officialTitle":"Efficacy of Once Weekly Semaglutide in Patients With Type 2 Diabetes: a Non Randomized Clinical Trial","summary":"A single arm no randomized clinical trial evaluated the effectiveness and safety of once weekly semaglutide in adults with type 2 diabetes militus and obesity whose glycemic control remained inadequate despite standard therapy. participants received semaglutide for 16 weeks, beginning with 0.25mg weekly for 4 weeks followed by 0.5 mg weekly for 12 weeks. the primary outcome was the change in glycated hemoglobin, while secondary outcomes included changes in body weight, body mass index, blood glucose, blood pressure, lipid profile and treatment related adverse effects.","detailedDescription":"This single-arm, non-randomized, off-label clinical trial evaluated the efficacy and safety of once-weekly semaglutide in adults with type 2 diabetes mellitus and obesity who had inadequate glycemic control despite receiving standard glucose-lowering therapy. The study was conducted at two diabetes care centers in Peshawar, Pakistan, between July 2022 and March 2023. The protocol was approved by the Institutional Review Board of Rehman Medical Institute, Peshawar, and written informed consent was obtained from all participants before enrollment.\n\nAdults aged 18 years or older were eligible if they had established type 2 diabetes mellitus for at least six months, glycated hemoglobin levels between 7.5% and 10.0%, and a body mass index of at least 30 kg/m² despite ongoing diabetes treatment. Participants were excluded if they had type 1 diabetes mellitus, gestational diabetes, severe renal impairment, previous or current treatment with a glucagon-like peptide-1 receptor agonist, chronic pancreatitis, pancreatic malignancy, diabetic retinopathy requiring active treatment, significant ocular complications, pregnancy, lactation, or known thyroid disease or thyroid neoplasms.\n\nEligible participants received subcutaneous semaglutide once weekly for a total treatment period of 16 weeks. Semaglutide was initiated at a dose of 0.25 mg once weekly for the first four weeks and was then increased to 0.5 mg once weekly for the following 12 weeks. Participants who were taking dipeptidyl peptidase-4 inhibitors discontinued those medications before starting semaglutide. Other background glucose-lowering medications, including metformin, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, and basal insulin, were continued at the discretion of the treating physician unless clinical adjustment was required.\n\nAll participants received standardized counseling regarding dietary modification, physical activity, medication adherence, injection technique, and the recognition and management of possible adverse effects. Treatment adherence was assessed during follow-up through participant interviews and inspection of used injection pens.\n\nBaseline demographic and clinical data included age, sex, duration of diabetes, body weight, height, body mass index, fasting blood glucose, random blood glucose, glycated hemoglobin, systolic and diastolic blood pressure, and lipid profile. Participants attended a follow-up visit at four weeks to assess adherence, dose escalation, tolerability, and adverse events. At the end of the 16-week treatment period, the baseline clinical and biochemical measurements were repeated.\n\nThe primary outcome was the change in glycated hemoglobin from baseline to 16 weeks. Secondary outcomes included changes in body weight, body mass index, fasting blood glucose, random blood glucose, systolic and diastolic blood pressure, and lipid profile. Treatment-related adverse events were also recorded throughout the study.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Type 2 Diabetes"],"keywords":["Semaglutide; type 2 diabetes mellitus;Obesity;Glycemic Control; HbA1c; GLP-1 Receptor Agonist"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Rehman Medical Institute - RMI","slug":"rehman-medical-institute-rmi","class":"OTHER"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":95,"dates":{"start":"2022-07-04","primaryCompletion":"2023-03-30","completion":"2023-03-30","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["Pakistan"],"locations":[{"facility":"Rehman Medical Institute","status":null,"city":"Peshawar","state":"Khyber Pakhtunkhwa","country":"Pakistan","latitude":34.008,"longitude":71.57849}],"eligibility":{"criteria":"Inclusion Criteria:\n\nAdults aged 18 years or older. Established diagnosis of type 2 diabetes mellitus for at least 6 months. Glycated hemoglobin (HbA1c) between 7.5% and 10.0%. Body mass index (BMI) of at least 30 kg/m². Inadequate glycemic control despite ongoing standard diabetes therapy. Willing and able to provide written informed consent.\n\nExclusion Criteria:\n\nType 1 diabetes mellitus. Gestational diabetes mellitus. Severe renal impairment, defined as an estimated glomerular filtration rate of 30 mL/min/1.73 m² or less.\n\nPrevious or current treatment with any glucagon-like peptide-1 receptor agonist.\n\nHistory of chronic pancreatitis. History of pancreatic malignancy. Diabetic retinopathy requiring active treatment. Other significant ocular complications. Pregnancy or lactation. Known thyroid disorders. History or presence of thyroid neoplasms.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide (Ozempic®)","description":"participants received semaglutide by subcutaneous injection once weekly for 16 weeks. smaglutide was initiated at 0.25mg once weekly for the first 4 weeks, followed by 0.5mg once weekly for the subsequent 12 weeks"}],"primaryOutcomes":[{"measure":"Change in Glycated hemoglobin","description":"Absolute change in hemoglobin from baseline to end of 16 weeks once weekly semaglutide treatment","timeFrame":"baseline and 16 week"},{"measure":"Changes in Glycated Hemoglobin","description":"Absolute change in HBA1c from baseline to the end of 16 weeks of once weekly semaglutide treatment.","timeFrame":"Baseline and week 16"}],"secondaryOutcomes":[{"measure":"Changes in body weight","description":"Changes in body weight, measured in kgs, from baseline to week 16","timeFrame":"baseline to week 16"},{"measure":"Changes in BMI","description":"Changes in BMI, MEASURED IN KGS PER SQUARE METER, from baseline to week 16","timeFrame":"rom baseline to week 16"},{"measure":"Changes in fasting Blood Glucose","description":"Changes in Fasting blood glucose from baseline to week 16","timeFrame":"baseline to week 16"},{"measure":"Change in random blood glucose","description":"Change in random blood glucose from baseline to week 16","timeFrame":"Baseline to week 16"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07732218"},{"nctId":"NCT07732348","title":"Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist for Ovarian Stimulation in IVF/ICSI","officialTitle":"Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist in Controlled Ovarian Stimulation for In Vitro Fertilization: A Randomized Controlled Non-Inferiority Trial With a Concurrent Comparator Cohort Undergoing Progestin-Primed Ovarian Stimulation (PPOS)","summary":"This study compares two medications used to prevent a premature hormone surge (LH surge) during controlled ovarian stimulation for in vitro fertilization (IVF). The standard approach uses an injectable GnRH antagonist (ganirelix or cetrorelix), given as a daily injection under the skin. This study evaluates linzagolix, an oral GnRH antagonist already approved for uterine fibroids and endometriosis, used here for the first time in ovarian stimulation (off-label use).\n\nWomen undergoing IVF/ICSI at CENTRO AMBRA will be randomly assigned (1:1) to receive either oral linzagolix (200 mg/day) or the standard injectable antagonist. The study's hypothesis is that linzagolix is not inferior to the injectable antagonist in the number of mature (MII) eggs retrieved, within a pre-specified margin of 2.0 oocytes, while offering the advantage of oral rather than injectable administration.\n\nA separate, non-randomized group of women who are clinically indicated for a progestin-based stimulation protocol (PPOS) with a freeze-all strategy will be enrolled at the same time for descriptive comparison.\n\nSecondary objectives include how effectively each treatment suppresses the LH surge, whether a GnRH agonist can be used to safely trigger final egg maturation under linzagolix, the occurrence of ovarian hyperstimulation syndrome (OHSS) and other safety outcomes, the length of stimulation and amount of hormone medication needed, and embryology outcomes such as fertilization and blastocyst formation rates.\n\nThe study plans to enroll approximately 189 women in total.","detailedDescription":"Controlled ovarian stimulation (COS) for in vitro fertilization requires prevention of a premature LH surge. The established approaches are the injectable GnRH antagonist (ganirelix or cetrorelix), the current standard of care, and progestin-primed ovarian stimulation (PPOS), which suppresses the LH surge with an oral progestin but renders the endometrium non-receptive, requiring a mandatory freeze-all strategy. Oral, non-peptide GnRH antagonists (relugolix, elagolix, linzagolix) are approved for uterine fibroids and endometriosis but have not previously been used in ovarian stimulation cycles. This study addresses that gap and represents the first documented use of linzagolix in this indication.\n\nLinzagolix is an oral, non-peptide GnRH receptor antagonist with dose-dependent suppression of the pituitary-ovarian axis. At 200 mg/day it fully suppresses endogenous estradiol secretion; however, in COS the ovary is driven by exogenous FSH acting directly on the follicle, independent of the pituitary, so follicular growth and estradiol production are preserved while linzagolix acts specifically to prevent the endogenous LH surge. The study hypothesis is that this mechanism yields oocyte yield non-inferior to the injectable antagonist, with the added benefit of oral administration.\n\nThe feasibility of using a GnRH agonist as the final maturation trigger under an oral antagonist depends on residual receptor occupancy at the time of trigger. Linzagolix has a half-life of approximately 15-20 hours and reaches steady state in about 7 days, compared with relugolix (associated with reduced oocyte retrieval when combined with agonist trigger), which has a substantially longer half-life (approximately 37-42 hours) and reaches steady state in about 12 days. The faster clearance of linzagolix is expected to leave lower residual receptor occupancy at trigger, allowing an adequate LH/FSH flare from agonist trigger; preliminary center experience is consistent with this. Prospective verification of agonist-trigger feasibility under linzagolix is an explicit secondary objective, with particular relevance for OHSS prevention via agonist trigger combined with freeze-all in high responders.\n\nBecause a freeze-all strategy temporally and biologically decouples embryo transfer from the stimulation cycle, the only pathway by which the LH-suppression method, gonadotropin type, or trigger type could affect reproductive outcomes is oocyte and embryo competence, captured by the primary endpoint (MII count) and secondary embryology parameters. Reproductive outcomes are therefore collected as descriptive data but are not direct endpoints of the stimulation comparison.\n\nDesign: This is a single-center study at CENTRO AMBRA comprising two components with distinct inferential status. The comparison between linzagolix and the injectable GnRH antagonist is an open-label, randomized, controlled, non-inferiority trial with parallel groups and 1:1 allocation; only randomized patients are included in the two antagonist arms. A third, non-randomized PPOS group is concurrently enrolled by clinical indication (freeze-all candidates, e.g., for PGT-A) and serves as a comparative cohort. The randomization sequence is computer-generated with permuted blocks of variable size, prepared by staff not involved in enrollment, with allocation concealed via sequentially numbered sealed opaque envelopes or a centralized system and revealed only after eligibility confirmation and informed consent. Stratification is by ovarian-reserve responder category (normal/poor/high, defined by AMH and AFC); given the single-center sample size, Pocock-Simon minimization on responder category and age is an acceptable pre-specified alternative. The study is open-label given the oral versus subcutaneous routes of administration, but laboratory staff assessing oocyte and embryo outcomes are kept blinded to allocation. Eligible patients who are not randomized (refusal, contraindication, clinical or organizational reasons) are logged in a screening registry and reported in the CONSORT flow diagram with reason, without being included in the study. The PPOS cohort comparison is observational and subject to confounding by indication, given that the linzagolix arm is not restricted to patients with a freeze-all indication; it is analyzed with mandatory multivariable adjustment and sensitivity analyses restricted to comparable patients, and is interpreted as exploratory and hypothesis-generating. The unit of analysis is one cycle per patient (the first study cycle), to preserve independence of observations.\n\nSample size: The design is based on preliminary center data showing a within-group standard deviation of approximately 5.8 MII oocytes, with a strong correlation between MII count and ovarian reserve (AMH, AFC) allowing substantial variance reduction through ANCOVA. Assuming a conservative R² of 0.60 for the adjustment model, the expected residual standard deviation is approximately 3.7 oocytes. With a non-inferiority margin of 2.0 MII oocytes, one-sided alpha of 0.025, and 80% power, 53 analyzable patients per arm are required. Accounting for an expected 15% rate of cancellation/dropout, 63 patients per arm will be randomized (126 across the two antagonist arms), with the PPOS cohort sized at approximately 63 patients, for a total of approximately 189 patients. The margin of 2.0 MII oocytes was defined on clinical rather than statistical grounds, corresponding to a difference that would not alter clinical management, insemination strategy, transfer strategy, or expected cumulative prognosis. Sample size is fixed a priori; no interim efficacy or futility analyses or sample size re-estimation are planned.\n\nStatistical analysis: The primary analysis compares MII oocyte count between the linzagolix and injectable antagonist arms using ANCOVA, adjusted for ovarian reserve (AMH/AFC or responder category), age, and initial gonadotropin dose, with negative binomial regression as a pre-specified alternative in case of overdispersion. Non-inferiority is concluded if the lower bound of the two-sided 95% confidence interval for the adjusted mean difference exceeds -2.0 MII oocytes. Both intention-to-treat and per-protocol populations are analyzed, with non-inferiority requiring concordant results across both. Randomized patients whose cycle is cancelled before oocyte retrieval are included in the ITT analysis with an MII count of zero; sensitivity analyses excluding cancelled cycles are pre-specified. If non-inferiority is demonstrated, superiority testing on the same endpoint may proceed via a closed hierarchical procedure without alpha inflation. The comparison with the PPOS cohort uses mandatory multivariable adjustment (age, BMI, ovarian reserve, gonadotropin type/dose, PGT-A indication), with sensitivity analyses restricted to comparable patients and, where sample size allows, propensity scoring; results are reported as associations, not causal effects.","peptideSlugs":["cetrorelix","ganirelix"],"peptideNames":["Cetrorelix","Ganirelix"],"conditions":["Infertility, Female","Ovulation Induction"],"keywords":["Oral GnRH Antagonist","Linzagolix","Controlled Ovarian Stimulation","In Vitro Fertilization","ICSI","Progestin-Primed Ovarian Stimulation","Oocyte Maturation","OHSS Prevention"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Centro A.M.B.R.A. (Associazione Medici e Biologi per la Riproduzione Assistita)","slug":"centro-a-m-b-r-a-associazione-medici-e-biologi-per-la-riproduzione-assistita","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["EARLY_PHASE1"],"slugs":["early-phase-1"],"labels":["Early Phase 1"],"label":"Early Phase 1","highest":0.5},"studyType":"INTERVENTIONAL","enrollment":189,"dates":{"start":"2026-09","primaryCompletion":"2026-12","completion":"2026-12","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Female, aged 18 to 42 years\n* Indication for IVF/ICSI with controlled ovarian stimulation at CENTRO AMBRA\n* Population unselected for ovarian reserve (normal, poor, and high responders are eligible)\n* Written informed consent, including consent for off-label use of linzagolix and for data processing\n* For the two antagonist arms (Linzagolix and Injectable GnRH Antagonist): acceptance of randomization\n\nExclusion Criteria:\n\n* Known contraindications or hypersensitivity to the study drugs\n* Uterine pathology relevant to the study outcome (e.g., uterine malformations, significant submucosal fibroids)\n* Contraindications to pregnancy or to ovarian stimulation\n* Concurrent participation in another interfering interventional study","minimumAge":"18 Years","maximumAge":"42 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Linzagolix","description":"Linzagolix Type: Drug Arm: A Description: Linzagolix 200 mg administered orally once daily, started per center protocol (fixed stimulation day or upon appearance of the dominant follicle) and continued through the day of trigger. Investigational off-label use for suppression of the premature LH surge during controlled ovarian stimulation."},{"type":"DRUG","name":"Ganirelix ; Cetrorelix","description":"Ganirelix Type: Drug Arm: B Description: Ganirelix acetate 0.25 mg administered by daily subcutaneous injection, per fixed or flexible protocol according to center practice, to suppress the premature LH surge during controlled ovarian stimulation.\n\nCetrorelix Type: Drug Arm: B Description: Cetrorelix acetate 0.25 mg administered by daily subcutaneous injection, per fixed or flexible protocol according to center practice, to suppress the premature LH surge during controlled ovarian stimulation."},{"type":"DRUG","name":"Medroxyprogesterone Acetate ; Dienogest ; Micronized Progesterone","description":"Medroxyprogesterone Acetate Type: Drug Arm: C Description: Medroxyprogesterone acetate 10 mg/day administered orally from stimulation day 1-2 through the day of trigger, as part of a progestin-primed ovarian stimulation (PPOS) protocol with mandatory freeze-all strategy.\n\nDienogest Type: Drug Arm: C Description: Dienogest 2 mg/day administered orally from stimulation day 1-2 through the day of trigger, as part of a progestin-primed ovarian stimulation (PPOS) protocol with mandatory freeze-all strategy.\n\nMicronized Progesterone Type: Drug Arm: C Description: Micronized progesterone 100-200 mg/day administered orally from stimulation day 1-2 through the day of trigger, as part of a progestin-primed ovarian stimulation (PPOS) protocol with mandatory freeze-all strategy."}],"primaryOutcomes":[{"measure":"Number of Mature (MII) Oocytes Retrieved","description":null,"timeFrame":"At oocyte retrieval, approximately 36 hours after trigger (first study cycle)"}],"secondaryOutcomes":[{"measure":"Incidence of Premature LH Rise","description":null,"timeFrame":"From initiation of LH-suppressive treatment to the day of trigger (up to approximately 12 days)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07732348"},{"nctId":"NCT07732426","title":"Effects of Semaglutide on Brain Dopamine Responses to Food Cues in Adults With Obesity and Food Addiction Tendencies","officialTitle":"A Prospective Clinical Study to Investigate Dopamine Level Changes in the Brain at Food Cognition by GLP-1 Receptor Agonists","summary":"The goal of this clinical trial is to investigate how semaglutide affects the way the brain responds to food in adults with obesity and food addiction tendencies.\n\nThe main goals of this study are:\n\n* To see if semaglutide changes dopamine-related activity in the brain during the look, smell, and drink period.\n* To see if semaglutide changes dopamine-related brain signals during the post-ingestive period.\n* To see if semaglutide changes psychological survey results and cognitive task results.\n\nAdults with obesity and food addiction tendencies will join this study. Each participant will receive semaglutide treatment for 8 weeks. Each participant will have two brain scans using \\[11C\\]raclopride PET.\n\nDuring each PET scan, participants will:\n\n* View food images.\n* Receive chocolate milk through a tube while lying in the scanner.\n* Use a tablet during the scan to rate their hunger, desire for the chocolate milk drink, and liking of the drink.","detailedDescription":"1. Background and Rationale\n\n   GLP-1 receptor agonists, including semaglutide, are effective treatments for obesity. However, the brain mechanisms underlying their effects on appetite, food reward, and eating behavior remain incompletely understood. Food-related visual and olfactory cues may engage dopamine-mediated reward pathways during the pre-ingestive phase, and post-ingestive signals may further influence dopamine signaling after food intake.\n\n   This study will use \\[11C\\]raclopride positron emission tomography (PET) to assess dopamine-related binding measures in the human brain. The study will examine whether semaglutide changes dopamine-related brain responses during food cue and drink exposure and during the post-ingestive period.\n2. Study Protocol and Procedures\n\nThis is a prospective clinical trial using a 2-by-2 crossover design. Participants will receive once-weekly semaglutide treatment for 8 weeks and will undergo two \\[11C\\]raclopride PET scans. The scans will be performed under conditions with and without the effect of semaglutide, depending on group assignment.\n\nBefore each PET imaging session, participants will complete baseline assessments, including body measurements, psychological surveys, and computer-based cognitive tasks. \\[11C\\]raclopride will then be administered according to the PET protocol. Participants will undergo brain PET imaging while lying in the scanner.\n\nDuring the imaging session, participants will complete a standardized chocolate milk drink task. This task includes a baseline period, exposure to chocolate milk images, smelling the chocolate milk drink, and the post-ingestive stage using the chocolate milk drink delivered through a tube. During the scan, participants will use a tablet to rate hunger, desire for the chocolate milk drink, and liking of the drink at set time points.\n\nThe same PET task procedures will be used across study conditions. This will allow researchers to compare dopamine-related PET measures, psychological survey results, and cognitive task results between conditions with and without the effect of semaglutide.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Food Addiction Tendency","Obesity","Overweight"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Seoul National University Hospital","slug":"seoul-national-university-hospital","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":30,"dates":{"start":"2026-07-15","primaryCompletion":"2028-02-29","completion":"2028-06-30","firstPosted":"2026-07-28","resultsPosted":null,"lastUpdated":"2026-07-28"},"hasResults":false,"locationCount":1,"countries":["South Korea"],"locations":[{"facility":"Seoul National University Hospital","status":"RECRUITING","city":"Seoul","state":null,"country":"South Korea","latitude":37.566,"longitude":126.9784}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Participants aged between 19 and 50 years.\n* Eligible for treatment with semaglutide, defined as either:\n* Initial body mass index (BMI) of 30 kg/m2 or higher; or\n* Initial BMI of 27 kg/m2 to less than 30 kg/m2 with at least one weight-related comorbidity, such as dysglycemia, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.\n* Mild or greater food addiction tendency, defined as a Yale Food Addiction Scale (YFAS) score of 3 or higher.\n* Able to understand the study tasks and provide appropriate responses.\n\nExclusion Criteria:\n\n* Use of medications that may affect body weight or dopaminergic medications within the past 2 months.\n* Known hypersensitivity to semaglutide.\n* Pregnant, breastfeeding, or planning to become pregnant.\n* Severe renal impairment, hepatic impairment, heart failure, acute pancreatitis, or thyroid disease.\n* Any medical condition, disease, or medical history that, in the investigator's judgment, would make it difficult for the participant to complete the study or would interfere with interpretation of the study results.\n* Allergy to ingredients in chocolate milk, including milk or soy, or to ingredients that may be present through cross-contamination, including egg, buckwheat, peanut, wheat, peach, tomato, walnut, pork, or beef.\n* Participants with both no self-reported preference for chocolate milk and a chocolate milk preference score of less than 5 on a 10-point visual analog scale (VAS).","minimumAge":"19 Years","maximumAge":"50 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide","description":"Participants receive an 8-week subcutaneous semaglutide dose-escalation treatment using Wegovy: 0.25 mg once weekly for the first 4 weeks, followed by 0.5 mg once weekly for the next 4 weeks."}],"primaryOutcomes":[{"measure":"Change in Dopamine Binding Potential During the Look, Smell, and Drink Period","description":"Dopamine D2/D3 receptor binding potential is measured using \\[11C\\]raclopride PET during the food cue and drink period. The outcome is the within-participant difference in binding potential between the on-drug and off-drug/post-washout conditions.","timeFrame":"Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation."}],"secondaryOutcomes":[{"measure":"Change in Dopamine Binding Potential During the Post-Ingestive Period","description":"Dopamine D2/D3 receptor binding potential is measured using \\[11C\\]raclopride PET during the post-ingestive period after the drink. The outcome is the within-participant difference in binding potential between the on-drug and off-drug/post-washout conditions.","timeFrame":"Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation."},{"measure":"State Food Craving Score","description":"State food craving is assessed using the General Food Cravings Questionnaire-State (G-FCQ-S). Each of the 15 items is evaluated on a 0 to 100 scale, where higher scores indicate greater intensity of the felt state.","timeFrame":"Immediately before and after PET imaging. Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation."},{"measure":"Chocolate Milk Liking, Chocolate Milk Wanting, and Fullness Ratings (VAS-100)","description":"Liking and wanting for the chocolate milk stimulus, as well as general fullness, are assessed repeatedly during PET imaging using 0-to-100 visual analogue scale ratings. For liking and wanting, higher scores indicate greater liking of or desire for the chocolate milk stimulus. For fullness, higher scores indicate greater subjective fullness. Ratings are collected at 15 predefined time points during each PET scan.","timeFrame":"During each 92-minute PET scan, at 10, 20, 30, 40, 50, 51, 54, 57, 60, 65, 70, 75, 80, 85, and 90 minutes."},{"measure":"Food-Specific Attentional Bias","description":"Food-specific attentional bias is assessed using a computer-based dot-probe task with webcam-based eye tracking. Bias is calculated from reaction time differences between probes replacing food versus neutral images, and from gaze-based measures including dwell time toward food versus neutral images and first saccade direction. Higher values indicate greater attentional bias toward food stimuli.","timeFrame":"Before PET imaging. Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation."}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07732426"},{"nctId":"NCT02476786","title":"Endocrine Treatment Alone for Elderly Patients With Estrogen Receptor Positive Operable Breast Cancer and Low Recurrence Score","officialTitle":"Endocrine Treatment Alone as Primary Treatment for Elderly Patients With Estrogen Receptor Positive Operable Breast Cancer and Low Recurrence Score","summary":"Multiple neoadjuvant endocrine trials demonstrate that women with good prognosis tumors can be identified. These trials have also demonstrated that there are not adverse effects on overall outcome if women are treated with neoadjuvant endocrine therapy for several months prior to definitive treatment. A new standard of care needs to be defined for elderly women with good prognosis estrogen receptor (ER)+ tumors, since these women may benefit from endocrine therapy alone to treat their cancer without compromising local and distant control. The investigators hypothesize that endocrine therapy alone provides adequate local and systemic control of breast cancer in a subpopulation of women 70 or older with ER+ breast cancer and low Ki67 scores.","detailedDescription":null,"peptideSlugs":["goserelin"],"peptideNames":["Goserelin"],"conditions":["Breast Cancer","Cancer of Breast","Breast Neoplasms","Cancer of the Breast"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Washington University School of Medicine","slug":"washington-university-school-of-medicine","class":"OTHER"},"collaborators":[{"name":"Genomic Health®, Inc.","slug":"genomic-health-inc","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":50,"dates":{"start":"2017-01-17","primaryCompletion":"2027-01-31","completion":"2032-07-31","firstPosted":"2015-06-19","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Washington University School of Medicine","status":"RECRUITING","city":"St Louis","state":"Missouri","country":"United States","latitude":38.62727,"longitude":-90.19789}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Newly diagnosed histologically or cytologically confirmed operable invasive breast cancer defined as cT1 or T2, N0-1, and M0.\n* Disease must be ER+ and HER2-.\n* Ki67 score/proliferative index ≤ 30% or low to intermediate mitotic index\n* Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) by ultrasound or mammogram.\n* 70 years of age or older.\n* ECOG performance status ≤ 3\n* Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).\n\nExclusion Criteria:\n\n* Prior surgery for this cancer\n* A history of other malignancy ≤ 5 years previous which would preclude endocrine treatment of their cancer.\n* Currently receiving any other investigational agents.\n* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study.\n* Uncontrolled intercurrent illness as determined by their treating physician which would limit compliance with study requirements.\n* Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with endocrine therapies. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.","minimumAge":"70 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"BEHAVIORAL","name":"FACT-B","description":"The FACT-B (Version 4) is a 37-item measure that contains the four general subscales along with the Breast Cancer-Specific subscale that assesses symptoms/concerns of particular relevance to breast cancer (e.g., body image, arm swelling and tenderness)."},{"type":"DRUG","name":"Goserelin","description":null},{"type":"DRUG","name":"Anastrozole","description":null},{"type":"DRUG","name":"Exemestane","description":null},{"type":"DRUG","name":"Fulvestrant","description":null},{"type":"DRUG","name":"Tamoxifen","description":null},{"type":"OTHER","name":"Archived tissue collection","description":null}],"primaryOutcomes":[{"measure":"Response rate","description":"* Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \\[Eur J Ca 45:228-247, 2009\\].\n* In each RECIST response category Oncotype DX scores will be summarized with mean, standard deviation, minimum, 1st, 2nd (median) and 3rd quartiles, and maximum values. OncotypeDx scores range from 0 to 100, with scores \\<18 indicating low risk.","timeFrame":"6 months"}],"secondaryOutcomes":[{"measure":"Breast cancer-specific survival","description":null,"timeFrame":"6 months"},{"measure":"Breast cancer-specific survival","description":null,"timeFrame":"1 year"},{"measure":"Breast cancer-specific survival","description":null,"timeFrame":"2 years"},{"measure":"Rate of overall survival","description":null,"timeFrame":"5 years"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT02476786"},{"nctId":"NCT04523922","title":"Oxytocin to Enhance Integrated Treatment for AUD and PTSD","officialTitle":"Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD","summary":"The primary objective of the proposed Stage II study is to examine the efficacy of oxytocin (OT) as compared to placebo in reducing (1) alcohol use disorder (AUD) symptoms, and (2) post-traumatic stress disorder (PTSD) symptoms among Veterans receiving COPE therapy (Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure). To evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment.","detailedDescription":"Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co-occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self-administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes. In a randomized controlled pilot study, our group found that OT administration prior to weekly Prolonged Exposure (PE) therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) AUD symptoms, and (2) PTSD symptoms among Veterans (50% women) receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; and standardized, repeated dependent measures of clinical outcomes at multiple time points. In addition, to investigate neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre-and post-treatment .","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["PTSD","Alcohol Use Disorder"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Medical University of South Carolina","slug":"medical-university-of-south-carolina","class":"OTHER"},"collaborators":[{"name":"National Institute on Alcohol Abuse and Alcoholism (NIAAA)","slug":"national-institute-on-alcohol-abuse-and-alcoholism-niaaa","class":"NIH"}],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":175,"dates":{"start":"2021-03-29","primaryCompletion":"2026-04-13","completion":"2026-04-13","firstPosted":"2020-08-24","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Medical University of South Carolina","status":null,"city":"Charleston","state":"South Carolina","country":"United States","latitude":32.77632,"longitude":-79.93275}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Male or female; U.S. military Veteran, any race or ethnicity; aged 18-70 years.\n2. Able to provide written informed consent.\n3. Meet DSM-5 diagnostic criteria for current moderate to severe alcohol use disorder.\n4. Meet DSM-5 diagnostic criteria for current PTSD as assessed by the CAPS-5.\n5. Participants may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or anxiety disorders. Concurrent substance use disorders (e.g., marijuana) are acceptable provided alcohol is the participant's primary substance of choice.\n6. Participants taking psychotropic medications will be required to be maintained on a stable dose for at least 4 weeks before study initiation.\n\nExclusion Criteria:\n\n1. Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with current suicidal or homicidal ideation and intent. Those participants will be referred clinically for services.\n2. Participants on psychotropic medications which have been initiated during the past 4 weeks.\n3. Acute alcohol withdrawal as indicated by CIWA-Ar scores \\>8.\n4. Pregnancy or breastfeeding for women.\n5. For MRI scan component: history of seizures or severe head injury, implanted metal devices or other metal (e.g., shrapnel). These participants will be eligible to enroll in the clinical trial but will not be eligible to participate in the neuroimaging component of the study.\n6. Currently enrolled in behavioral treatment for AUD or PTSD.","minimumAge":"18 Years","maximumAge":"70 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"40 IU Intranasal Oxytocin","description":"40 IU Intranasal Oxytocin self administered 30 minutes prior to each COPE session."},{"type":"DRUG","name":"Placebo","description":"Placebo (intranasal saline spray) self administered 30 minutes prior to each COPE session."},{"type":"BEHAVIORAL","name":"Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure","description":"12 weekly sessions of COPE therapy for PTSD and AUD."}],"primaryOutcomes":[{"measure":"Change in alcohol use","description":"Change in percent days abstinent and heavy drinking days as measured by the TimeLine Follow-Back (TLFB).","timeFrame":"From baseline to week 12 and 3 and 6 month follow ups"},{"measure":"Change in PTSD symptom severity - clinician rated","description":"Change in clinician-rated PTSD symptom severity will be measured with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).","timeFrame":"From baseline to week 12 and 3 and 6 month follow ups"},{"measure":"Change in PTSD symptom severity - self report","description":"Change in self-reported PTSD symptom severity will be measured with the PTSD Checklist for DSM-5 (PCL-5).","timeFrame":"From baseline to week 12 and 3 and 6 month follow ups"}],"secondaryOutcomes":[],"publications":[{"pmid":"36646315","citation":"Back SE, Flanagan JC, Killeen T, Saraiya TC, Brown DG, Jarnecke AM, Rothbaum AO, Joseph J, Ana ES, de Arellano A, Shoemaker HL, Dixon RA, Nietert PJ, Brady KT. COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans. Contemp Clin Trials. 2023 Mar;126:107084. doi: 10.1016/j.cct.2023.107084. Epub 2023 Jan 13."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT04523922"},{"nctId":"NCT04949633","title":"Oxytocin vs Prostaglandins for Labor Induction of Women With an Unfavorable Cervix After 24h of Cervical Ripening","officialTitle":"Oxytocine Versus Prostaglandines Pour le déclenchement du Travail Des Femmes Dont le Col Est défavorable après 24 Heures de Maturation Cervicale : Essai Multicentrique randomisé de Non infériorité","summary":"Twenty-two percent of deliveries in France are induced. In cases where labor is induced and cervix is unfavorable, cervical ripening prior oxytocin administration is advised in order to reduce the risk of cesarean delivery. Cervical ripening agents, pharmacological (prostaglandins) or mechanical are administered during 24 hours. After 24 hours, most women will be either delivered or in labor but 25% of women will require further induction of labor. For 16% of women who undergo cervical ripening, whatever the cervical ripening method, the cervix remains unchanged after 24 hours. The management of these women is not consensual and depends on the maternity unit where women are cared for.\n\nThis study seeks to identify the most appropriate strategy for the management of women with an unfavorable cervix after 24 hours of cervical ripening, a strategy which would be associated with the lowest maternal and perinatal morbidity but also with the best maternal satisfaction. Because both strategies are practiced in France, the trial would compare: induction of labor with oxytocin and repeated cervical ripening. The aim is to show that repeating cervical ripening is an unnecessary procedure. And more specifically that oxytocin administration is not associated with a higher caesarean delivery rate and that it reduces the time to delivery in comparison with cervical ripening with prostaglandins.","detailedDescription":"Twenty-two percent of deliveries in France are induced. In cases where labor is induced and cervix is unfavorable, cervical ripening prior oxytocin administration is advised in order to reduce the risk of cesarean delivery. Cervical ripening agents, pharmacological (prostaglandins) or mechanical are administered during 24 hours. After 24 hours, most women will be either delivered or in labor but 25% of women will require further induction of labor. For 16% of women who undergo cervical ripening, whatever the cervical ripening method, the cervix remains unchanged after 24 hours. The management of these women is not consensual and depends on the maternity unit where women are cared for. In some units, women are admitted into labor ward for induction of labor with oxytocin. Elsewhere cervical ripening is repeated in order to obtain a favorable cervix and to reduce the risk of caesarean delivery.\n\nThis study seeks to identify the most appropriate strategy for the management of women with an unfavorable cervix after 24 hours of cervical ripening, a strategy which would be associated with the lowest maternal and perinatal morbidity but also with the best maternal satisfaction. Because both strategies are practiced in France, the trial would compare: induction of labor with oxytocin and repeated cervical ripening. The policy of induction of labor with oxytocin, being the simpler strategy, would be acceptable if it did not lead to a substantially proportion of women with caesarean deliveries compared with a second cervical ripening. This multicenter non inferiority randomized trial will recruit women with an unfavorable cervix (bishop score ≤ 6) after 24 hours of cervical ripening (pharmacological or mechanical) and randomize them to either induction of labor with oxytocin or to a second cervical ripening with prostaglandins. The aim is to show that repeating cervical ripening is an unnecessary procedure. And more specifically that oxytocin administration is not associated with a higher caesarean delivery rate and that it reduces the time to delivery in comparison with cervical ripening with prostaglandins.","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["Cervical Ripening","Unfavorable Cervix"],"keywords":["cervical ripening","oxytocin","prostaglandin","cesarean delivery"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"University Hospital, Tours","slug":"university-hospital-tours","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":1494,"dates":{"start":"2021-09-28","primaryCompletion":"2027-09","completion":"2027-11","firstPosted":"2021-07-02","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":14,"countries":["France"],"locations":[{"facility":"Gynaecology-obstetrics, University Hospital, Angers","status":"RECRUITING","city":"Angers","state":null,"country":"France","latitude":47.47156,"longitude":-0.55202},{"facility":"Gynaecology-obstetrics, University Hospital, Bordeaux","status":"TERMINATED","city":"Bordeaux","state":null,"country":"France","latitude":44.84124,"longitude":-0.58046},{"facility":"Gynaecology-obstetrics, University Hospital, Brest","status":"RECRUITING","city":"Brest","state":null,"country":"France","latitude":48.39029,"longitude":-4.48628},{"facility":"Gynaecology-obstetrics, University Hospital, Clermont-Ferrand","status":"TERMINATED","city":"Clermont-Ferrand","state":null,"country":"France","latitude":45.77969,"longitude":3.08682},{"facility":"Gynaecology-obstetrics, Hospital St Joseph, Marseille","status":"TERMINATED","city":"Marseille","state":null,"country":"France","latitude":43.29695,"longitude":5.38107},{"facility":"Gynaecology-obstetrics, University Hospital, Nancy","status":"RECRUITING","city":"Nancy","state":null,"country":"France","latitude":48.68439,"longitude":6.18496},{"facility":"Gynaecology-obstetrics, University Hospital, Nantes","status":"RECRUITING","city":"Nantes","state":null,"country":"France","latitude":47.21725,"longitude":-1.55336},{"facility":"Gynaecology-obstetrics, University Hospital, Orléans","status":"RECRUITING","city":"Orléans","state":null,"country":"France","latitude":47.90248,"longitude":1.90407},{"facility":"Gynaecology-obstetrics, Port Royal Maternity Hospital, Paris","status":"RECRUITING","city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Gynaecology-obstetrics, University Hospital, Poitiers","status":"TERMINATED","city":"Poitiers","state":null,"country":"France","latitude":46.58261,"longitude":0.34348},{"facility":"Gynaecology-obstetrics, Hospital, Pontoise","status":"NOT_YET_RECRUITING","city":"Pontoise","state":null,"country":"France","latitude":49.05,"longitude":2.1},{"facility":"Gynaecology-obstetrics, University Hospital, Saint Etienne","status":"RECRUITING","city":"Saint-Etienne","state":null,"country":"France","latitude":45.43389,"longitude":4.39},{"facility":"Gynaecology-obstetrics, University Hospital, Strasbourg","status":"NOT_YET_RECRUITING","city":"Strasbourg","state":null,"country":"France","latitude":48.58392,"longitude":7.74553},{"facility":"Gynaecology-obstetrics, University Hospital, Tours","status":"RECRUITING","city":"Tours","state":null,"country":"France","latitude":47.39484,"longitude":0.70398}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Pregnant woman\n* ≥ 18 years old\n* With a singleton cephalic pregnancy\n* ≥37+0 weeks of gestation\n* Gestational age estimated from the first trimester ultrasound (realized between 11+0 and 13+6 weeks of gestation)\n* With a medical indication of labor with a previous pharmacological or mechanical cervical ripening of 24 hours\n* Bishop score ≤ 6 at inclusion (unfavorable cervix)\n* French health insurance policy holder\n* Written informed consent\n\nExclusion Criteria:\n\n* Any measures of legal protection\n* Prior caesarean section or uterine scar\n* Contra-indications to a vaginal delivery\n* Foetus with suspected severe congenital abnormalities\n* Pathological foetal heart rate\n* Contra-indications to ANGUSTA® (oral misoprostol, cervical ripening agent)\n* Contra-indications to PROPESS® (vaginal slow releasing system of dinoprostone, cervical ripening agent)\n* Contra-indications to PROSTINE® (vaginal gel of dinoprostone, cervical ripening agent)\n* Contra-indications for using oxytocin\n* Woman in labor","minimumAge":"18 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Prostaglandins","description":"Second cervical ripening lasting a maximum of 24 hours"},{"type":"DRUG","name":"Oxytocin","description":"Induction of labor with oxytocin."}],"primaryOutcomes":[{"measure":"Cesarean delivery rate","description":"The main outcome is the rate of caesarean delivery, whatever the indication of the caesarean delivery","timeFrame":"Up to 2 days after intervention"}],"secondaryOutcomes":[{"measure":"Time from intervention to delivery in hours","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The proportion of women who delivered within 12 hours of the intervention","description":null,"timeFrame":"Up to 12 hours after intervention"},{"measure":"Maternal satisfaction, assessed with the self administered ACE Questionnaire for Assessing Childbirth Experience (QACE)","description":null,"timeFrame":"1 month"},{"measure":"The proportion of women who require induction with oxytocin (for women in the control group)","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The indications of caesarean in case of caesarean delivery","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The proportion of women with an instrumental delivery","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The indications for the use of instruments in case of instrumental delivery","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The proportion of women suspected of per-partum infection","description":null,"timeFrame":"Up to 2 days after intervention"},{"measure":"The proportion of women with post-partum haemorrhage","description":null,"timeFrame":"Up to 1 day after delivery"},{"measure":"The proportion of women with severe Post-partum haemorrhage","description":null,"timeFrame":"Up to 2 days after intervention"}],"publications":[{"pmid":"37068892","citation":"De Berti M, Le Gouge A, Monmousseau F, Gallot D, Sentilhes L, Winer N, Legendre G, Desbriere R, Girault A, Pozzi J, Gachon B, Barjat T, Perrotin F, Brunet-Houdard S, Diguisto C; Groupe de Recherche en Gynecologie Obstetrique. Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial. BMJ Open. 2023 Apr 17;13(4):e058282. doi: 10.1136/bmjopen-2021-058282."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT04949633"},{"nctId":"NCT05071898","title":"Pharmacogenetics of Response to GLP1R Agonists","officialTitle":"Pharmacogenetics of Response to GLP1R Agonists","summary":"Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. Lancaster County, PA. Pharmacodynamic responses to GLP1R agonist will be assessed by conducting frequently sampled intravenous glucose tolerance tests (FSIGT) both before and after semaglutide for six weeks. The proposal proposes two specific aims:\n\n1. Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).\n2. Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).\n\nGenotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. In addition, the analysis will leverage a global imputation panel generated from 1,025 Amish individuals.","detailedDescription":"Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. In order to assess pharmacodynamic responses, research participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT). The first FSIGT will be conducted at baseline prior to administration of drug. The second FSIGT will be conducted after six weeks of treatment with semaglutide (0.25 mg/wk X 4 wks; 0.5 mg/sk X 2 wks). The proposal proposes two specific aims:\n\n* Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug).\n* Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug).\n\nAfter being determined to be eligible and after having given informed consent, participants will undergo two frequently samples intravenous glucose tolerance tests conducted at two clinic visits as described below:\n\nVisit #1 - Research participants will be transported to the Amish Research clinic in the fasting state (minimum of 8 hour, maximum of 24 hour fast) where height, weight, waist and hip measurements, and vital signs will be measured. Women of child-bearing potential will undergo a urine pregnancy test. An FSIVGTT will be conducted as follows: IV (intravenous) access will be established in both arms of the research participant, one for glucose infusion and the other for frequent blood sampling. NSS (normal saline solution) will be used to maintain patency of IV. Intravenous glucose (0.3 g/kg) will be infused over 2 min at time=0, and 31 blood samples will be obtained between -15 and +180 minutes. Approximately 180 ml (36 tsp.) of blood will be drawn. Upon completion of the FSIVGTT, the participant will be instructed in the self-administration of subcutaneous (s.c.) injection of semaglutide. The first dose of semaglutide .25mg will be administered at this time. The participant will be provided with a post-fasting meal.\n\nHome self-administration of weekly semaglutide: The participant will self-administer s.c. semaglutide weekly for 5 weeks (.25 mg for weeks 2,3,4 and .5 mg for weeks 5,6) A research nurse may observe the participant self-administering the first home dose and will make additional home visits as needed to ensure successful self-injection. The participant will use the study provided scale to obtain and record daily weights in the morning before breakfast throughout the medication weeks.\n\nVisit #2 - This visit will be scheduled within 1 week of the final (6th) dose of semaglutide +/- 5 days. The FSIVGTT will be conducted exactly as during the previous clinic visit.\n\nGenotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. The project will leverage a global imputation panel generated from whole genome sequence data on \\~ 100K subjects including 1,025 Amish individuals obtained through the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Obesity","Diabetes Type 2"],"keywords":["GLP-1 receptor agonist","Insulin secretion","Insulin sensitivity","Pharmacogenomics","Semaglutide"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"University of Maryland, Baltimore","slug":"university-of-maryland-baltimore","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":600,"dates":{"start":"2022-04-11","primaryCompletion":"2027-04-30","completion":"2028-04","firstPosted":"2021-10-08","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Amish Research Clinic","status":"RECRUITING","city":"Lancaster","state":"Pennsylvania","country":"United States","latitude":40.03788,"longitude":-76.30551}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* BMI greater than or equal to 27 kg/m2\n* Of Amish Descent\n\nExclusion Criteria:\n\n* Woman of childbearing age who is sexually active\n* History of diabetes (HbA1c \\> 6.5% or random glucose \\>200 mg/dL)\n* Known allergy to semaglutide\n* Medical issues, which in the judgment of the research physician or PIs might increase the risk associated with participation in the study\n* eGFR \\< 60 mL/min/1.73 sq. m.\n* Hematocrit \\< 35%\n* TSH \\< 0.4 o4 \\> 5.5\n* AST or ALT in excess of 2X the upper limit of normal\n* Unable to discontinue a drug, vitamin, or nutritional supplement, which in the judgment of the research physician or PIs might alter the response to semaglutide\n* Personal or family history of medullary carcinoma of the thyroid or multiple endocrine neoplasia, type 2","minimumAge":"18 Years","maximumAge":"89 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Semaglutide Pen Injector [Ozempic]","description":"Participants will receive subcutaneously injected semaglutide (0.25 mg/wk) for 4 weeks followed by semaglutide (0.5 mg/wk) for an additional two weeks."}],"primaryOutcomes":[{"measure":"First phase insulin secretion","description":"Area under the curve for plasma insulin levels measured at times between 0-10 min after administration of intravenous glucose (0.3 g/kg)","timeFrame":"Measured both at baseline and after completing 6 weeks of semaglutide therapy"},{"measure":"Second phase insulin secretion","description":"Area under the curve for plasma insulin levels measured at times between 10-50 min after administration of intravenous glucose (0.3 g/kg)","timeFrame":"Measured both at baseline and after completing 6 weeks of semaglutide therapy"},{"measure":"Rate of glucose disappearance","description":"Slope of the plot of log(glucose concentration) as a function of time. This will be calculated based on a linear regression using data points between 25-50 minutes after administration of intravenous glucose (0.3 g/kg)","timeFrame":"Measured both at baseline and after completing 6 weeks of semaglutide therapy"}],"secondaryOutcomes":[{"measure":"Weight loss","description":"This will be measured as the baseline weight in kg minus the weight after completing 6 weeks of semaglutide therapy.","timeFrame":"Assessed after completing 6 weeks of semaglutide therapy"}],"publications":[{"pmid":"37264484","citation":"Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05071898"},{"nctId":"NCT05173714","title":"Sit Less, Interact and Move More (SLIMM) 2 Study","officialTitle":"Sit Less, Interact and Move More (SLIMM) 2 Study","summary":"* Prolonged sitting (sedentary behavior) is a risk factor for decreased kidney function, obesity, diabetes and mortality. Prolonged sitting is associated with decreased kidney function and increased risk of diabetes, heart disease and death.\n* In a previous pilot study funded by NIH, it was shown that a Sit Less, Interact and Move More (SLIMM) intervention targeting sedentary behavior in people with kidney disease was able to decrease prolonged sitting but that effect was not sustained.\n* Therefore, the researchers are currently conducting a follow-up study named Sit Less, Interact and Move More (SLIMM) 2.\n* This NIH funded study is conducted at the University of Utah and Stanford University.\n* The purpose of this study is to see if guided resistance training (to improve muscle strength) and semaglutide (FDA approved diabetes and weight loss medication that might also improve physical function) can boost adherence to the SLIMM Intervention and reduce sedentary behavior.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Chronic Kidney Diseases","Obesity"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Srinvasan Beddhu","slug":"srinvasan-beddhu","class":"OTHER"},"collaborators":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","slug":"national-institute-of-diabetes-and-digestive-and-kidney-diseases-niddk","class":"NIH"},{"name":"Stanford University","slug":"stanford-university","class":"OTHER"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":156,"dates":{"start":"2021-12-01","primaryCompletion":"2026-12-31","completion":"2027-03-31","firstPosted":"2021-12-30","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"Stanford University","status":"RECRUITING","city":"Stanford","state":"California","country":"United States","latitude":37.42411,"longitude":-122.16608},{"facility":"University of Utah","status":"RECRUITING","city":"Salt Lake City","state":"Utah","country":"United States","latitude":40.76078,"longitude":-111.89105}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Glomerular Filtration Rate (eGFR) 20 to \\<60 mL/min/1.73m\\^2\n* Able to perform resistance training\n* Access to compatible \"smartphone\" or device (i.e., Android, Kindle or Apple with internet connectivity or mobile network), desktop or laptop\n\nExclusion Criteria:\n\n* Type 1 Diabetes\n* History of gastroparesis or paralytic ileus\n* At baseline, if sedentary time is 25 min/hr or less, measured by accelerometer\n* Potential contraindications to semaglutide such as a history of pancreatitis, and a family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma.\n* Previous bariatric surgery\n* Medical condition likely to limit survival to less than 1 year\n* Anticipated start of dialysis or kidney transplantation within 6 months\n* Any factors judged by the investigator or study team to likely limit adherence to interventions\n* Vulnerable populations- pregnant or incarcerated\n* Enrolled in interventional trials using drugs or devices\n* Not able to undergo informed consent\n* Recent hospitalizations or major interventional procedures done within the past 60 days\n* Known or suspected hypersensitivity to tegaderm\n* Use of any GLP-1 receptor agonist within 30 days prior to screening\n* Presently classified as being in New York Heart Association (NYHA) Class IV Heart Failure\n* Daytime use of supplemental oxygen (i.e., prescribed a stationary or portable oxygen system)\n* Presence of metastatic cancer\n* Current use of mobility aid(s)\n* Living in the same household of a participant already enrolled in the study","minimumAge":"20 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"BEHAVIORAL","name":"SLIMM","description":"Increase in light walking activity, replacing 1 hour/day of sedentary duration with casual walking duration. Increase in sedentary breaks, from sitting/lying position to standing position, at least once every hour as independent of the total time spent on sedentary activities."},{"type":"BEHAVIORAL","name":"Standard Resistance Training","description":"Participants will be provided a standard resistance training regimen to follow during the course of the study. Participants will not receive individualized instruction, guidance or modification to the resistance training regimen."},{"type":"BEHAVIORAL","name":"Guided Resistance Training","description":"Supervised resistance training sessions are individualized for a low-resistance, high-repetition regimen of lower body major muscle groups with established guidelines. Instructions and resistance training bands will be provided for home use. Study participants will record compliance to the resistance training regimen for further guidance and potential modification."},{"type":"DRUG","name":"Placebo","description":"Oral placebo tablets (matching the experimental semaglutide) will be administered from the first through ninth months of the drug intervention period."},{"type":"DRUG","name":"Semaglutide","description":"Oral semaglutide 3 mg/day will be administered for the first month of study drug intervention period, if tolerated, the dose will increase to 7 mg/day for the second month and to a maximum dose of 14 mg/day from the third through ninth months of the drug intervention period."}],"primaryOutcomes":[{"measure":"Average Change in Sedentary Duration at Months 8, 10 and 12 from Randomization","description":"The primary analysis will provide estimates and confidence intervals for the three arms comparisons of changes in sedentary duration from randomization (at 3 months) to the average of changes at months 8, 10 and 12 between the randomized groups that constitute the co-primary comparisons under the study design","timeFrame":"Randomization to 12 Months"}],"secondaryOutcomes":[{"measure":"Average Change in Steps per Day at Months 8, 10 and 12 from Randomization","description":"The analysis will provide estimates and confidence intervals for the three arms comparisons of changes in steps per day from randomization (at 3 months) to the average of changes at months 8, 10 and 12 between the randomized groups.","timeFrame":"Randomization to 12 Months"},{"measure":"Average Change in Stepping Duration at Months 8, 10 and 12 from Randomization","description":"The analysis will provide estimates and confidence intervals for the three arms comparisons of changes in stepping duration from randomization (at 3 months) to the average of changes at months 8, 10 and 12 between the randomized groups.","timeFrame":"Randomization to 12 Months"},{"measure":"Average Change in Six-Minute Walk at Months 6 and 12 from Randomization","description":"Changes in six minute walk distance from randomization (at 3 months) to the average of changes at months 6 and 12","timeFrame":"Randomization to 12 Months"},{"measure":"Average Change in Body Fat % at Months 6 and 12 from Randomization","description":"Changes in average body fat percentage as measured by bioimpedance analysis from randomization (at 3 months) to the average of changes at months 6 and 12","timeFrame":"Randomization to 12 Months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05173714"},{"nctId":"NCT06015893","title":"Semaglutide Therapy for Alcohol Reduction (STAR)","officialTitle":"Semaglutide Therapy for Alcohol Reduction (STAR): A Proof-of-Concept Phase II Clinical Trial","summary":"Background:\n\nAlcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed.\n\nObjective:\n\nTo test if a medication named Semaglutide may reduce alcohol drinking in people with AUD.\n\nWho can participate?\n\nAll Adults aged 18 or older with AUD might be eligible to participate in the study.\n\nWhat will happen during the study?\n\nParticipants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit.\n\nParticipants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine.\n\nThe study medication is given as a shot under the skin each week.\n\nParticipants will undergo different tests throughout the study:\n\nThey will give blood, urine, and saliva samples.\n\nThey will engage in self-paced behavioral therapy on a computer.\n\nThey will answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc.\n\nThey will taste several sweet liquids and tell their preferences.\n\nThey will sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol.\n\nThey will wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet.\n\nThey will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.They will perform tasks on a computer screen.\n\nParticipants will have a follow-up visit about 7 weeks after their last shot.","detailedDescription":"Study Description:\n\nThis study will test the safety/tolerability and early efficacy of subcutaneous (s.c.) semaglutide at the dose of 2.4 mg/week or maximum tolerated dose (MTD) as a potential new treatment for alcohol use disorder (AUD).\n\nObjectives:\n\nWe propose to test early efficacy and safety/tolerability of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, as a novel pharmacotherapy to reduce alcohol use and related measures. This will be a Phase 2a, pilot, proof-of-concept, outpatient study combined with experimental medicine human laboratory procedures.\n\nEndpoints:\n\nThe primary aims will be to determine whether semaglutide reduces alcohol drinking from baseline to endpoint, as measured by total number of standard alcohol-containing drinks consumed per week (drinks per week, DPW). Semaglutide is safe and tolerable in individuals with AUD, as measured by the frequency/severity of adverse events and the proportion of participants who reach maximum dose, and B) semaglutide reduces alcohol drinking from baseline to endpoint, as measured by total number of standard alcohol-containing drinks consumed per week (drinks per week, DPW).\n\nThe following secondary aims will also be examined:\n\n* Whether semaglutide is safe and tolerable, as assessed by the number and severity of adverse events and the proportion of participants who reach the target dose.\n* Whether semaglutide reduces other self-reported alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, World Health Organization (WHO) drinking levels)\n* Whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use\n* Whether semaglutide reduces alcohol and/or food cue-elicited craving assessed in a bar-like laboratory\n* Whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Addiction","Alcohol Use Disorder"],"keywords":["Alcohol","Pharmacotherapy","GLP-1","Semaglutide"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute on Drug Abuse (NIDA)","slug":"national-institute-on-drug-abuse-nida","class":"NIH"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":63,"dates":{"start":"2023-10-17","primaryCompletion":"2027-03-31","completion":"2027-03-31","firstPosted":"2023-08-29","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institute on Drug Abuse","status":null,"city":"Baltimore","state":"Maryland","country":"United States","latitude":39.29038,"longitude":-76.61219}],"eligibility":{"criteria":"* INCLUSION CRITERIA:\n\nThis study will enroll adult individuals with a current diagnosis of AUD. Participants will be recruited without any preference to sex, race, religion, or other social variables, but sociodemographic data will be collected for sample characterization and potential use in the analyses. Since self-reported psychological measures that have been validated in English constitute major part of the study assessments, participants need to be able to speak, read, write, and understand English to be in the study.\n\nThe information needed to assess eligibility will be collected under an IRB-approved NIDA IRP\n\nscreening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to assess\n\npotential research participants' eligibility for entering clinical protocols. Additional details can be found in the NIDA screening protocol documents. Furthermore, NIH medical records (from other NIH clinical protocols) and outside medical records may also be used, if available, to determine whether participants fulfill the eligibility criteria.\n\nTo be eligible for this study, an individual must meet all of the following criteria:\n\n* At least 18 years old\n* Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))\n* Self-reported drinking, according to alcohol Timeline Follow-Back (TLFB), of \\> 7 drinks per week for females or \\> 14 drinks per week for males during the 28-day period prior to screening plus at least four days with \\> 3 drinks for females or \\> 4 drinks for males during the 28-day period prior to screening\n* Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score \\< 10\n* Able to speak, read, write, and understand English as demonstrated by ability to understand and sign the NIDA screening protocol consent\n* Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or corrected-to-normal (e.g., with the use of a hearing aid) hearing\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from enrolling in this study:\n\n* BMI \\< 23 kg/m\\^2 or BMI \\>= 50 kg/m\\^2\n* Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)\n* Most recent blood tests: creatinine \\>= 2 mg/dL, eGFR \\<45 mL/min/1.73 m\\^2, triglycerides \\> 500 mg/dl, ALP \\> 4x the upper limit of normal, clinically abnormal lipase levels per study clinician\n* Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) \\>= 6.5 %\n* Current (within the past 30 days) use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors\n* Current or prior use of semaglutide or tirzepatide\n* Current (within the past 30 days) use of weight-lowering medications\n* Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or intramuscular naltrexone, acamprosate, disulfiram)\n* Current (within the past 30 days) use of medications with known interaction with semaglutide\n* Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)\n* Known ongoing history of alcohol ketoacidosis, gastroparesis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis\n* Known history of gastric bypass surgery\n* Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue\n* Known history of suicidal attempts (within the past 24 months) or active suicidal ideation\n* Known history of clinically significant vestibular disorders or motion sickness\n* Known history of clinically significant noise-induced hearing loss or tinnitus\n* Contraindication(s) for brain fMRI\n* Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)\n* Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable during the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the past twelve months prior to screening.\n* Female who is pregnant, breast-feeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method\n* Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant","minimumAge":"18 Years","maximumAge":"110 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"BEHAVIORAL","name":"Take Control","description":"A computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials."},{"type":"DRUG","name":"Semaglutide","description":"Weekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD)."}],"primaryOutcomes":[{"measure":"Determine whether semaglutide, compared to placebo, reduces alcohol drinking.","description":"Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.","timeFrame":"Difference in number of standard alcohol-containing drinks consumed / week (Drinks Per Week, DPW) from baseline to end of the study."}],"secondaryOutcomes":[{"measure":"Determine whether semaglutide reduces brain activity in resting-state and/or task-based fMRI scans.","description":"Differences in fMRI outcomes will demonstrate whether the drug changes brain activity at rest and/or in response to tasks.","timeFrame":"Difference in relevant fMRI measures between the two groups."},{"measure":"Determine whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory.","description":"Differences in food choices selected will demonstrate whether the drug changes food-seeking behaviors in a population with AUD.","timeFrame":"Difference in food selection in the virtual buffet between the two groups."},{"measure":"Determine whether semaglutide reduces alcohol/food cue-elicited craving assessed in a bar-like laboratory.","description":"Differences in craving scores will demonstrate whether the drug changes cue-reactivity in a population with AUD.","timeFrame":"Difference in alcohol/food craving scores post exposure between the two groups."},{"measure":"Determine whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use.","description":"Recording the difference of blood PEth levels between baseline and end of the study will provide an objective biomarker of change in alcohol use throughout the study, potentially due to the use of semaglutide.","timeFrame":"Difference in blood PEth levels from baseline to end of the study."},{"measure":"Determine whether semaglutide, compared to placebo, reduces other self-reported alcohol-related outcomes.","description":"Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.","timeFrame":"Difference in other alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, WHO drinking levels) from baseline to end of the study."},{"measure":"Determine the safety and tolerability of semaglutide in individuals with AUD.","description":"High numbers of serious adverse events negatively reflect a drug s safety and tolerability in a specific patient population.","timeFrame":"Number and severity of adverse events; number of people who reach the target dose."}],"publications":[{"pmid":"26308095","citation":"Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015 Sep 24;58(18):7370-80. doi: 10.1021/acs.jmedchem.5b00726. Epub 2015 Sep 11."},{"pmid":"28323117","citation":"Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjornsdottir I, Pedersen PJ, Rowe E, Derving Karsbol J, Pedersen ML. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41. doi: 10.1016/j.ejps.2017.03.020. Epub 2017 Mar 16."},{"pmid":"21950636","citation":"Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol. 2012 May;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x."},{"pmid":"26080318","citation":"Suchankova P, Yan J, Schwandt ML, Stangl BL, Caparelli EC, Momenan R, Jerlhag E, Engel JA, Hodgkinson CA, Egli M, Lopez MF, Becker HC, Goldman D, Heilig M, Ramchandani VA, Leggio L. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence. Transl Psychiatry. 2015 Jun 16;5(6):e583. doi: 10.1038/tp.2015.68."},{"pmid":"33424537","citation":"Marty VN, Farokhnia M, Munier JJ, Mulpuri Y, Leggio L, Spigelman I. Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats. Front Neurosci. 2020 Dec 23;14:599646. doi: 10.3389/fnins.2020.599646. eCollection 2020."},{"pmid":"37192005","citation":"Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, Marchette RC, Koob GF, Roberto M, Vendruscolo LF, Leggio L. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023 Jun 22;8(12):e170671. doi: 10.1172/jci.insight.170671."},{"pmid":"36001436","citation":"Farokhnia M, Browning BD, Crozier ME, Sun H, Akhlaghi F, Leggio L. The glucagon-like peptide-1 system is modulated by acute and chronic alcohol exposure: Findings from human laboratory experiments and a post-mortem brain study. Addict Biol. 2022 Sep;27(5):e13211. doi: 10.1111/adb.13211."},{"pmid":"35906358","citation":"Farokhnia M, Fede SJ, Grodin EN, Browning BD, Crozier ME, Schwandt ML, Hodgkinson CA, Momenan R, Leggio L. Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use. Sci Rep. 2022 Jul 29;12(1):13027. doi: 10.1038/s41598-022-17190-3."},{"pmid":"34532853","citation":"Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb;179(4):625-641. doi: 10.1111/bph.15677."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06015893"},{"nctId":"NCT06072963","title":"COMMETS- Combination MCI Metabolic Syndrome","officialTitle":"Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study","summary":"The investigators propose a proof of concept RCT (randomized clinical trial), testing the efficacy of intranasal insulin (INI) with semaglutide, a combination therapy with strong biological plausibility to benefit impaired cognition through vascular mechanisms, in older adults with MetS (metabolic syndrome) and MCI (Mild Cognitive Impairment), who are enriched for cerebrovascular disease and at high dementia risk. The study will focus on cognitive and biological outcomes, allowing identification of relevant mechanisms.","detailedDescription":"The Specific Aims of the study are:\n\nAim 1. To examine the ease and precision of use of the intranasal device and once daily semaglutide pill.\n\nAim 2. To examine the adherence to the two types of treatment.\n\nAim 3. To examine the safety profile of the combination of intranasal insulin with semaglutide. The safety profile of each has been published broadly, but the safety of their combination has not been examined.\n\nAim 4. Although the primary goal of the pilot study is proof of concept essential to design a large combination therapy RCT, The investigators will compare the combination of intranasal insulin and semaglutide with the other three groups on a) cognition, b) cerebral blood flow (via ASL MRI), c) glucose uptake (via FDG PET), ADRD(Alzheimer's disease and related disorders)-related blood biomarkers (Aβ42/Aβ40 ratio, pTau181 and 231, NfL and GFAP), and expression of insulin signaling genes from brain derived exosomes.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Alzheimer Disease","Mild Cognitive Impairment","Metabolic Syndrome"],"keywords":["Alzheimer disease","Mild Cognitive Impairment","Metabolic syndrome","Dementia","Semaglutide","Intranasal insulin"],"conditionGroups":[{"slug":"brain-health","label":"Brain health"}],"sponsor":{"name":"Rutgers, The State University of New Jersey","slug":"rutgers-the-state-university-of-new-jersey","class":"OTHER"},"collaborators":[{"name":"Alzheimer's Association","slug":"alzheimer-s-association","class":"OTHER"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":80,"dates":{"start":"2024-01-30","primaryCompletion":"2027-12-01","completion":"2028-12-01","firstPosted":"2023-10-10","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["Israel"],"locations":[{"facility":"Joseph Sagol Neuroscience center, Sheba Medical Center","status":"RECRUITING","city":"Ramat Gan","state":null,"country":"Israel","latitude":32.08227,"longitude":34.81065}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Diagnosis of MCI (based on a MOCA \\<27 and a clinical dementia rating scale \\[CDR\\] score of 0.5 representing questionable dementia).\n* Diagnosis of MetS -requiring a) abdominal obesity (waist circumference \\>102cm for men and \\>88cm for women), and b) glucose intolerance (fasting glucose\\>110 mg/dL) and at least one of the following-c) dyslipidemia (high triglycerides \\[\\>150 mg/dL\\] and low HDL \\[\\<40mg/dL for men and \\<50 mg/dL for women\\]), or d) elevated blood pressure (\\>130/\\>85 mmHg).\n* Fluent in Hebrew\n* The study requires an active study partner\n\nExclusion Criteria:\n\n* Diabetes (of any type)\n* Taking medications that may affect glucose metabolism (including a GLP-1RA).\n* Diagnosis of dementia and its subtypes, conditions that may directly affect cognition,\n* short life expectancy or a medical condition that precludes consistent participation in the study,\n* contraindications to either insulin or Semaglutide.\n* Medications that may affect glucose metabolism such as corticosteroids.","minimumAge":"60 Years","maximumAge":"90 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide","description":"The medication is available in 3, 7, and 14-mg tablets for oral use. Participants will be instructed to start with an initiating dose of 3 mg once daily. If they do not experience adverse events (nausea, vomiting, and abdominal pain) then the dose will be titrated to 7 mg once daily after 30 days. Again, if the participant does not experience adverse events, the dose will be further titrated after 30 days to 14 mg once daily. This does will continue until the end of the study, at 12 months."},{"type":"DRUG","name":"Intranasal insulin","description":"The study will use the ViaNase; Kurve Technology intranasal device to administer insulin intra-nasally. This device has been used in other studies of persons with AD and has shown insulin penetration into the brain via CSF studies. Through sniffing, the medication crosses the blood-brain barrier (BBB) at the top of the nasal cavity. Participants will be instructed to press a switch that will turn on the device, engaging a pump that releases a nebulized stream of insulin through a nose piece into a nostril for 20 seconds (the device includes an electronic timer), after which the device switches off. The process is then repeated in the other nostril. The investigators decided on administration of 20IU of INI twice per day as the literature suggests this as the optimal dosage."},{"type":"OTHER","name":"Semaglutide placebo","description":"Rybelsus semaglutide - this medicine will simulate taking the pill Rybelsus /semaglutide once a day. A pill identical to the medicine pill will be given."},{"type":"OTHER","name":"Intranasal insulin placebo","description":"The placebo used in this study is saline. The investigators will administer saline, with exactly the same methods as the INI insulin (twice per day, 20 seconds each sniff, in each nostril."}],"primaryOutcomes":[{"measure":"Cognitive change - The effect of the combination of Semaglutide and intranasal insulin on cognitive functioning.","description":"The cognitive outcome is a balanced composite sum of z-scores of four executive function tests (Trails B, Digit-Symbol, and Category Fluency (animals, fruits and vegetables), four episodic memory tests (immediate and delayed recall of the word list from the ADAS-Cog, and immediate and delayed recall of Logical Memory Story I from the Wechsler Memory Test). Z-scores are reversed if necessary so that a positive value refers to good cognition. Cognitive functioning will be measured at baseline, 6 months, and 12 months follow-ups.","timeFrame":"12 months"},{"measure":"Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on cerebral blood flow (CBF).","description":"Change in CBF will be measured using Arterial Spin Labeling (ASL) brain magnetic resonance imaging (MRI) scans. The unit of cerebral blood flow from ASL is ml/100g/min, which means the amount of blood flow into 100g of tissue in one minute. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in blood flow between the time points.","timeFrame":"6 months"},{"measure":"Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on brain glucose intake.","description":"Brain Glucose intake will be measured by \\[F18\\]FDG-PET: Voxel-wise standardized uptake value ratio (SUVR) images will be created in native MRI space with the pons as reference region. \\[F18\\]FDG values will be extracted from ADRD-vulnerable regions of interest (dorsolateral prefrontal cortex, medial and lateral temporal lobe, and medial and lateral parietal cortex). Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in glucose intake between the time points.","timeFrame":"6 months"}],"secondaryOutcomes":[{"measure":"Change in specific cognitive domains - The effect of the combination of Semaglutide and intranasal insulin on executive functions and episodic memory.","description":"Cognitive outcomes will be the domain-specific composites, for executive functions and episodic memory, by using four executive function tests (Trails B, Digit-Symbol, and Category Fluency \\[animals, fruits and vegetables), and four episodic memory tests (immediate and delayed recall of the word list from the ADAS-Cog, and immediate and delayed recall of Logical Memory Story I from the Wechsler Memory Test). Cognitive outcomes will be measured at baseline, 6 months, and 12 months follow-ups","timeFrame":"12 months"},{"measure":"Neuroimaging outcomes- The effect of the combination of Semaglutide and intranasal insulin on microstructural alterations indicative of tissue injury.","description":"Changes in White matter hyperintensity (WMH) volume: Total WMH volume of presumed ischemic origin will be quantified from 3D T2-FLAIR brain MRI using the Lesion Segmentation Tool. T1-weighted volumetric scans will be used to derive intracranial volume. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in WMH volume between the time points.","timeFrame":"6 months"},{"measure":"Neuroimaging outcomes- The effect of the combination of Semaglutide and intranasal insulin on gray matter and hippocampal volume.","description":"Changes in gray matter (GM) and hippocampal volumes: neurodegeneration will be measured using T1-weighted scans brain MRI scans. Regional cortical GM and hippocampal volumes will be extracted using FreeSurfer 7.1.1. and FSL. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in GM and hippocampal volumes between the time points.","timeFrame":"6 months"},{"measure":"Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on functional performance.","description":"Change in functional performance will be measured by the Clinical Dementia Rating (CDR) Scale Sum of Boxes (SB). The CDR-SB summarizes cognitive impairment in 6 domains (memory, orientation, judgment/problem-solving, community affairs, home/hobbies, and personal care) based on subject and informant interviews. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). A maximal CDR-SB score is -18. CDR will be measured at baseline, 6 months, and 12 months follow-ups.","timeFrame":"12 months"},{"measure":"Functional outcome - The effect of the combination of Semaglutide with intranasal inulin on change in functional performance as measured by IADL (instrumental activities of daily living) questionnaires.","description":"Functional Activities will be based on subject and informant interviews. Both ADLs (activities of daily living) and IADLs (instrumental ADLs) refer to key life tasks that need to be accomplish daily. ADLs, are more basic tasks that are essential to independent living. IADLs, are more complex tasks that are still a necessary part of everyday life. The study subjects are MCI, so mostly independent in ADLs. Therefore, the IADL questionnaire used in the \"ADCS Prevention Instrument Project\" will be used.\n\nIADL will be assessed at baseline, 6 months and 12 months. The range score is 0-45; a higher score means that the subject is more independent.","timeFrame":"12 months"},{"measure":"Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on physical capacity","description":"Physical capacity (PC) assessment (aerobic, balance, strength) includes grip strength, 6-m walk (6MWT), timed up and go (TUG), Berg balance testing (BBS), 30 Seconds Sit To Stand Test (STS), Four Square Step Test (FSST) and the Fried frailty scale. Based on the collected data, individuals will be categorized and assigned to 1 of 3 categories: low PC (LPC), medium PC (MPC), or normal PC (NPC). Participants will receive an LPC score if either standardized 6MWT/STS/Grip score is ≤ -2 standard deviation or BBS score ≤36 or TUG score between 21-30 or FSST score \\> 15 seconds or deemed as frail assessed by the Fried scale. Participants will have an MPC score if either the standardized 6MWT/STS/Grip score is between -2 and -1.5 or BBS score is between 37-45 or the TUG score is between 15-20 or FSST score is between 10.14-14.59 or determined as pre-frail by Fried scale. All other participants will be categorized as NPC. Physical capacity will be measured at baseline and 6 months follow-up.","timeFrame":"6 months"},{"measure":"Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- Aβ.","description":"A lower amyloid beta (Aβ) 42/Aβ 40 ratio in plasma is associated with a higher risk of dementia. Aβ 42/Aβ 40 plasma ratio will be measured at baseline and 6 months followup and will be compared to assess change in ADRD-blood biomarkers between the time points.","timeFrame":"6 Months"},{"measure":"Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- P-tau181.","description":"A higher rate of P-tau181 in plasma is associated with a higher risk of dementia. Change in rate of plasma tau proteins in blood plasma from baseline to 6 months will be assessed.","timeFrame":"6 Months"},{"measure":"Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers-P-tau231.","description":"A higher rate of P-tau231associated with a higher risk of dementia. Change in rate of plasma P-tau231 proteins from baseline to 6 months will be examined.","timeFrame":"6 Months"},{"measure":"Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- T-tau.","description":"A higher rate of T-tau associated with a higher risk of dementia. Change in rate of plasma T-tau proteins in blood plasma from baseline to 6 months will be examined.","timeFrame":"6 Months"}],"publications":[{"pmid":"26711459","citation":"Love S, Miners JS. Cerebrovascular disease in ageing and Alzheimer's disease. Acta Neuropathol. 2016 May;131(5):645-58. doi: 10.1007/s00401-015-1522-0. Epub 2015 Dec 28."},{"pmid":"27350397","citation":"Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease. J Neurosci Res. 2017 Apr;95(4):943-972. doi: 10.1002/jnr.23777. Epub 2016 Jun 27."},{"pmid":"32982937","citation":"Kim HW, Hong J, Jeon JC. Cerebral Small Vessel Disease and Alzheimer's Disease: A Review. Front Neurol. 2020 Aug 25;11:927. doi: 10.3389/fneur.2020.00927. eCollection 2020."},{"pmid":"31189511","citation":"Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Ryden L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. Epub 2019 Jun 9."},{"pmid":"31924562","citation":"Gerstein HC, Hart R, Colhoun HM, Diaz R, Lakshmanan M, Botros FT, Probstfield J, Riddle MC, Ryden L, Atisso CM, Dyal L, Hall S, Avezum A, Basile J, Conget I, Cushman WC, Hancu N, Hanefeld M, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Munoz EGC, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T. The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Lancet Diabetes Endocrinol. 2020 Feb;8(2):106-114. doi: 10.1016/S2213-8587(19)30423-1. Epub 2020 Jan 7."},{"pmid":"32562683","citation":"Cukierman-Yaffe T, Gerstein HC, Colhoun HM, Diaz R, Garcia-Perez LE, Lakshmanan M, Bethel A, Xavier D, Probstfield J, Riddle MC, Ryden L, Atisso CM, Hall S, Rao-Melacini P, Basile J, Cushman WC, Franek E, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T. Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet Neurol. 2020 Jul;19(7):582-590. doi: 10.1016/S1474-4422(20)30173-3."},{"pmid":"12821276","citation":"Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH. Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a population-based cohort study. Ann Epidemiol. 2003 May;13(5):369-76. doi: 10.1016/s1047-2797(02)00464-7."},{"pmid":"19237574","citation":"Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3907-12. doi: 10.1073/pnas.0807991106. Epub 2009 Feb 23."},{"pmid":"32568367","citation":"Craft S, Raman R, Chow TW, Rafii MS, Sun CK, Rissman RA, Donohue MC, Brewer JB, Jenkins C, Harless K, Gessert D, Aisen PS. Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2020 Sep 1;77(9):1099-1109. doi: 10.1001/jamaneurol.2020.1840."},{"pmid":"28372335","citation":"Craft S, Claxton A, Baker LD, Hanson AJ, Cholerton B, Trittschuh EH, Dahl D, Caulder E, Neth B, Montine TJ, Jung Y, Maldjian J, Whitlow C, Friedman S. Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. J Alzheimers Dis. 2017;57(4):1325-1334. doi: 10.3233/JAD-161256."},{"pmid":"34101779","citation":"Kellar D, Lockhart SN, Aisen P, Raman R, Rissman RA, Brewer J, Craft S. Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease. J Prev Alzheimers Dis. 2021;8(3):240-248. doi: 10.14283/jpad.2021.14."},{"pmid":"34756135","citation":"Yoo H, Kim H, Koh I, Lee K, Ok J. Effect of Metabolic Syndrome on the Incidence of Dementia Based on National Insurance Data in Korea. Metab Syndr Relat Disord. 2022 Feb;20(1):29-35. doi: 10.1089/met.2021.0046. Epub 2021 Nov 9."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06072963"},{"nctId":"NCT06129539","title":"A Study to Assess the Efficacy, Safety, and Pharmacokinetics of Debio 4326 in Pediatric Participants With Central Precocious Puberty (LIBELULA™ Clinical Trial)","officialTitle":"LIBELULA™: An Open-label, Single-arm, Multi-center, Phase 3 Study on the Efficacy, Safety, and Pharmacokinetics of Debio 4326, a Triptorelin 12-month Formulation, in Pediatric Participants With Central Precocious Puberty","summary":"The primary objective of this study is to evaluate the efficacy of Debio 4326 in suppressing serum luteinizing hormone (LH) to prepubertal levels 52 weeks after the first Debio 4326 injection in pediatric participants with central precocious puberty (CPP).","detailedDescription":null,"peptideSlugs":["triptorelin"],"peptideNames":["Triptorelin"],"conditions":["Central Precocious Puberty"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Debiopharm International SA","slug":"debiopharm-international-sa","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":56,"dates":{"start":"2024-07-31","primaryCompletion":"2026-10","completion":"2028-02","firstPosted":"2023-11-13","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":17,"countries":["Argentina","Brazil","Chile","Mexico","United States"],"locations":[{"facility":"Rady Children's Hospital - San Diego","status":null,"city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"University of California San Francisco-Benioff Children's Hospital","status":null,"city":"San Francisco","state":"California","country":"United States","latitude":37.77493,"longitude":-122.41942},{"facility":"Prisma Health Pediatric Endocrinology","status":null,"city":"Columbia","state":"South Carolina","country":"United States","latitude":34.00071,"longitude":-81.03481},{"facility":"Instituto de Investigaciones Metabolicas (IDIM)","status":null,"city":"Buenos Aires","state":null,"country":"Argentina","latitude":-34.61315,"longitude":-58.37723},{"facility":"Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada","status":null,"city":"Buenos Aires","state":null,"country":"Argentina","latitude":-34.61315,"longitude":-58.37723},{"facility":"Centro de Investigaciones Medicas Mar del Plata","status":null,"city":"Mar del Plata","state":null,"country":"Argentina","latitude":-38.00042,"longitude":-57.5562},{"facility":"Clinica Mayo de Urgencias Medicas Cruz Blanca S.R.L","status":null,"city":"San Miguel de Tucumán","state":null,"country":"Argentina","latitude":-26.81601,"longitude":-65.21051},{"facility":"Hospital Da Criança de Brasília Jose Alencar","status":null,"city":"Brasília","state":null,"country":"Brazil","latitude":-15.77972,"longitude":-47.92972},{"facility":"Hospital Universitario Walter Cantidio","status":null,"city":"Fortaleza","state":null,"country":"Brazil","latitude":-3.71722,"longitude":-38.54306},{"facility":"Clínica de Endocrinologia e Metabologia Ltda","status":null,"city":"Lago Sul","state":null,"country":"Brazil","latitude":-15.84577,"longitude":-47.88369},{"facility":"Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS","status":null,"city":"Porto Alegre","state":null,"country":"Brazil","latitude":-30.03283,"longitude":-51.23019},{"facility":"CPQuali Pesquisa Clinica","status":null,"city":"São Paulo","state":null,"country":"Brazil","latitude":-23.5475,"longitude":-46.63611},{"facility":"Irmandade Santa Casa de São Paulo","status":null,"city":"São Paulo","state":null,"country":"Brazil","latitude":-23.5475,"longitude":-46.63611},{"facility":"Integral Pesquisa e Ensino","status":null,"city":"Votuporanga","state":null,"country":"Brazil","latitude":-20.42278,"longitude":-49.97278},{"facility":"ENDOMET","status":null,"city":"Antofagasta","state":null,"country":"Chile","latitude":-23.65094,"longitude":-70.39752},{"facility":"Hospital Clinico San Borja Arriaran (HCSBA)","status":null,"city":"Santiago","state":null,"country":"Chile","latitude":-33.45694,"longitude":-70.64827},{"facility":"Christus Latam Hub Center of Excellence and Innovation S C","status":null,"city":"Monterrey","state":null,"country":"Mexico","latitude":25.68435,"longitude":-100.31721}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Diagnosis of central precocious puberty.\n2. Onset of development of sex characteristics (i.e., breast development in girls or testicular enlargement in boys according to the Tanner method) before the age of 8 years in girls and 9 years in boys.\n3. Initially, only participants aged (a) 5 to 8 years inclusive (i.e., \\<9 years) are eligible. The Sponsor will determine based on the recommendation of the DMC following the interim analysis whether participants aged (b) 2 to 4 years inclusive (i.e., \\<5 years) and/or (c) 9 to 10 years inclusive (i.e., \\<11 years) may be recruited.\n4. Participant to receive at least 1 year of gonadotropin-releasing hormone agonist (GnRHa) therapy from study treatment start.\n5. (a) Pre-treated participants: Start of initial GnRHa therapy no later than 18 months after onset of the first signs of CPP.\n\n   (b) Treatment-naive participants: Start of Debio 4326 treatment no later than 18 months after onset of the first signs of CPP.\n6. (a) Pre-treated participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year based on historical values at the initiation of the GnRHa therapy.\n\n   (b) Treatment-naive participants: Difference between bone age (Greulich and Pyle method) and chronological age of ≥1 year.\n7. (a) Pre-treated participants: Pubertal-type LH response (LH ≥6 IU/L) following a GnRH/GnRHa stimulation test, or random non-stimulated serum LH \\>0.5 IU/L (if considered local standard of care), based on historical values prior to the initiation of GnRHa therapy.\n\n   (b) Treatment-naive participants: Pubertal-type LH response (≥6 IU/L) 30 minutes following a GnRHa \\[leuprolide acetate 20 micrograms per kilogram (μg/kg) subcutaneous injection (SC)\\] stimulation test before treatment initiation.\n8. (a) Pre-treated participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 milliliter (mL) (cubic centimeter \\[cc\\]) for boys, prior to the initiation of GnRHa therapy.\n\n   (b) Treatment-naive participants: Clinical evidence of puberty, defined as Tanner Staging ≥2 for breast development for girls and testicular volume ≥4 mL (cc) for boys.\n\nExclusion Criteria:\n\n1. Gonadotropin-independent (peripheral) precocious puberty: gonadotropin-independent gonadal or adrenal sex steroid secretion.\n2. (a) Pre-treated participants: Non-progressing, isolated premature thelarche prior to the initial GnRHa therapy.\n\n   (b) Treatment-naive participants: Non-progressing, isolated premature thelarche.\n3. Presence of an unstable intracranial tumor or an intracranial tumor potentially requiring neurosurgery or cerebral irradiation. Participants with hamartomas not requiring surgery are eligible.\n4. Any other condition or chronic illness possibly interfering with growth (e.g., renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).\n5. Other than GnRHa therapy in pre-treated participants, any ongoing treatment with a potential effect on serum levels of gonadotropins or sex steroids, or possibly interfering with growth, opioids, central nervous system \\[CNS\\] stimulants).\n6. Prior or current therapy with medroxyprogesterone acetate, growth hormone, or Insulin-like growth factor-1 (IGF-1).\n7. Diagnosis of short stature, i.e., more than 2.25 standard deviations (SD) below the mean height-for-age.\n8. Known history of seizures, epilepsy, and/or central nervous system disorders that may have been associated with seizures or convulsions.\n9. Prior (within 2 months of study treatment start) or current use of medications that have been associated with seizures or convulsions.\n10. Use of anticoagulants (heparin or coumarin derivatives).\n\nNote: Other inclusion/exclusion criteria mentioned in the protocol may apply.","minimumAge":"5 Years","maximumAge":"8 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Debio 4326","description":"Administered as an intramuscular (IM) injection"}],"primaryOutcomes":[{"measure":"Part A: Percentage of Participants With Suppression of Gonadotropin-Releasing Hormone Agonist Stimulated Serum Luteinizing Hormone (LH) to Less Than or Equal to (≤)5 International Units per Liter (IU/L)","description":null,"timeFrame":"Week 52 in Part A"}],"secondaryOutcomes":[{"measure":"Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Serious TEAEs","description":null,"timeFrame":"Up to 104 weeks"},{"measure":"Parts A and B: Number of Participants with Clinically Significant Abnormalities in Vital Signs","description":null,"timeFrame":"Up to 104 weeks"},{"measure":"Parts A and B: Change From Baseline in Body Weight","description":null,"timeFrame":"Up to 104 weeks"},{"measure":"Parts A and B: Change From Baseline in Body Mass Index","description":null,"timeFrame":"Up to 104 weeks"},{"measure":"Parts A and B: Number of Participants With Erythema, Swelling, and Induration at the Injection Site Immediately and 2 Hours After Each Debio 4326 Injection as per Investigator's Assessment","description":null,"timeFrame":"Up to 2 hours post-dose on Day 1 in both Parts A and B"},{"measure":"Parts A and B: Number of Participants With Pain at the Injection Site Immediately and 2 Hours After Each Debio 4326 Injection as per Participant's Assessment Using the Wong-Baker FACES® Pain Rating Scale","description":null,"timeFrame":"Up to 2 hours post-dose on Day 1 in both Parts A and B"},{"measure":"Parts A and B: Percentage of Participants Who do not Exhibit the Acute-on-Chronic (AOC) Phenomenon","description":null,"timeFrame":"Up to 48 hours post-dose on Day 3 in both Parts A and B"},{"measure":"Parts A and B: Percentage of Participants With Stimulated Serum LH ≤5 IU/L","description":null,"timeFrame":"Up to Week 52 in both Parts A and B"},{"measure":"Parts A and B: Percentage of Participants With Stimulated Serum LH ≤4 IU/L","description":null,"timeFrame":"Up to Week 52 in both Parts A and B"},{"measure":"Parts A and B: Number of Participants With Change in Hormone Levels","description":"The following hormones will be assessed: basal LH, follicle-stimulating hormone (FSH), estradiol, testosterone, GnRHa-stimulated LH, and GnRHa-stimulated FSH.","timeFrame":"Up to Week 52 in both Parts A and B"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06129539"},{"nctId":"NCT07225829","title":"A Trial to Investigate the Safety and Efficacy of Intra-articular 4P004 Injection in Subjects With Knee Synovitis and Osteoarthritis","officialTitle":"A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof of Concept Trial to Investigate the Efficacy and Safety of Intra-articular 4P004 in Subjects With Knee Synovitis and Osteoarthritis","summary":"This phase 2a trial is an international, multicenter, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of one single intra-articular (IA) injection of 4P004 or placebo in:\n\n* patients between 40 and 80 years of age,\n* with synovitis and grade 2 to 4 osteoarthritis (OA) of the knee according to Kellgren and Lawrence (KL) classification.","detailedDescription":null,"peptideSlugs":["liraglutide","glucagon"],"peptideNames":["Liraglutide","Glucagon"],"conditions":["Knee Osteoarthritis","Synovitis of Knee"],"keywords":["OA","Knee OA","Liraglutide","Osteoarthritis"],"conditionGroups":[{"slug":"inflammation","label":"Inflammation"}],"sponsor":{"name":"4Moving Biotech","slug":"4moving-biotech","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":129,"dates":{"start":"2025-06-17","primaryCompletion":"2026-08-28","completion":"2026-09","firstPosted":"2025-11-10","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":22,"countries":["Canada","Denmark","France","Poland","Spain","United States"],"locations":[{"facility":"Tucson Orthopaedic Institute","status":null,"city":"Tucson","state":"Arizona","country":"United States","latitude":32.22174,"longitude":-110.92648},{"facility":"Northwestern University Feinberg School of Medicine","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Skylight Health Research Burlington","status":null,"city":"Burlington","state":"Massachusetts","country":"United States","latitude":42.50482,"longitude":-71.19561},{"facility":"Durham Bone and Joint Specialists","status":null,"city":"Ajax","state":null,"country":"Canada","latitude":43.85012,"longitude":-79.03288},{"facility":"SJHC London Rheumatology Centre","status":null,"city":"London","state":null,"country":"Canada","latitude":42.98339,"longitude":-81.23304},{"facility":"G.R.M.O. (Groupe de recherche en maladies osseuses) Inc","status":null,"city":"Québec","state":null,"country":"Canada","latitude":46.81228,"longitude":-71.21454},{"facility":"Parker Institute Bispebjerg, Frederiksberg Hospital","status":null,"city":"Frederiksberg","state":null,"country":"Denmark","latitude":55.67938,"longitude":12.53463},{"facility":"Sanos Clinic Herlev","status":null,"city":"Herlev","state":null,"country":"Denmark","latitude":55.72366,"longitude":12.43998},{"facility":"CHU Montpellier","status":null,"city":"Montpellier","state":null,"country":"France","latitude":43.61093,"longitude":3.87635},{"facility":"ChU de Nice","status":null,"city":"Nice","state":null,"country":"France","latitude":43.70313,"longitude":7.26608},{"facility":"Hôpital Cochin","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Hôpital Lariboisière","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Centre Hospitalier Universitaire CHU de Reims - Hopital Maison Blanche","status":null,"city":"Reims","state":null,"country":"France","latitude":49.26526,"longitude":4.02853},{"facility":"Care Access Kraków","status":null,"city":"Krakow","state":null,"country":"Poland","latitude":50.06143,"longitude":19.93658},{"facility":"Centrum Medyczne Reuma Park","status":null,"city":"Warsaw","state":null,"country":"Poland","latitude":52.22977,"longitude":21.01178},{"facility":"MICS Centrum Medyczne Warszawa","status":null,"city":"Warsaw","state":null,"country":"Poland","latitude":52.22977,"longitude":21.01178},{"facility":"Clínica Gaias Santiago","status":null,"city":"A Coruña","state":null,"country":"Spain","latitude":43.37135,"longitude":-8.396},{"facility":"Complejo Hospitalario Universitario de A Coruna - Hospital Universitario de A Coruna","status":null,"city":"A Coruña","state":null,"country":"Spain","latitude":43.37135,"longitude":-8.396},{"facility":"HLA Clínica Vistahermosa","status":null,"city":"Alicante","state":null,"country":"Spain","latitude":38.34517,"longitude":-0.48149},{"facility":"Corporacio Sanitaria Parc Tauli - Hospital de Sabadell","status":null,"city":"Sabadell","state":null,"country":"Spain","latitude":41.54329,"longitude":2.10942},{"facility":"Clinica Nuestra Senora de la Esperanza","status":null,"city":"Santiago de Compostela","state":null,"country":"Spain","latitude":42.88052,"longitude":-8.54569},{"facility":"Hospital Quirónsalud Sagrado Corazón","status":null,"city":"Seville","state":null,"country":"Spain","latitude":37.38283,"longitude":-5.97317}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Participants who have the capacity to give informed consent and who are willing to comply with all trial related procedures and assessments.\n* Participants between 40 and 80 years of age.\n* Female participant of childbearing potential (defined as any woman unless postmenopausal for at least one year or surgically sterile) must use highly effective methods of contraception as defined in the protocol. Highly effective contraceptive measures must be continued throughout the trial until the final visit.\n* Bodyweight \\> 40 kg.\n* Body mass index (BMI) ≥ 18.5 and ≤ 35.\n* Ambulatory (single assistive devices such as canes allowed).\n* Widespread Pain Index (WPI) ≤ 4.\n* Pain NRS (0-10) \\< 4 in the contralateral knee.\n* History of OA-related pain of the TK for at least 6 months.\n* Moderate to severe pain of the TK the majority of days during the last 3 months as per participant's judgement.\n* Moderate to severe pain of the TK on the WOMAC Pain subscale prior to the Randomization visit (V2) complying with: a) Complete WOMAC Pain diary for at least 7 of the last 10 days prior to V2 (including V2/D1 rating which is mandatory), and b) Diary reported WOMAC Pain between 5 and 9 for at least 7 of the last 10 days.\n* History of insufficient pain relief, intolerance, or contraindication to NSAIDs, and at least a history of insufficient pain relief from at least one of the following therapies: a) Acetaminophen/paracetamol, b) Opioids including tramadol, or c) Corticosteroids, hyaluronate IA injections (efficacy less than 3 months according to the patient).\n* KL grade 2 to 4 on the Schuss radiograph.\n* Predominant femorotibial OA based on the OA Research Society International. (OARSI) Atlas reading (Altman \\& Gold, 2007).\n* Presence of synovitis in the TK assessed locally using PDUS, and synovial thickness of ≥ 5 mm evaluated through a longitudinal view of the suprapatellar pouch and axial views of the medial and lateral patellofemoral pouches.\n* Negative urine drug screen (performed locally): amphetamines, barbiturates, cocaine.\n* CE-MRI Central reading to confirm synovitis with a synovial Semi-Quantitative (SQ) ≥ 9 or a SQ score ≥7 with at least one site with a score ≥ 2.\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding women.\n* Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the TK (varus \\> 10°, valgus \\> 10°) by radiography.\n* Secondary OA such as joint dysplasia, aseptic osteonecrosis, joint infection, acromegaly, Paget disease, hemochromatosis, joint crystal disease or any inflammatory joint disease.\n* Any known active infections including skin infections at the site injection or increased predisposition for the development of infections.\n* Any partial knee replacement of the TK.\n* Acute fracture or IA trauma to the TK within 12 months prior to the screening visit.\n* Major knee surgery performed within the previous 12 months or planned during the trial.\n* Arthroscopy of the TK within 6 months prior to the screening visit.\n* Presence of any painful conditions that could confound accurate assessment of pain from OA in the TK, such as fibromyalgia, peripheral neuropathy or vascular insufficiency.\n* Treatment with systemic corticosteroids (other than IA) at a dose greater than 10 mg prednisone or the equivalent per day for more than 7 days within 4 weeks prior to the screening visit.\n* Treatment of the TK with any IA injection (including corticosteroids, hyaluronic acid derivatives, Platelet Rich Plasma….) within 24 weeks prior to the screening visit.\n* Any treatment with glucosamine, chondroitin sulfate, or other nutraceuticals with potential activity on OA within the previous 3 months prior to the screening visit.\n* Treatment with duloxetine for OA (allowed if given for depressive disorders at stable dose since at least 3 months before V1).\n* Any significant psychiatric illness unless well controlled since at least 6 months.\n* Current treatment with combination of insulin and liraglutide (Xultophy®) or with GLP-1 agonist administered once a week (semaglutide, dulaglutide).\n* High-risk of bleeding.\n* Congestive Heart Failure stage III or IV in the New York Heart Association classification.\n* History or current diagnosis of electrocardiogram ECG abnormalities indicating significant safety risk (such as ischemia, significant cardiac arrhythmias).\n* Glycemia \\< 4.4 mmol/L (or 80 mg/dL) at screening.\n* Clinically significant abnormal laboratory test at screening, in particular: haemoglobin \\<10 g/dL, white blood cell \\<3000/µL (3.0 Giga/L), absolute neutrophil count \\<1000/µL (1.0 Giga/L), platelets count \\<100,000/µL (100 Giga/L), alanine aminotransferase or aspartate aminotransferase \\>2.5 upper limit of normal (ULN), total bilirubin \\>1.5 ULN, lipasemia \\>1 ULN.\n* Estimated glomerular filtration rate (eGFR) \\<60 mL/min/1.73 m2, using Chronic Kidney Disease - EPIdemiology (CKD EPI) 2021 Formula.\n* Any other abnormal laboratory results that the Investigator believes should preclude the subject's participation in the trial.\n* History of hypersensitivity to IMP or excipients (liraglutide or disodium phosphate dihydrate, propylene glycol, phenol).\n* Any contraindication for MRI (cardiac pacemaker, deep brain stimulators, intraocular metal, cerebral aneurysm clips, recent stents, cochlear implants, neurostimulators and implantable pumps) or inability to undergo MRI (e.g., body size, leg not fitting in the coil, claustrophobia).\n* History of hypersensitivity reactions to a gadolinium-based contrast agent.\n* Any CE-MRI Central reading additional diagnoses: posterior meniscal root tears, subchondral insufficiency fractures, osteonecrosis, malignant bone marrow infiltration, solid tumours, and traumatic fracture or bone bruise using ROAMES (Roemer et al., 2020).\n* Previous participation in clinical research with a disease-modifying OA drug during the last 2 years.\n* Participation in an interventional clinical research trial within 3 months before screening.\n* Participants who, in the investigator's judgement, are at risk of falling.\n* Participants with a history, or current diagnosis, of pancreatitis, thyroid cancer (including medullary thyroid carcinoma), multiple endocrine neoplasia type-2 (MEN2), diabetic ketoacidosis, type-1 diabetes mellitus (T1DM), inflammatory bowel disease, or diabetic gastroparesis.\n* Participants currently, or within the last 10 days, taking any anticoagulant treatment.","minimumAge":"40 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"4P004","description":"Single intra-articular injection in the knee joint"},{"type":"DRUG","name":"Placebo (NaCl 0.9%)","description":"Single intra-articular injection in the knee joint"}],"primaryOutcomes":[{"measure":"Change from Baseline at Week 4 in the weekly average of Target Knee (TK) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore","description":"The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score.\n\nHigher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.","timeFrame":"Baseline and Week 4"}],"secondaryOutcomes":[{"measure":"Change from Baseline at Week 2, Week 6, Week 8, Week 10 and Week 12 in the weekly average of TK (Target Knee) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore","description":"The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score.\n\nHigher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.","timeFrame":"Baseline, Week 2, Week 6, Week 8, Week 10 and Week 12"},{"measure":"Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the NRS (Numeric Rating Scale) pain (scale 0-10) in a nominated pain aggravating activity","description":"The numeric rating scale (NRS) is a pain screening tool, commonly used to assess pain severity at that moment in time, using a 0-10 scale, with zero meaning \"no pain\" and 10 meaning \"the worst pain imaginable.","timeFrame":"Baseline, Week 2, Week 4, Week 8 and Week 12"},{"measure":"Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in WOMAC (Western Ontario and McMaster Universities Arthritis Index) subscores and total score","description":"The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score.\n\nHigher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.","timeFrame":"Baseline, Week 2, Week 4, Week 8 and Week 12"},{"measure":"Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the Patient Global Assessment of Osteoarthritis (PGA-OA)","description":"The PGA-OA is a 1-item questionnaire designed to assess the participant's impression of disease severity adapted from Guy et al., 1976, to the specific disease as a Patient-reported Outcome measurement \"Considering all the ways your knee osteoarthritis affects you, how are you doing these last seven days ?\".\n\nPGA-OA is measured on a 5-point Likert scale, with higher scores indicating worse symptoms (1= \"very good\" to 5 = \"very poor\").","timeFrame":"Baseline, Week 2, Week 4, Week 8 and Week 12"},{"measure":"Percentage (%) of OMERACT-OARSI Responders at Week 2, Week 4, Week 8 and Week 12","description":null,"timeFrame":"Week 2, Week 4, Week 8 and Week 12"},{"measure":"Incidence and severity of TEAEs (Treatment-Emergent Adverse Events) during the trial","description":null,"timeFrame":"From randomization to end of trial, up to 12 weeks"},{"measure":"Absolute changes from Baseline in clinical laboratory assessment - hematology parameter: total blood cells count (in cell/L)","description":null,"timeFrame":"From randomization to end of trial (up to 12 weeks)"},{"measure":"Absolute changes from Baseline in clinical laboratory assessments - hematology parameter: hemoglobin (in g/L)","description":null,"timeFrame":"From randomization to end of trial (up to 12 weeks)"},{"measure":"Absolute changes from Baseline in clinical laboratory assessment - blood chemistry: AST (in U/L)","description":null,"timeFrame":"From randomization to end of trial (up to 12 weeks)"},{"measure":"Absolute changes from Baseline in clinical laboratory assessment - blood chemistry: ALT (in U/L)","description":null,"timeFrame":"From randomization to end of trial (up to 12 weeks)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07225829"},{"nctId":"NCT07349641","title":"A Study of Weight Loss Intervention With Tirzepatide and Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer","officialTitle":"Tirzepatide With Progestin Intrauterine Device to Treat Endometrial Hyperplasia and Grade 1 Endometrial Cancer in Overweight and Obese Women","summary":"This phase II trial studies whether adding tirzepatide injections to a levonorgestrel intrauterine device (LNG-IUD) improves pathologic response (absence of cancer cells in tissue samples after treatment) in women with endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer who are overweight or obese. Endometrial cancer occurrence has continued to rise in the United States. Over half of endometrial cancer cases are thought to be attributable to being overweight and obese, and the risk relationship appears to be weight dependent. AH/EIN is a precancerous condition of the endometrium (the uterus or womb) where the lining of the uterus grows abnormally thick, and the cells become abnormal. Women with this thickening have a higher-than-average risk of developing endometrial cancer if left untreated. The usual approach for patients who have AH/EIN and grade 1 endometrial cancer is the removal of the uterus. While surgical treatment is generally safe and effective, it may not be the best approach for some patients. The LNG-IUD is a small, T-shaped device inserted into the uterus that releases the hormone levonorgestrel, a progestin, which counteracts the effects of estrogen in the endometrium. Tirzepatide is a dual glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonist which has been shown to drive weight loss. Adding tirzepatide injections to LNG-IUD may help overweight or obese women with AH-EIN or grade 1 endometrial cancer lose weight, which may improve pathologic response.","detailedDescription":"PRIMARY OBJECTIVE:\n\nI. To determine the proportion of pathological complete response (pCR) on endometrial biopsy (EMB) at 26 weeks among patients receiving combined treatment with tirzepatide (dosed weekly) and levonorgestrel intrauterine device (LNG-IUD) for management of endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and grade 1 endometrioid endometrial cancer in overweight or obese women compared to historical controls who received LNG-IUD alone.\n\nSECONDARY OBJECTIVES:\n\nI. To determine the proportion of participants who achieve sustained pathologic complete response on EMB at 52 weeks (12 months) compared to historical controls.\n\nII. To estimate the time to complete response and duration of response, up to 52 weeks (12 months) compared to historical controls.\n\nIII. To determine the rate of hyperplasia persistence and progression to endometrial cancer at 26 and 52 weeks (6 and 12 months) compared to historical controls.\n\nIV. To estimate percent change in cell proliferation (Ki-67+) at 12, 26, 39 and 52 weeks compared to historical controls and baseline.\n\nV. To estimate percent change in hemoglobin A1C (HbA1C) at 12, 26, 39 and 52 weeks compared to baseline.\n\nVI. To estimate percent weight change every 4 weeks up to week 20 and then at weeks 26, 39 and 52 compared to baseline.\n\nVII. To estimate percent change in fasting blood glucose every 4 weeks up to week 20 and then at weeks 26, 39, and 52 compared to baseline.\n\nEXPLORATORY OBJECTIVES:\n\nI. To investigate the effect of GLP-1 agonism on the endometrial immune microenvironment at 12, 26, 39 and 52 weeks compared to baseline.\n\nII. To investigate the effect of GLP-1 agonism on systemic inflammation and metabolic markers at 12 26, 39 and 52 weeks compared to baseline.\n\nIII. To investigate weight independent effects of GLP-1 agonism on cell proliferation (Ki-67+) at 12, 26, 39 and 52 weeks compared to baseline.\n\nIV. To investigate the effect of tirzepatide and LNG-IUD on treatment response based on molecular ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification at 26 and 52 weeks.\n\nOUTLINE:\n\nAfter LNG-IUD placement at baseline or on day 0, participants then self-inject tirzepatide subcutaneously (SC) once a week (QW) for 26 weeks in the absence of disease progression or unacceptable toxicity. Patients who qualify for tirzepatide or another weight loss medication as determined by primary provider may continue to receive treatment beyond 26 weeks as per standard of care.\n\nAfter completion of study treatment, patients are followed up at weeks 30, 39, and 52.","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia","FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":55,"dates":{"start":"2026-07-06","primaryCompletion":"2028-12-31","completion":"2029-12-31","firstPosted":"2026-01-20","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":3,"countries":["United States"],"locations":[{"facility":"Northwestern University","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Lyndon Baines Johnson General Hospital","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327},{"facility":"UT MD Anderson Cancer Center","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Women who have a pathologic diagnosis of AH/EIN or grade 1 endometrioid endometrial cancer confirmed on dilation and curettage (D\\&C) and desire non-surgical management, who are overweight (body mass index \\[BMI\\] ≥ 27 kg/m\\^2) with a weight-related comorbidity (hypertension, type 2 diabetes, or high cholesterol) or obese (BMI ≥ 30 kg/m\\^2) with or without weight-related comorbidities\n* Prior progesterone treatment for conditions other than AH/EIN or endometrial cancer is allowed, but a 28-day washout period is required before levonorgestrel IUD placement. If archival tissue is available from prior to any progesterone treatment but after the diagnosis of AH/EIN/EC, the washout period is not needed\n* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of tirzepatide in participants \\< 18 years of age, children and adolescents \\< 18 years of age are excluded from this study but will be eligible for future pediatric trials, if applicable\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For participants with a history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load\n* Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible\n* Ability to comply with EMB every 3 months\n* Women currently using oral hypoglycemic agents (e.g., metformin) are eligible for the study\n* Ability to understand and the willingness to sign a written informed consent document in English or Spanish\n\nExclusion Criteria:\n\n* Women with grade 2-3 endometrioid, or women with serous, clear cell, mucinous, squamous, transitional cell, sarcomas, or carcinosarcoma histology\n* Evidence of extrauterine spread of disease on imaging or during surgical evaluation\n* Participants may not be receiving any other investigational agents or anticancer therapies (including chemotherapy, radiation therapy, hormonal, or antibody-based therapy). Prior treatment should have a minimum washout period of 14 days\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the levonorgestrel IUD or any GLP-1 agonist\n* Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study. Because of this, a pregnancy test is part of the screening for the study and women who are pregnant or planning pregnancy within 6 months after the end of the study will be excluded. The LNG-IUD is an Food and Drug Administration (FDA)-approved contraceptive agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.\n\nBecause there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with tirzepatide, breastfeeding should be discontinued if the mother is treated with tirzepatide\n\n* Women who have any severe and/or uncontrolled medical conditions such as:\n\n  * Unstable angina pectoris, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease,\n  * Symptomatic congestive heart failure of New York Heart Association class III or IV,\n  * Active (acute or chronic) or uncontrolled severe infection (not responding to antibiotics), liver diseases such as cirrhosis and decompensated liver disease,\n  * Known severely impaired lung function (spirometry and diffusion capacity of the lung for carbon monoxide \\[DLCO\\] 50% or less of normal and oxygen \\[O2\\] saturation 88% or less at rest on room air), or\n  * Active, bleeding diathesis\n* Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin\n* Active (acute or chronic) or uncontrolled severe infections (not responding to antibiotics), including acute pelvic inflammatory disease\n* Congenital or acquired uterine anomaly which distorts the uterine cavity\n* Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use one additional highly effective method of contraception in addition to the LNG-IUD during the study and 8 weeks after. Acceptable highly effective contraception methods include a combination of any of the following:\n\n  * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;\n  * Total abstinence or;\n  * Male sterilization;\n  * Female bilateral tubal ligation or bilateral salpingectomy Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy or tubal ligation at least six weeks prior to study initiation. When the diagnosis of menopause is unclear based on patient history, we will assess follicle-stimulating hormone \\\\ (FSH) levels for confirmation. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential\n* Tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia (MEN) 2A or 2B. Such women will be excluded\n* Participants taking any other prescription medication intended to induce weight loss (i.e., orlistat, phentermine-topiramate, naltrexone-bupropion). A 28-day washout period is required if such women want to enter the study\n* Participants on active intermittent fasting\n* Participants currently using insulin for glucose control\n* Participants who have previously used any glucagon-like peptide (GLP) medications (liraglutide, semaglutide, dulaglutide, exenatide), whether oral or injectable\n* Participants diagnosed with Lynch Syndrome","minimumAge":"18 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"OTHER","name":"Medical Device Usage and Evaluation","description":"Undergo LNG-IUD placement"},{"type":"DRUG","name":"Tirzepatide","description":"Given SC"}],"primaryOutcomes":[{"measure":"Weighted pathological complete response (pCR)","description":"Proportion of pCR at 26 weeks among patients receiving combined treatment with tirzepatide and levonorgestrel intrauterine device (LNG-IUD) compared to historical controls who received LNG-IUD alone.","timeFrame":"At 26 weeks"}],"secondaryOutcomes":[{"measure":"Proportion of participants who achieve pCR on endometrial biopsy","description":"Will be compared to historical controls.","timeFrame":"At 52 weeks"},{"measure":"Time to complete response and duration of response","description":"Will be compared to historical controls.","timeFrame":"Up to 52 weeks"},{"measure":"Rate of hyperplasia persistence and progression to EC","description":"Will be compared to historical controls as assessed by standard pathologic criteria.","timeFrame":"At 26 and 52 weeks"},{"measure":"Percent change in cell proliferation","description":"Will assess Ki67 within pre-treatment biopsy and post-treatment biopsies. Will also compare with historical controls.","timeFrame":"At baseline and 12, 26, 39, and 52 weeks"},{"measure":"Percent change in hemoglobin A1C","description":"Will be measured by means of commercially available assays.","timeFrame":"At baseline and weeks 12, 26, 39, and 52"},{"measure":"Percent weight change","description":"Will summarize percent changes from baseline.","timeFrame":"Every 4 weeks up to week 20 and at weeks 26, 39, and 52"},{"measure":"Percent change in fasting blood glucose","description":"Will summarize percent changes from baseline.","timeFrame":"Every 4 weeks up to week 20 and at weeks 26, 39, and 52"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07349641"},{"nctId":"NCT07727473","title":"Preoperative Semaglutide Prior to Radical Prostatectomy","officialTitle":"A Prospective, Open-label, Exploratory Interventional Trial of Preoperative Semaglutide Prior to Radical Prostatectomy for Intermediate-risk Localized Prostate Cancer","summary":"In this exploratory, single-arm, nonrandomized trial, the impact of the preoperative utilization of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) semaglutide prior to radical prostatectomy in participants with intermediate risk prostate cancer will be investigated. Semaglutide will be administered according to the FDA-approved label for chronic weight management and participants will be dosed with a weekly subcutaneous injection. The primary aim of this trial is to explore the tumor biological activity of semaglutide in these participants. The trial will also evaluate the safety and tolerability of this preoperative treatment, along with the impact on physiologic/metabolic parameters.","detailedDescription":null,"peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Prostate Cancer"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Banner Health","slug":"banner-health","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["EARLY_PHASE1"],"slugs":["early-phase-1"],"labels":["Early Phase 1"],"label":"Early Phase 1","highest":0.5},"studyType":"INTERVENTIONAL","enrollment":20,"dates":{"start":"2026-07","primaryCompletion":"2028-05","completion":"2029-05","firstPosted":"2026-07-27","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Banner MD Anderson Cancer Center at Gateway","status":null,"city":"Gilbert","state":"Arizona","country":"United States","latitude":33.35283,"longitude":-111.78903}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Male participants aged ≥18 years\n* Biopsy-proven intermediate-risk localized prostate cancer per NCCN risk stratification criteria\n* Planning to undergo radical prostatectomy, and surgical delay of 3-6 months is deemed appropriate by the investigator\n* Body mass index (BMI) \\>35 kg/m²\n* No prior exposure to androgen deprivation therapy or androgen receptor pathway inhibitors\n\nExclusion Criteria:\n\n* Prostate cancer risk classification other than intermediate risk\n* Hemoglobin A1c (HbA1c) \\>9%\n* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)\n* Baseline gastroparesis, dysphagia, or other significant gastrointestinal disease limiting oral intake\n* Current or recent (within 12 months) exposure to GLP-1 receptor agonist therapy\n* Delay of radical prostatectomy by 3-6 months is not deemed advisable by the investigator","minimumAge":"18 Years","maximumAge":null,"sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide 2.4 mg","description":"Semaglutide will be administered as a weekly subcutaneous injection. The dose will be titrated according to the FDA-approved labeling, starting at 0.25 mg once weekly and increasing as tolerated to a target maintenance dose of up to 2.4 mg once weekly. Treatment will continue for 3 to 6 months prior to planned radical prostatectomy."}],"primaryOutcomes":[{"measure":"Change in Caspase-3 (CC3) activation between baseline biopsy and radical prostatectomy specimen","description":"Measured via immunohistochemistry on prostate biopsy tissue and radical prostatectomy specimens; change assessed between pre-treatment biopsy and surgical specimen.","timeFrame":"Baseline (pre-treatment biopsy) through radical prostatectomy, assessed up to 6 months"},{"measure":"Change in Ki-67 proliferative index between baseline biopsy and radical prostatectomy specimen","description":"Percentage of Ki-67 expression measured via immunohistochemistry; compared between pre-treatment biopsy and radical prostatectomy specimen.","timeFrame":"Baseline through radical prostatectomy, assessed up to 6 months"},{"measure":"Change in Gleason score from biopsy to prostatectomy specimen","description":"Pathologic Gleason Score assessed using the Gleason Grading System (score range 6-10). Higher scores indicate more aggressive prostate cancer pathology.","timeFrame":"Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months"},{"measure":"Change in Decipher genomic score in prostate tumor tissue","description":"Decipher Genomic Classifier Score (continuous scale ranging from 0 to 1.0). Higher scores indicate greater risk of adverse oncologic outcomes.","timeFrame":"Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months"}],"secondaryOutcomes":[{"measure":"Incidence of postoperative complications following radical prostatectomy assessed by Clavien-Dindo classification","description":"Postoperative complications graded using the Clavien-Dindo Classification System (Grade I-V). Higher grades indicate more severe postoperative complications.","timeFrame":"30 days and 90 days following radical prostatectomy"},{"measure":"Incidence of Grade 2 or higher adverse events as assessed by CTCAE criteria","description":"Treatment-emergent adverse events graded according to CTCAE criteria; includes events occurring during semaglutide treatment and postoperative follow-up.","timeFrame":"From initiation of semaglutide through 90 days post-radical prostatectomy"},{"measure":"Change in body weight","description":"Measured in kilograms and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"},{"measure":"Change in body mass index (BMI)","description":"BMI (kg/m²) calculated and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"},{"measure":"Change in hemoglobin A1c (HbA1c)","description":"Measured via blood testing and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"},{"measure":"Change in c-peptide levels","description":"Measured via blood testing and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"},{"measure":"Change in high-sensitivity C-reactive protein (hsCRP)","description":"Measured via blood testing and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"},{"measure":"Change in lipid profile parameters","description":"Includes total cholesterol, LDL, HDL, and triglycerides measured by blood testing and compared between baseline and preoperative assessment.","timeFrame":"Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07727473"},{"nctId":"NCT07728318","title":"Efficacy, Safety, and Treatment Satisfaction of Once-Weekly Tirzepatide in Obese Type 2 Diabetic Patients","officialTitle":"Efficacy, Safety and Treatment Satisfaction of Once Weekly Tirzepatide in Obese Type 2 Diabetic Patients at a Tertiary Care Centre","summary":"Type 2 Diabetes Mellitus (T2DM) is a progressive metabolic disease, often compounded by obesity, that leads to serious long-term health complications. While traditional antidiabetic medications help manage blood sugar, many patients continue to struggle with uncontrolled diabetes and excess weight. Newer therapies, such as dual GIP/GLP-1 receptor agonists like Tirzepatide, have demonstrated significant efficacy in lowering blood glucose (HbA1c) and body weight in global clinical trials. However, real-world data regarding its efficacy, safety, and patient-reported satisfaction in South Asian populations, particularly in Pakistan, remains limited. This 6-month, quasi-experimental interventional study aims to compare the clinical outcomes and patient-reported satisfaction of once-weekly subcutaneous Tirzepatide (combined with standard oral antidiabetic therapy) versus standard therapy alone in obese patients with Type 2 Diabetes. A total of 52 eligible participants will be randomly allocated into two groups. Group 1 will receive standard oral antidiabetic treatment, while Group 2 will receive once-weekly Tirzepatide with dose escalation (starting at 2.5 mg monthly, increasing to 5 mg, and maintaining at 7.5 mg) alongside standard treatment. Primary evaluations will measure changes in HbA1c and body weight from baseline to 6 months. Secondary objectives include monitoring the frequency and severity of gastrointestinal side effects fortnightly and evaluating patient treatment satisfaction at 6 months using the validated Diabetes Treatment Satisfaction Questionnaire (DTSQ).","detailedDescription":null,"peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Type 2 Diabetes Mellitus (T2DM), Obesity, Overweight"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Akhtar Saeed Medical and Dental College","slug":"akhtar-saeed-medical-and-dental-college","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":52,"dates":{"start":"2026-08-12","primaryCompletion":"2027-01-12","completion":"2027-05-12","firstPosted":"2026-07-27","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Male and female patients aged 30 to 80 years with diagnosed Type 2 Diabetes Mellitus.\n2. Uncontrolled diabetes with HbA1c ≥ 7.0%.\n3. Obesity defined as Body Mass Index (BMI) ≥ 25 kg/m² (Asian population threshold) or waist circumference \\> 90 cm in men or \\> 80 cm in women.\n4. History of taking oral antidiabetic drugs (OADs) for \\> 1 year.\n\nExclusion Criteria:\n\n1. Patients currently or previously taking GLP-1 receptor agonists or weight loss medications.\n2. Patients currently receiving insulin therapy.\n3. Patients taking DPP-4 inhibitors.\n4. Pregnant or lactating females.","minimumAge":"30 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"OTHER","name":"Tirzepatide + Standard Therapy (Intervention Group)","description":"Administered subcutaneously once weekly with dose escalation:\n\nMonth 1: 2.5 mg once weekly Month 2: 5 mg once weekly Months 3 to 6: Maintenance dose of 7.5 mg once weekly'"},{"type":"OTHER","name":"Standard Oral Antidiabetic Drugs (OADs)","description":"Standard oral antidiabetic therapy including Metformin (500mg, 1000mg, or 1500mg daily) with or without SGLT2 inhibitors (Dapagliflozin or Empagliflozin) maintained throughout the 6-month study period"}],"primaryOutcomes":[{"measure":"Change in Glycemic Control (HbA1c)","description":"Mean change in HbA1c percentage from baseline to evaluate efficacy in glycemic control (a reduction of ≥1% is defined as clinically effective).","timeFrame":"Baseline, 3 months, and 6 months"},{"measure":"Change in Body Weight","description":"Mean percentage change in body weight from baseline (a weight reduction of ≥5% is defined as clinically effective).","timeFrame":"Baseline and monthly up to 6 months"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07728318"},{"nctId":"NCT07728383","title":"A Proof-of-Concept Study to Evaluate Topical-Lingual Semaglutide in Adults With Obesity","officialTitle":"A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Topical-Lingual Semaglutide (T-L Semaglutide) in Adults With Obesity","summary":"This study investigates the Topical-Lingual (T-L) delivery of semaglutide, a GLP-1 receptor agonist (GLP-1RA), via an oral liquid emulsion formulation as a Proof-of-Concept for the T-L delivery of metabolic hormones in general. GLP-1 is a gut-derived hormone that induces satiation through hypothalamic pathways.","detailedDescription":"This study investigates the Topical-Lingual (T-L) delivery of semaglutide, a GLP-1 receptor agonist (GLP-1RA), via an oral liquid emulsion formulation as a Proof-of-Concept for the T-L delivery of metabolic hormones in general. GLP-1 is a gut-derived hormone that induces satiation through hypothalamic pathways. This study will compare the efficacy (weight loss), safety and tolerability of oral versus topical-lingual semaglutide versus placebo. Pharmacokinetic data (semaglutide Cmax) will be compared across the 3 arms.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Obesity & Overweight"],"keywords":["Obesity"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Gila Therapeutics, Inc.","slug":"gila-therapeutics-inc","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":40,"dates":{"start":"2026-06-17","primaryCompletion":"2027-05","completion":"2027-05","firstPosted":"2026-07-27","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Clinical Research Institute of Minnesota","status":"RECRUITING","city":"Minneapolis","state":"Minnesota","country":"United States","latitude":44.97997,"longitude":-93.26384}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Body Mass Index 30 to 45\n\nExclusion Criteria:\n\n* Type 2 Diabetes Mellitus\n* Multiple Endocrine Neoplasia Type 2\n* Medullary thyroid cancer","minimumAge":"18 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Semaglutide 6 mg liquid emulsion formulation","description":"Semaglutide 6 mg liquid emulsion formulation daily"},{"type":"DRUG","name":"Wegovy® (semaglutide) Tablet","description":"Wegovy® (semaglutide) Tablet 25 mg daily"},{"type":"DRUG","name":"Placebo liquid emulsion formulation","description":"Placebo liquid emulsion formulation daily"}],"primaryOutcomes":[{"measure":"Percent body weight change from baseline","description":"Percentage change in body weight at 24 weeks from baseline by calibrated scale.","timeFrame":"24 weeks"}],"secondaryOutcomes":[{"measure":"Change in hemoglobin A1c","description":"Percentage and absolute change in hemoglobin A1c from baseline to 24 weeks.","timeFrame":"24 weeks"},{"measure":"Comparison of plasma semaglutide levels (Cmax) in 3 arms of study","description":"Maximum Plasma Concentration (Cmax) of semaglutide measured with verified analytic method across the 3 arms of the study","timeFrame":"16 weeks"},{"measure":"Proportion of subjects with 5% and 10% body weight loss","description":"Proportion of subjects with 5% and 10% body weight loss at 24 weeks versus baseline on a calibrated scale","timeFrame":"24 weeks"},{"measure":"Nausea Severity Scale","description":"NSS measures chronic nausea severity and ranges from 0 - 4 (mean of all 4 items). Higher scores mean a worse outcome.","timeFrame":"24 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07728383"},{"nctId":"NCT07728812","title":"Pragmatic Trial to Study the Cost-Effectiveness of MyPhenome-RX Test to Guide Anti-Obesity Pharmacotherapy","officialTitle":"Pragmatic Trial to Study the Cost-Effectiveness of MyPhenome-RX Test to Guide Anti-Obesity Pharmacotherapy (PhenoRX Pragmatic Trial)","summary":"A pragmatic, randomized, parallel-arm, controlled study of weight loss outcomes using AOMs guided by MyPhenome test.","detailedDescription":null,"peptideSlugs":["tirzepatide","semaglutide"],"peptideNames":["Tirzepatide","Semaglutide"],"conditions":["Obesity & Overweight"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Phenomix Sciences","slug":"phenomix-sciences","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":424,"dates":{"start":"2026-09-01","primaryCompletion":"2028-07-01","completion":"2029-01-01","firstPosted":"2026-07-27","resultsPosted":null,"lastUpdated":"2026-07-27"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adults - age 18 or older\n* obesity (BMI ≥ 30 kg/m2) without obesity related diseases (ORDs). Or obesity (BMI ≥ 27 kg/m2) with obesity related diseases (ORDs).\n* Mayo Clinic employee or dependent\n* Referred to Community Internal Medicine Weight Management Program\n\nExclusion Criteria:\n\n* Pregnancy or currently breast feeding.\n* No contraindications to the weight loss medications: Phentermine-Topiramate Extended Release (Qsymia®); Oral naltrexone extended-release/bupropion extended-release (NBSR; Contrave®, Mysimba™); Liraglutide (Saxenda®), Semaglutide (Wegovy®), and Tirzepatide (Zepbound®).","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"GENETIC","name":"Genetic Test","description":"The MyPhenome test is a genetic and clinical assessment that classifies individuals into biologically defined obesity phenotypes to guide personalized treatment. Using a saliva DNA sample combined with brief clinical inputs, the test predicts whether a patient has abnormalities in high CTSGRS (\"Hungry Brain\"), low CTSGRS (\"Hungry Gut\"), or hedonic eating (\"Emotional Hunger\")."},{"type":"DRUG","name":"Anti-Obesity Medication (AOM) treatment","description":"Available AOMs will be: GLP-1 Receptor Agonists (semaglutide or tirzepatide), Phentermine-Topiramate ER, and naltrexone-bupropion SR"}],"primaryOutcomes":[{"measure":"Total Body Weight Loss (TBWL) at 6 Months %","description":"TWBL% at 6 months","timeFrame":"6-Months"}],"secondaryOutcomes":[{"measure":"TBWL% at 3 Months","description":"TBWL% at 3 Months","timeFrame":"3-months"},{"measure":"TBWL% at 9 Months","description":"TBWL% at 9 Months","timeFrame":"9-Months"},{"measure":"TBWL% at 12 Months","description":"TBWL% at 12 Months","timeFrame":"12-Months"},{"measure":"TBWL% at 18 Months","description":"TBWL% at 18 Months","timeFrame":"18-Months"},{"measure":"TBWL% at 24 Months","description":"TBWL% at 24 Months","timeFrame":"24-Months"},{"measure":"Degree of Treatment Response","description":"6-Months: non-responsive (\\<3% TBWL), partial responsive (3%-15% TBWL), successful (\\>15%-20% TBWL) and highly successful (\\>20% TBWL)","timeFrame":"6-Months"},{"measure":"Cost of Treatment","description":"Cost of Treatment","timeFrame":"3, 6, 9, 12, 18, 24 Months"},{"measure":"Cost-Effectiveness","description":"Cost-Effectiveness\n\nPharmacy resource utilization data will be collected during the study. Pharmacotherapy costs will be directly compared between control and intervention groups and compared to weight loss outcomes.","timeFrame":"3, 6, 9, 12, 18, 24 Months"},{"measure":"Patient Satisfaction","description":"Client Satisfaction Questionnaire (CSQ-8): Given the design of the study, we will measure and evaluate patient satisfaction with a program of care rather than satisfaction with a specific medication. The satisfaction with the program will be evaluated with the adapted Client Satisfaction Questionnaire (CSQ-8). This is an 8-item measure that captures overall satisfaction with the care received, including perceived quality, whether care met patient needs, and willingness to recommend the program (each item score 1-4). The items will be lightly adapted to refer to weight management care with a total score ranging from 8 to 32 .","timeFrame":"3, 6, 9, 12, 18, 24 Months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07728812"},{"nctId":"NCT06259097","title":"Different Medications to Induce Labor","officialTitle":"Misoprostol Versus Pitocin for Induction of Labor in Patients With BMI > 30: A Randomized Controlled Trial","summary":"This is a randomized controlled trial examining whether the use of misoprostol or pitocin, in combination with a foley catheter, is more effective at inducing labor in patients with a gravid BMI that is considered obese.","detailedDescription":"This randomized controlled trial will include patients with a BMI greater than 30 at the time of admission for their induction of labor. Patients will be randomized to either misoprostol or Pitocin to begin induction of labor, alongside the standard foley catheter, and the primary outcome of interest will be length of time from start of induction until delivery.","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["Pregnancy","Labor"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Icahn School of Medicine at Mount Sinai","slug":"icahn-school-of-medicine-at-mount-sinai","class":"OTHER"},"collaborators":[{"name":"Bronx Care Health System","slug":"bronx-care-health-system","class":"OTHER"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":281,"dates":{"start":"2024-07-02","primaryCompletion":"2026-08","completion":"2026-08","firstPosted":"2024-02-14","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"Mount Sinai Hospital","status":"RECRUITING","city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Bronx Care Health System","status":"RECRUITING","city":"The Bronx","state":"New York","country":"United States","latitude":40.84985,"longitude":-73.86641}],"eligibility":{"criteria":"Inclusion Criteria:\n\n\\- Pregnant patient presenting to labor \\& delivery for induction of labor with a BMI \\> = 30\n\nExclusion Criteria:\n\n\\- Pregnant patient presenting to labor \\& delivery for induction of labor with BMI \\< 30","minimumAge":"18 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Misoprostol","description":"25 mcg vaginally every 6 hours"},{"type":"DRUG","name":"Pitocin","description":"3-6 mL intravenously every hour"}],"primaryOutcomes":[{"measure":"Time from induction to delivery","description":"Simple measure calculating time from start of induction until delivery of neonate.","timeFrame":"start of induction until delivery"}],"secondaryOutcomes":[{"measure":"Delivery outcome","description":"Simple determination whether patient had a vaginal delivery or delivered by cesarean section.","timeFrame":"at delivery"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06259097"},{"nctId":"NCT06379217","title":"NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.","officialTitle":"A Phase I, Open-label, Multi-center Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.","summary":"The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen (PSMA), Somatostatin Receptor 2 (SSTR2), and Gastrin Releasing Peptide Receptor (GRPR) between the baseline and following targeted radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).","detailedDescription":"The screening period for each participant includes imaging with 3 radioligand imaging (RLI) compounds to assess expression level of PSMA, SSTR2 and GRPR. Participants will be assigned to the radioligand treatment (RLT) corresponding to their predominantly expressed target based on blinded independent central review (BICR). During the treatment period, participants will receive up to 6 cycles of the assigned RLT, corresponding to a total dose of 44.4 GBq (+/-10%) for \\[177Lu\\]Lu-PSMA-617 or \\[177Lu\\]Lu-DOTA-TATE , and 55.5 GBq (+/-10%) for \\[177Lu\\]Lu-NeoB. No crossover to a different type of RLT is allowed.\n\nAt least six weeks after receiving the first cycle of RLT, participants must be scanned again with up to 3 RLIs but must be scanned, with at least with one RLI corresponding to the received RLT, which is recommended to be performed first. All post-baseline PET/CT scans should be performed using the same PET/CT imaging agent and same PET/CT camera, acquisition and reconstruction protocols as used for screening PET/CT for the participant.\n\nThe post-treatment follow-up period consists of a 42-days Safety follow-up visit.\n\nThe planned duration of treatment is up to 36 weeks for all treatment arms in this study, with treatment given every 6 weeks ±7 days. Participants may be discontinued from treatment earlier due to unacceptable toxicity or disease progression, and/or at the discretion of the Investigator or the participant.\n\nProtocol Amendment 7 follows the Sponsor's business decision to halt enrollment on 05-Jan-2026. The premature closure of the trial was not driven by any safety concerns identified in the study to date.","peptideSlugs":["degarelix"],"peptideNames":["Degarelix"],"conditions":["Metastatic Neuroendocrine Prostate Cancer"],"keywords":["[68Ga]Ga-PSMA-11","[177Lu]Lu-PSMA-617","[68Ga]Ga-DOTA-TATE","[177Lu]Lu-DOTA-TATE","[68Ga]Ga-NeoB","[177Lu]Lu-NeoB","Neuroendocrine prostate cancer (NEPC)","Metastatic Neuroendocrine Prostate Cancer (mNEPC)","Radioligand Imaging (RLI)","Radioligand Therapy (RLT)","Prostate-specific membrane antigen (PSMA)","Somatostatin Receptor 2 (SSTR2)","Gastrin Releasing Peptide Receptor (GRPR)","Phase 1"],"conditionGroups":[{"slug":"longevity","label":"Longevity"}],"sponsor":{"name":"Novartis","slug":"novartis","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":31,"dates":{"start":"2024-07-29","primaryCompletion":"2026-08-31","completion":"2026-08-31","firstPosted":"2024-04-23","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":9,"countries":["France","Germany","Spain","United Kingdom","United States"],"locations":[{"facility":"Nebraska Cancer Specialists","status":null,"city":"Omaha","state":"Nebraska","country":"United States","latitude":41.25626,"longitude":-95.94043},{"facility":"Memorial Sloan Kettering Cancer Ctr","status":null,"city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"Novartis Investigative Site","status":null,"city":"Nantes","state":null,"country":"France","latitude":47.21725,"longitude":-1.55336},{"facility":"Novartis Investigative Site","status":null,"city":"München","state":null,"country":"Germany","latitude":51.60698,"longitude":13.31243},{"facility":"Novartis Investigative Site","status":null,"city":"Rostock","state":null,"country":"Germany","latitude":54.0887,"longitude":12.14049},{"facility":"Novartis Investigative Site","status":null,"city":"L'Hospitalet de Llobregat","state":"Barcelona","country":"Spain","latitude":41.35967,"longitude":2.10028},{"facility":"Novartis Investigative Site","status":null,"city":"Madrid","state":null,"country":"Spain","latitude":40.4165,"longitude":-3.70256},{"facility":"Novartis Investigative Site","status":null,"city":"Sutton","state":"Surrey","country":"United Kingdom","latitude":51.35,"longitude":-0.2},{"facility":"Novartis Investigative Site","status":null,"city":"London","state":null,"country":"United Kingdom","latitude":51.50853,"longitude":-0.12574}],"eligibility":{"criteria":"Key Inclusion criteria:\n\n* Participants must have metastatic prostate cancer with neuroendocrine differentiation as determined by at least one of the following:\n\n  * Histologically small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy confirmed by local laboratory.\n  * Expression of NEPC markers (e.g., chromogranin or synaptophysin) in tumor tissue by IHC confirmed by local laboratory\n  * Progression of visceral metastases in the absence of PSA progression\n  * Serum chromogranin A \\> 5x normal limit, or neuron-specific enolase \\> 2x normal limit with control for proton-pump inhibitors (PPI) drugs among concomitant treatment\n  * Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)\n* PSMA and/or SSTR2 and/or GRPR PET-positive participants, with at least one measurable lesion per RECIST 1.1 with moderate target expression in at least one of the 3 PET/CT scans per BICR assessment\n* Castrate level of serum/plasma testosterone (\\< 50 ng/dl, or \\< 1.7 nmol/L) for participants with adenocarcinoma component or stable testosterone level for participants with pure neuroendocrine carcinoma\n* Recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapy\n* Participant has adequate bone marrow and organ function (as assessed by central laboratory for eligibility)\n* ECOG status =\\< 2\n\nKey Exclusion criteria:\n\n* Previous treatment with any of the following within 6 months prior to Screening: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation\n* Previous PSMA, SSTR2, or GRPR targeted radioligand therapy\n* Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy or investigational therapy\n* History of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity\n* Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression\n* History or current diagnosis of ECG abnormalities indicating significant risk of safety for study participants\n\nOther protocol-defined inclusion/exclusion criteria may apply.","minimumAge":"18 Years","maximumAge":"100 Years","sex":"MALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"[68Ga]Ga-PSMA-11","description":"\\[68Ga\\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)"},{"type":"DRUG","name":"[68Ga]GA-DOTA-TATE","description":"\\[68Ga\\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)"},{"type":"DRUG","name":"[68Ga]Ga-NeoB","description":"\\[68Ga\\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi)."},{"type":"DRUG","name":"[177Lu]Lu-PSMA-617","description":"\\[177Lu\\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for 6 cycles."},{"type":"DRUG","name":"[177Lu]Lu-DOTA-TATE","description":"\\[177Lu\\]Lu-DOTA-TATE will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%) every 6 weeks for 6 cycles."},{"type":"DRUG","name":"[177Lu]Lu-NeoB","description":"\\[177Lu\\]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq (250mCi) every 6 weeks for 6 cycles"},{"type":"DRUG","name":"L-Lysine HCl-L-Arginine HCl, 2.5 %,","description":"sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)"},{"type":"DRUG","name":"Gonadotropin-releasing hormone (GnRH) analogues","description":"Anatomical Therapeutic Chemical \\[ATC\\] code L02AE"},{"type":"DRUG","name":"GnRH antagonists","description":"abarelix, degarelix, or relugolix"},{"type":"DRUG","name":"Antiemetics & antinauseants","description":"ATC code A04A"},{"type":"DRUG","name":"Metoclopramide","description":"ATC code A03FA01"}],"primaryOutcomes":[{"measure":"Number/extent of lesions with at least a moderate uptake of any of the Radioligand Imaging (RLI)","description":"Number/extent of lesions with at least a moderate update of any of the RLIs according to visual assessment scoring scale on each corresponding targeted PET/CT scan based on blinded independent central review (BICR) assessment.","timeFrame":"Baseline (baseline imaging is performed during the 42 day screening period)"},{"measure":"Percentage changes in quantitative PET parameters.","description":"Percentage changes in quantitative PET/CT parameters (SUVmax, SUVmean, SUVpeak, target-positive Tumor Volume (target -TV), Total Lesion (target (TL-target)\\] and changes in number of target-positive lesions (as per visual assessment) on each corresponding target PET/CT based on BICR.","timeFrame":"Post-Baseline (from date of baseline imaging scans to post-baseline scans, at least 6 weeks after receiving the first cycle of radioligand treatment)"}],"secondaryOutcomes":[{"measure":"Overall Response Rate (ORR)","description":"Overall Response Rate (ORR) is defined as the proportion of participants with the best overall response (BOR) of confirmed complete response (CR) or partial response (PR) based on Prostate Cancer Working Group 3 (PCWG3) modified-RECIST v1.1.","timeFrame":"From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months"},{"measure":"Disease Control Rate (DCR)","description":"Disease Control Rate (DCR) is defined as the proportion of participants with BOR of CR, PR, stable disease (SD), or non-CR/non-PD based on PCWG3 modified-RECIST v1.1.","timeFrame":"From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months"},{"measure":"Duration of response (DOR)","description":"Duration of response (DOR) is defined as the time (in months) from the date of the first confirmed response (CR or PR) to the date of first documented progression according to PCWG3 modified-RECIST v1.1 or death due to any cause, among participants with a confirmed response.","timeFrame":"From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 31 months"},{"measure":"Radiographic Progression-free Survival (rPFS)","description":"Radiographic Progression-free Survival (rPFS) is defined as the time from the date of first dose of study treatment to the date of first documented radiographic progression (as assessed by the local investigator and using PCWG3 modified-RECIST v1.1 criteria) or death due to any cause.","timeFrame":"From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months"},{"measure":"Proportion of participants with a decline in PSA level","description":"The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit.","timeFrame":"Baseline, Cycle 1 Day 1 (each cycle is 42 days), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, End Of Treatment, 6 weeks after End of Treatment"},{"measure":"Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Therapy (RLT)","description":"The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Events (AEs) and Serious Adverse Events (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.\n\nAdverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit.\n\nParticipants receiving the study treatment \\[68Ga\\]Ga-DOTA-TATE/\\[177Lu\\]Lu-PSMA-617 or \\[177Lu\\]Lu-NeoB will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events.","timeFrame":"Up to 42 days after last dose administration (Safety Follow-up) and every 12 weeks until end of long term follow up (Long-term FU) for selected AEs and SAEs"},{"measure":"Dose modifications for [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB","description":"Dose modifications (dose interruptions, dose discontinuations and reductions) for \\[177Lu\\]Lu-PSMA-617, \\[177Lu\\]Lu-DOTA-TATE and \\[177Lu\\]Lu-NeoB will be assessed and summarized using descriptive statistics.","timeFrame":"Up to 42 days after last dose administration (Safety Follow-up)"},{"measure":"Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Imaging (RLI)","description":"The distribution of adverse events for Radioligand Imaging (RLI) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.","timeFrame":"Continuously from informed consent for the first 6 weeks and selected AEs and SAEs thereafter"},{"measure":"Blood radioactivity concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)","description":"Data will be listed by participant and visit/sampling time point. Descriptive summary statistics will be provided by visit/sampling time point and treatment arm including the frequency (n, %) of concentrations below the lower limit of quantification (LLOQ) and reported as zero.","timeFrame":"Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI."},{"measure":"Blood mass concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)","description":"Data will be listed by participant and visit/sampling time point. Descriptive summary statistics will be provided by visit/sampling time point and treatment arm including the frequency (n, %) of concentrations below the lower limit of quantification (LLOQ) and reported as zero.","timeFrame":"Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hr, 4 hr, 6 hrs, 24 hrs, 48 hrs 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI."}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06379217"},{"nctId":"NCT06502158","title":"Mifepristone vs Misoprostol","officialTitle":"Mifepristone Versus Misoprostol for Cervical Preparation Prior to Procedural Abortion at 12 to 16 Weeks' Gestation in an Academic Medical Center: a Randomized Controlled Pilot Trial","summary":"The Investigator team hypothesizes that in a randomized trial comparing mifepristone-alone or misoprostol-alone for cervical preparation for procedural abortions at 12 to 16 weeks in hospital-based care, the proportion of patients who achieve successful cervical dilation will be different between the study groups.","detailedDescription":"Cervical preparation is a critical component for the provision of safe abortion care in the later first trimester and beyond. The risk of surgical complications increases at 12 to 13 weeks gestation and routine use of cervical preparation is recommended. Cervical preparation options include misoprostol, mifepristone, and cervical dilators. Regimen choice is often guided by provider comfort, preference, or institutional guidelines. Misoprostol offers the advantage of facilitating same-day procedures, but side effects like pain and gastrointestinal symptoms can negatively affect patients' experiences. Furthermore, using misoprostol can pose logistical challenges in hospital-based main operating room environments, where abortions occur concurrently with all other surgical cases. Mifepristone is better tolerated than misoprostol but requires a multiple-day protocol for administration, which can pose logistical challenges.\n\nSeveral studies demonstrate mifepristone's efficacy and safety as a cervical ripening agent for up to 16 weeks' gestation, however, despite its effectiveness, mifepristone for cervical preparation before procedural abortion has previously been limited by availability and cost. Recent studies demonstrating mifepristone's adjunctive benefit with osmotic dilators later in pregnancy, however, have broadened its use.\n\nWhile most abortion care in the United States occurs in outpatient settings, about 3% occur in hospitals. This is expected to increase as the Dobbs versus Jackson Women's Health Organization decision exacerbates disparities in abortion access. In hospital-based abortion care, particularly at academic centers providing abortion training, there is a pressing need for innovative measures for cervical ripening. The Complex Family Planning Fellowship-trained faculty members at Montefiore will serve as research study surgeons. Cases will be performed in the main operating room under sedation or general anesthesia as determined by the anesthesiologist. A paracervical block of 20cc 1% lidocaine, with or without vasopressin, will be administered in accordance with standard practices.","peptideSlugs":["vasopressin"],"peptideNames":["Vasopressin"],"conditions":["Cervical Preparation"],"keywords":["Procedural Abortion","Surgical Abortion","Abortion, First Trimester","Cervical Dilators"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Montefiore Medical Center","slug":"montefiore-medical-center","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":94,"dates":{"start":"2024-10-31","primaryCompletion":"2027-06","completion":"2027-06","firstPosted":"2024-07-16","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Montefiore Medical Center","status":"RECRUITING","city":"The Bronx","state":"New York","country":"United States","latitude":40.84985,"longitude":-73.86641}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* English or Spanish-speaking\n* Capacity to consent\n* Seeking induced abortion of a singleton pregnancy between 12 weeks, 0 days and 16 weeks, 6 days (based on age at day of surgery)\n\nExclusion Criteria:\n\n* History of more than two prior Cesarean deliveries\n* Sonographic evidence of placenta previa\n* Sonographic concern for morbidly adherent placenta\n* Prior obstetric hemorrhage requiring transfusion\n* Obstructive cervical or lower uterine segment fibroid\n* Current therapeutic anticoagulation use\n* Cerclage in situ\n* History of more than one prior cervical excisional procedure\n* BMI greater than 50 kg/m\\^2","minimumAge":"18 Years","maximumAge":"45 Years","sex":"FEMALE","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Mifepristone","description":"200 milligrams (mg)"},{"type":"DRUG","name":"Misoprostol","description":"600 micrograms (ug)"}],"primaryOutcomes":[{"measure":"Percentage of participants achieving Intended dilation","description":"The proportion of participants achieving intended dilation at the start of the procedure will be summarized by treatment group and reported in percentages. Achievement of intended dilation will be determined by the attending surgeon. Overdilation resulting in passage of products of conception prior to time of surgery will be characterized as a treatment failure.","timeFrame":"At time of surgery"}],"secondaryOutcomes":[{"measure":"Cervical dilation at start of procedure","description":"Cervical dilation in centimeters (cm) at start of procedure will be summarized and reported using basic descriptive statistics.","timeFrame":"Start of the Procedure"},{"measure":"Surgical time","description":"Total surgical time will quantified and reported by treatment arm using basic descriptive statistics.","timeFrame":"Start to end of procedure, up to 4 hours"},{"measure":"Estimated blood loss","description":"Estimated blood loss will be quantified and reported per treatment arm using basic descriptive statistics.","timeFrame":"Start to end of procedure, up to 4 hours"},{"measure":"Presence of Intraoperative Complications","description":"The presence of peri-operative complications, defined as instances of hemorrhage, use of uterotonic medications, passage of products of conception prior to time of surgery, instances of extramural delivery, or need for unscheduled procedures, will be summarized and reported as \"Yes\" or \"No\" using basic descriptive statistics.","timeFrame":"From preoperative visit to discharge, up to 2 days"},{"measure":"Patient Satisfaction","description":"Patient Satisfaction will be assessed by responses to a survey administered in the Postoperative Care Unit (PACU) following the procedure. The patient will be asked to rate their satisfaction with the procedure on a 6-point Likert scale ranging from 0 (Not at all satisfied) to 5 (Most satisfied). Responses will be summarized by treatment group using basic descriptive statistics. Increased scores are associated with increased satisfaction.","timeFrame":"From preoperative visit to discharge, up to 2 days"},{"measure":"Provider Satisfaction","description":"Provider Satisfaction will be assessed by responses to a survey administered following the procedure. The care provider will be asked to rate their satisfaction with the procedure on a 6-point Likert scale ranging from 0 (Not at all satisfied) to 5 (Most satisfied). Responses will be summarized by treatment group using basic descriptive statistics. Increased scores are associated with increased satisfaction.","timeFrame":"From preoperative visit to discharge, up to 2 days"}],"publications":[{"pmid":"26683499","citation":"Allen RH, Goldberg AB. Cervical dilation before first-trimester surgical abortion (<14 weeks' gestation). Contraception. 2016 Apr;93(4):277-291. doi: 10.1016/j.contraception.2015.12.001. Epub 2015 Dec 9."},{"pmid":"20166091","citation":"Kapp N, Lohr PA, Ngo TD, Hayes JL. Cervical preparation for first trimester surgical abortion. Cochrane Database Syst Rev. 2010 Feb 17;2010(2):CD007207. doi: 10.1002/14651858.CD007207.pub2."},{"pmid":"24331860","citation":"Fox MC, Krajewski CM. Cervical preparation for second-trimester surgical abortion prior to 20 weeks' gestation: SFP Guideline #2013-4. Contraception. 2014 Feb;89(2):75-84. doi: 10.1016/j.contraception.2013.11.001. Epub 2013 Nov 11."},{"pmid":"11035353","citation":"Ashok PW, Flett GM, Templeton A. Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study. Am J Obstet Gynecol. 2000 Oct;183(4):998-1002. doi: 10.1067/mob.2000.106767."},{"pmid":"22682721","citation":"Borgatta L, Roncari D, Sonalkar S, Mark A, Hou MY, Finneseth M, Vragovic O. Mifepristone vs. osmotic dilator insertion for cervical preparation prior to surgical abortion at 14-16 weeks: a randomized trial. Contraception. 2012 Nov;86(5):567-71. doi: 10.1016/j.contraception.2012.05.002. Epub 2012 Jun 6."},{"pmid":"27132200","citation":"Ohannessian A, Baumstarck K, Maruani J, Cohen-Solal E, Auquier P, Agostini A. Mifepristone and misoprostol for cervical ripening in surgical abortion between 12 and 14 weeks of gestation: a randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2016 Jun;201:151-5. doi: 10.1016/j.ejogrb.2016.04.007. Epub 2016 Apr 11."},{"pmid":"32007418","citation":"Diedrich JT, Drey EA, Newmann SJ. Society of Family Planning clinical recommendations: Cervical preparation for dilation and evacuation at 20-24 weeks' gestation. Contraception. 2020 May;101(5):286-292. doi: 10.1016/j.contraception.2020.01.002. Epub 2020 Jan 31."},{"pmid":"36404279","citation":"Jones RK, Kirstein M, Philbin J. Abortion incidence and service availability in the United States, 2020. Perspect Sex Reprod Health. 2022 Dec;54(4):128-141. doi: 10.1363/psrh.12215. Epub 2022 Nov 20."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06502158"},{"nctId":"NCT06930625","title":"A Study to Assess the Efficacy and Safety of Debio 4126 in Participants With Acromegaly Previously Treated With Somatostatin Analogs","officialTitle":"A Phase 3 Randomized 3-arm Trial (Double-blind Debio 4126, Placebo Control, and Open-label Debio 4126), to Assess the Efficacy and Safety of Debio 4126, a 12-week Octreotide Formulation, in Patients With Acromegaly Previously Treated With Somatostatin Analogs","summary":"The primary purpose of this study is to assess the effect of Debio 4126 in the maintenance of the levels of insulin-like growth factor 1 (IGF-1) ≤1x upper limit of normal (ULN) in the double-blind period (Period 1) in comparison to placebo at week 36.","detailedDescription":null,"peptideSlugs":["octreotide"],"peptideNames":["Octreotide"],"conditions":["Acromegaly"],"keywords":["IGF-1","Growth hormone","Pituitary gland","Gigantism"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Debiopharm International SA","slug":"debiopharm-international-sa","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":119,"dates":{"start":"2025-11-26","primaryCompletion":"2028-06","completion":"2029-03","firstPosted":"2025-04-16","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":72,"countries":["Austria","Belgium","Brazil","Bulgaria","Denmark","Estonia","France","Germany","Hungary","Israel","Italy","Latvia","Lithuania","Poland","Romania","Serbia","Slovakia","Spain","Sweden","United Kingdom","United States"],"locations":[{"facility":"Cedars Sinai Medical Center","status":"RECRUITING","city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Northwestern University","status":"RECRUITING","city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Harvard Medical School","status":"RECRUITING","city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977},{"facility":"Washington University-School of Medicine","status":"RECRUITING","city":"St Louis","state":"Missouri","country":"United States","latitude":38.62727,"longitude":-90.19789},{"facility":"Palm Research Center Inc","status":"RECRUITING","city":"Las Vegas","state":"Nevada","country":"United States","latitude":36.17497,"longitude":-115.13722},{"facility":"NYU Grossman School of Medicine","status":"NOT_YET_RECRUITING","city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597},{"facility":"The Cleveland Clinic","status":"RECRUITING","city":"Cleveland","state":"Ohio","country":"United States","latitude":41.4995,"longitude":-81.69541},{"facility":"The Ohio State University","status":"RECRUITING","city":"Columbus","state":"Ohio","country":"United States","latitude":39.96118,"longitude":-82.99879},{"facility":"Oregon Health & Science University","status":"RECRUITING","city":"Portland","state":"Oregon","country":"United States","latitude":45.52345,"longitude":-122.67621},{"facility":"Thomas Jefferson University","status":"RECRUITING","city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"Medical University Graz","status":"RECRUITING","city":"Graz","state":null,"country":"Austria","latitude":47.06733,"longitude":15.44197},{"facility":"Medizinische Universitaet Wien - Division of Endocrinology and Metabolism","status":"RECRUITING","city":"Vienna","state":null,"country":"Austria","latitude":48.20849,"longitude":16.37208},{"facility":"UZ Gent","status":"RECRUITING","city":"Ghent","state":null,"country":"Belgium","latitude":51.05,"longitude":3.71667},{"facility":"CETI - Centro de Estudos em Terapias Inovadoras","status":"RECRUITING","city":"Curitiba","state":null,"country":"Brazil","latitude":-25.42778,"longitude":-49.27306},{"facility":"Nucleo de Pesquisa e Desenvolvimento de Medicamentos (NPDM)","status":"RECRUITING","city":"Fortaleza","state":null,"country":"Brazil","latitude":-3.71722,"longitude":-38.54306},{"facility":"Hospital das Clinicas da UFMG","status":"RECRUITING","city":"Minas Gerais","state":null,"country":"Brazil","latitude":-8.96667,"longitude":-72.78333},{"facility":"Instituto Estadual do Cérebro Paulo Niemeyer (IECPN)","status":"RECRUITING","city":"Rio de Janeiro","state":null,"country":"Brazil","latitude":-22.90642,"longitude":-43.18223},{"facility":"Hospital das Clinicas - University of Sao Paulo Medical School","status":"RECRUITING","city":"São Paulo","state":null,"country":"Brazil","latitude":-23.5475,"longitude":-46.63611},{"facility":"University Specialized Hospital for Active Treatment of Endocrinology Akad. lv Penchev EAD","status":"RECRUITING","city":"Sofia","state":null,"country":"Bulgaria","latitude":42.69751,"longitude":23.32415},{"facility":"Rigshospitalet, Blegdamsvej 9","status":"RECRUITING","city":"Copenhagen","state":null,"country":"Denmark","latitude":55.67594,"longitude":12.56553},{"facility":"Zealand University Hospital","status":"RECRUITING","city":"Køge","state":null,"country":"Denmark","latitude":55.45802,"longitude":12.18214},{"facility":"East Tallinn Central Hospital","status":"RECRUITING","city":"Tallinn","state":null,"country":"Estonia","latitude":59.43696,"longitude":24.75353},{"facility":"North Estonia Medical Centre Foundation","status":"RECRUITING","city":"Tallinn","state":null,"country":"Estonia","latitude":59.43696,"longitude":24.75353},{"facility":"CHU d'Angers","status":"RECRUITING","city":"Angers","state":null,"country":"France","latitude":47.47156,"longitude":-0.55202}],"eligibility":{"criteria":"Inclusion criteria\n\n1. Patients ≥18 years of age\n2. Patients who are receiving octreotide or lanreotide monotherapy for acromegaly for at least 6 months, at a stable dose for the last 12 weeks.\n3. IGF-1 at screening ≤1x ULN\n4. Acromegaly diagnosis, defined as per protocol\n5. Adequate bone marrow, hepatic and renal function\n6. To enter Period 2 (Arms A and B): IGF-1 ≤1x ULN at Week 34, or up to Week 48 when treated with rescue medication\n7. Other protocol-defined criteria apply\n\nExclusion criteria\n\n1. Compression of optic chiasm causing visual defects\n2. Symptomatic cholelithiasis or bile duct dilatation\n3. Planned cholecystectomy during the trial duration\n4. Acute or chronic pancreatitis\n5. Pituitary radiotherapy\n6. Uncontrolled hypothyroidism\n7. Uncontrolled diabetes\n8. Pituitary surgery within 6 months before screening or planned on trial\n9. Treatment with pasireotide within 6 months prior to screening, pegvisomant or dopamine agonists within 3 months prior to screening\n10. Recent or ongoing cardiovascular or thromboembolic diseases including heart failure, myocardial infarction, stroke, certain arrythmias, pulmonary embolism\n11. Other protocol-defined criteria apply","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Debio 4126","description":"IM injection, a 12-week extended-release formulation of octreotide"},{"type":"DRUG","name":"Placebo","description":"IM injection of mannitol suspension"}],"primaryOutcomes":[{"measure":"Double-blind Period: Percentage of Participants With IGF-1 ≤1x ULN","description":null,"timeFrame":"36 Weeks"}],"secondaryOutcomes":[{"measure":"Arm C: Percentage of Participants With IGF-1 ≤1x ULN","description":null,"timeFrame":"36 Weeks"},{"measure":"Percent Change From Baseline in IGF-1 Values","description":null,"timeFrame":"Up to 108 Weeks"},{"measure":"Percentage of Participants With IGF-1 ≤1x ULN","description":null,"timeFrame":"Up to 108 Weeks"},{"measure":"Percentage of Participants With Growth Hormone (GH) Level <1 ng/mL","description":null,"timeFrame":"Up to 108 Weeks"},{"measure":"Double-blind Period: Percentage of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)","description":null,"timeFrame":"Up to 36 Weeks"},{"measure":"Percentage of Participants Who Experienced at Least One TEAE","description":null,"timeFrame":"Up to 113 Weeks"},{"measure":"Local Tolerability of Debio 4126 as Assessed by Erythema, Swelling, and Induration at the Injection Site Using Investigator Assessment","description":null,"timeFrame":"Up to 108 Weeks"},{"measure":"Local Tolerability of Debio 4126 as Assessed by Pain at Injection Site Based on Pain Visual Analog Scale (VAS) Score","description":null,"timeFrame":"Up to 108 Weeks"},{"measure":"Double-blind Period: Percentage of Participants Taking Rescue Medication","description":null,"timeFrame":"Up to 36 Weeks"},{"measure":"Trough Plasma Concentration (Ctrough) of Debio 4126","description":null,"timeFrame":"Up to 96 Weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06930625"},{"nctId":"NCT07011667","title":"A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term","officialTitle":"Efficacy and Safety of Cagrilintide s.c. in Combination With Semaglutide s.c. (CagriSema s.c.) Once Weekly for Weight Management and Long-term Weight Maintenance in Participants With Obesity","summary":"This study will look at how well CagriSema helps people living with obesity to lose weight and maintain the weight loss long-term. The study has 2 parts: The first part is called 'the main study' and the second part is called 'the extension study'. In the main study participants will either get CagriSema (a study medicine) or placebo (a dummy medicine that looks like CagriSema but has no active ingredient). Which treatment participants get is decided by chance. Participants are two times more likely to get CagriSema than placebo. If participants get CagriSema in the main study, participants will continue on CagriSema in the extension study. Which dose of CagriSema participants will continue on is decided by chance. If participants get placebo in the main study, participants will get CagriSema in the extension study. Participants will take one injection of study medicine once a week. The study will last for about 3 years and 3 months.","detailedDescription":null,"peptideSlugs":["semaglutide","cagrilintide"],"peptideNames":["Semaglutide","Cagrilintide"],"conditions":["Obesity"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Novo Nordisk","slug":"novo-nordisk","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":609,"dates":{"start":"2025-06-03","primaryCompletion":"2027-03-01","completion":"2028-10-17","firstPosted":"2025-06-09","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":46,"countries":["United States"],"locations":[{"facility":"FDRC","status":null,"city":"Costa Mesa","state":"California","country":"United States","latitude":33.64113,"longitude":-117.91867},{"facility":"Linda Vista Health Care Ctr","status":null,"city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Diablo Clinical Research, Inc.","status":null,"city":"Walnut Creek","state":"California","country":"United States","latitude":37.90631,"longitude":-122.06496},{"facility":"Northeast Research Institute","status":null,"city":"Fleming Island","state":"Florida","country":"United States","latitude":30.0933,"longitude":-81.71898},{"facility":"Jacksonville Ctr For Clin Res","status":null,"city":"Jacksonville","state":"Florida","country":"United States","latitude":30.33218,"longitude":-81.65565},{"facility":"South Broward Research LLC","status":null,"city":"Miramar","state":"Florida","country":"United States","latitude":25.98731,"longitude":-80.23227},{"facility":"Florida Inst For Clin Res LLC","status":null,"city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Oviedo Medical Research, LLC","status":null,"city":"Oviedo","state":"Florida","country":"United States","latitude":28.67,"longitude":-81.20812},{"facility":"Center for Diab,Obes & Metab","status":null,"city":"Pembroke Pines","state":"Florida","country":"United States","latitude":26.00315,"longitude":-80.22394},{"facility":"Hope Clin Res & Wellness","status":null,"city":"Conyers","state":"Georgia","country":"United States","latitude":33.66761,"longitude":-84.01769},{"facility":"Endocrine Research Solutions","status":null,"city":"Roswell","state":"Georgia","country":"United States","latitude":34.02316,"longitude":-84.36159},{"facility":"Great Lakes Clinical Trials","status":null,"city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Endeavor Health","status":null,"city":"Skokie","state":"Illinois","country":"United States","latitude":42.03336,"longitude":-87.73339},{"facility":"Evanston Premier Hlthcr Res","status":null,"city":"Skokie","state":"Illinois","country":"United States","latitude":42.03336,"longitude":-87.73339},{"facility":"Midwest Inst For Clin Res","status":null,"city":"Indianapolis","state":"Indiana","country":"United States","latitude":39.76838,"longitude":-86.15804},{"facility":"Iowa Diab & Endo Res Center","status":null,"city":"West Des Moines","state":"Iowa","country":"United States","latitude":41.57721,"longitude":-93.71133},{"facility":"Northern Pines Hlth Ctr, PC","status":null,"city":"Buckley","state":"Michigan","country":"United States","latitude":44.50445,"longitude":-85.67701},{"facility":"StudyMetrix Research LLC","status":null,"city":"City of Saint Peters","state":"Missouri","country":"United States","latitude":38.80033,"longitude":-90.62651},{"facility":"Amicis Centers of Clinical Research","status":null,"city":"St Louis","state":"Missouri","country":"United States","latitude":38.62727,"longitude":-90.19789},{"facility":"Mercury Str Med Grp, PLLC","status":null,"city":"Butte","state":"Montana","country":"United States","latitude":46.00382,"longitude":-112.53474},{"facility":"Southgate Medical Group, LLP","status":null,"city":"West Seneca","state":"New York","country":"United States","latitude":42.85006,"longitude":-78.79975},{"facility":"Great Lakes Medical Research","status":null,"city":"Westfield","state":"New York","country":"United States","latitude":42.32228,"longitude":-79.5781},{"facility":"University of North Carolina","status":null,"city":"Chapel Hill","state":"North Carolina","country":"United States","latitude":35.9132,"longitude":-79.05584},{"facility":"Medication Mgmnt, LLC_Grnsboro","status":null,"city":"Greensboro","state":"North Carolina","country":"United States","latitude":36.07264,"longitude":-79.79198}],"eligibility":{"criteria":"key Inclusion Criteria:\n\n* Male or female (sex at birth).\n* Age 18 years or above at the time of signing the informed consent.\n* BMI ≥ 30.0 kilogram per square meter (kg/m\\^2) at screening.\n* Participant has a wish to lose at least 25% of body weight within 80 weeks from randomisation.\n\nkey Exclusion Criteria:\n\n* Glycated haemoglobin (HbA1c) ≥ 6.5% (48 millimole per mole \\[mmol/mol\\]) as measured by the central laboratory at screening.\n* History of type 1 or type 2 diabetes.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"CagriSema (Cagrilintide B and Semaglutide I)","description":"CagriSema (Cagrilintide B and Semaglutide I) will be administered subcutaneously using DV3384 pen-injector."},{"type":"DRUG","name":"Placebo matched to CagriSema (Cagrilintide B and Semaglutide I)","description":"Placebo matched to Cagrilintide B and placebo matched to Semaglutide I will be administered subcutaneously using DV3384 pen-injector."}],"primaryOutcomes":[{"measure":"Relative change in body weight","description":"Measured as percentage change.","timeFrame":"From baseline (week 0) to week 80"}],"secondaryOutcomes":[{"measure":"Relative change in body weight in women","description":"Measured as percentage change.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Number of participants who achieve greater than or equals (≥) 20% weight reduction","description":"Measured as count of participants.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Number of participants who achieve ≥ 25% weight reduction","description":"Measured as count of participants.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Number of participants who achieve ≥ 30% weight reduction","description":"Measured as count of participants.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Number of participants who achieve BMI < 30 kg/m^2","description":"Measured as count of participants.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Number of participants who achieve normal body mass index (BMI) (18.5 kilograms per meter square (kg/m^2) less than or equal to (≤ ) BMI < 25 kg/m^2)","description":"Measured as count of participants.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Change in waist circumference","description":"Measured as centimeter (cm).","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Change in systolic blood pressure","description":"Measured as millimeters of mercury (mmHg).","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Ratio to baseline in C-reactive protein (CRP)","description":"Measured as ratio.","timeFrame":"From baseline (week 0) to week 80"},{"measure":"Ratio to baseline in lipids: non-high density lipoprotein (HDL) cholesterol","description":"Measured as ratio.","timeFrame":"From baseline (week 0) to week 80"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07011667"},{"nctId":"NCT07037433","title":"Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity","officialTitle":"A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity","summary":"The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.","detailedDescription":null,"peptideSlugs":["maridebart-cafraglutide"],"peptideNames":["Maridebart cafraglutide"],"conditions":["Atherosclerotic Cardiovascular Disease","Overweight","Obesity"],"keywords":["Atherosclerotic Cardiovascular Disease","Overweight","Obesity","Maridebart cafraglutide","AMG 133","MariTide"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Amgen","slug":"amgen","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":12800,"dates":{"start":"2025-07-25","primaryCompletion":"2028-06-30","completion":"2030-09-29","firstPosted":"2025-06-25","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":782,"countries":["Argentina","Australia","Austria","Belgium","Brazil","Bulgaria","Canada","Chile","China","Colombia","Czechia","Denmark","Finland","France","Germany","Greece","Hong Kong","Hungary","Italy","Japan","Mexico","Netherlands","Poland","Portugal","Puerto Rico","Romania","Singapore","Slovakia","South Korea","Spain","Sweden","Switzerland","Taiwan","Turkey (Türkiye)","United Kingdom","United States"],"locations":[{"facility":"Alliance For Multispecialty Research - Daphne","status":"RECRUITING","city":"Daphne","state":"Alabama","country":"United States","latitude":30.60353,"longitude":-87.9036},{"facility":"Eastern Shore Research Institute","status":"RECRUITING","city":"Fairhope","state":"Alabama","country":"United States","latitude":30.52297,"longitude":-87.90333},{"facility":"Heart Center Research LLC","status":"RECRUITING","city":"Huntsville","state":"Alabama","country":"United States","latitude":34.7304,"longitude":-86.58594},{"facility":"Mobile Heart Specialists PC","status":"RECRUITING","city":"Mobile","state":"Alabama","country":"United States","latitude":30.69436,"longitude":-88.04305},{"facility":"Syed Research Consultants LLC","status":"RECRUITING","city":"Sheffield","state":"Alabama","country":"United States","latitude":34.76509,"longitude":-87.69864},{"facility":"Synexus Clinical Research US, Inc.","status":"RECRUITING","city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Medical Advancement Centers of Arizona","status":"RECRUITING","city":"Phoenix","state":"Arizona","country":"United States","latitude":33.44838,"longitude":-112.07404},{"facility":"Valley Clinical Trials, LLC dba Flourish Research","status":"RECRUITING","city":"Covina","state":"California","country":"United States","latitude":34.09001,"longitude":-117.89034},{"facility":"Velocity Clinical Research- Huntington Park","status":"RECRUITING","city":"Huntington Park","state":"California","country":"United States","latitude":33.98168,"longitude":-118.22507},{"facility":"Velocity Clinical Research- Los Angeles","status":"COMPLETED","city":"La Mesa","state":"California","country":"United States","latitude":32.76783,"longitude":-117.02308},{"facility":"Orange County Research Center","status":"RECRUITING","city":"Lake Forest","state":"California","country":"United States","latitude":33.64697,"longitude":-117.68922},{"facility":"Biopharma Informatic - The Cardiovascular Center","status":"RECRUITING","city":"Redding","state":"California","country":"United States","latitude":40.58654,"longitude":-122.39168},{"facility":"Acclaim Clinical Research","status":"RECRUITING","city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Encompass Clinical Research","status":"RECRUITING","city":"Spring Valley","state":"California","country":"United States","latitude":32.74477,"longitude":-116.99892},{"facility":"Diablo Clinical Research","status":"RECRUITING","city":"Walnut Creek","state":"California","country":"United States","latitude":37.90631,"longitude":-122.06496},{"facility":"Focus Clinical Research","status":"RECRUITING","city":"West Hills","state":"California","country":"United States","latitude":34.19731,"longitude":-118.64398},{"facility":"Family Practice Associates","status":"RECRUITING","city":"Wilmington","state":"Delaware","country":"United States","latitude":39.74595,"longitude":-75.54659},{"facility":"Excel Medical Clinical Trials","status":"RECRUITING","city":"Boca Raton","state":"Florida","country":"United States","latitude":26.35869,"longitude":-80.0831},{"facility":"Velocity Clinical Research - New Smyrna Beach","status":"RECRUITING","city":"Edgewater","state":"Florida","country":"United States","latitude":28.98888,"longitude":-80.90228},{"facility":"Alliance for Multispecialty Research - Fort Myers","status":"RECRUITING","city":"Fort Myers","state":"Florida","country":"United States","latitude":26.62168,"longitude":-81.84059},{"facility":"Elite Cardiac Research Center LLC","status":"RECRUITING","city":"Hialeah","state":"Florida","country":"United States","latitude":25.8576,"longitude":-80.27811},{"facility":"Elite Clinical Research","status":"RECRUITING","city":"Hialeah","state":"Florida","country":"United States","latitude":25.8576,"longitude":-80.27811},{"facility":"Zenith Clinical Research","status":"RECRUITING","city":"Hollywood","state":"Florida","country":"United States","latitude":26.0112,"longitude":-80.14949},{"facility":"Encore Medical Research LLC","status":"RECRUITING","city":"Hollywood","state":"Florida","country":"United States","latitude":26.0112,"longitude":-80.14949}],"eligibility":{"criteria":"Inclusion Criteria\n\n* Age ≥ 45 years at screening.\n* BMI of ≥ 27.0 kg/m\\^2 at screening.\n* History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:\n\n  * Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).\n  * Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).\n  * Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \\< 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.\n\nExclusion Criteria\n\n* History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).\n* New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.\n* Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.\n* For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):\n\n  * HbA1c \\> 10.0% (86 mmol/mol) at screening.\n  * History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.\n  * One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.\n  * History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.\n* Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.\n* History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.\n* Family (first-degree relative\\[s\\]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).\n* Calcitonin ≥ 50 ng/L (pg/mL) at screening.\n* Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) \\> 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) \\> 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).\n* History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).\n* Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.","minimumAge":"45 Years","maximumAge":"99 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Maridebart Cafraglutide","description":"Maridebart cafraglutide will be administered SC."},{"type":"DRUG","name":"Placebo","description":"Placebo will be administered SC."}],"primaryOutcomes":[{"measure":"Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE])","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, MI, Ischemic Stroke, Coronary Revascularization, or Heart Failure (HF) Event (5-point MACE)","description":null,"timeFrame":"Up to approximately 35 months"}],"secondaryOutcomes":[{"measure":"Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or HF Event","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke or Coronary Revascularization","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First MI","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First Ischemic Stroke","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to CV Death","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to All-cause Death","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First Coronary Revascularization","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First HF Event","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First HF Event or CV Death","description":null,"timeFrame":"Up to approximately 35 months"},{"measure":"Time to First Unstable Angina Requiring Hospitalization","description":null,"timeFrame":"Up to approximately 35 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07037433"},{"nctId":"NCT07154719","title":"GLP-1R Actions on Muscle and the Skeleton","officialTitle":"GLP-1R Actions on Muscle and the Skeleton","summary":"The GRAMS study objectives are to assess the musculoskeletal changes that occur after weight loss using GLP-1 based therapy. A lifestyle intervention with diet and exercise is included to assess any mitigating effects are provided, versus a control group with regular exercise and diet.","detailedDescription":"Obesity and type 2 diabetes remain at epidemic proportions in our country particularly in vulnerable populations such as elderly, and minority patients. Over the last 20 years, the use of incretin-based agents (Glucagon-like Peptide 1 Receptor Agonist (GLP-1 RA) and Glucose dependent insulinotrophic polypeptide (GIP) to treat these disorders has offered unprecedented advances based on significant weight loss and reduction in major cardiovascular endpoints. Whilst weight loss provides a vital aspect for addressing obesity and type 2 diabetes, there are concerns associated with the quality of weight reduction.\n\nThe impact of losing weight on the musculoskeletal system has garnered recent attention in the lay press. Reported high-impact studies have reported excessive loss of skeletal muscle using GLP-1 RAs. The data regarding combined therapies (GLP-1 RA and GIP) suggested smaller loses. This preliminary data is based on using a surrogate marker (fat-free mass) determined by dual energy x-ray absorptiometry (DXA).\n\nRecent reviews evaluating the impact that incretin-based agents have on fat-free-mass were found to be inconclusive based on high variability and multiple confounding factors. Assessing the impact that these agents have on the musculoskeletal system is now an important endeavor. (Aim 1-2) Diet-induced weight loss is also associated with bone loss, although little attention has focused on this potentially problematic outcome. In the CALERIE study, modest caloric restriction (15%) over two years led to weight loss and a 2% reduction in hip bone mineral density (BMD) among normal weight individuals. The mechanisms of weight loss-induced bone loss are unclear, although a drop in fat-free mass (which is composed of skeletal muscle, organs, water and connective tissues) principally muscle, such as occurs with the GLP1RAs, may predispose to injury, disability and bone loss. Another possibility is a mechanical form of skeletal adaptation to lower lean mass, through myokine mediated bone remodeling. However, significant trabecular bone loss in a non-weight bearing skeletal site occurs in mice as the investigators have shown in the mandible, from a 30% CR diet (Liu, personal communication). As such gravitational unloading due to weight loss is not solely responsible for deleterious skeletal changes. Despite the dramatic weight and lean mass loss from the GLP1 RAs, few clinical trials have focused on loss of muscle mass and fewer on any skeletal changes. In those that did, the results suggest equipoise for skeletal changes. There are no data on the skeletal effects from tirzepatide which can drive up to 25% weight loss. (Aim 1c) Also, it is unknown whether the addition of dietary modifications and resistance-based exercises impacts skeletal adaptation, muscle mass and bone loss. (Aim 2) Furthermore, there are inconsistent data in non-Hispanic Blacks with the GLP1 RAs because trial participation in under-represented populations has been poor. Hence, there is a major knowledge gap in our understanding the impact that a mixed GIP and GLP1RA, tirzepatide affects muscle and bone mass, particularly among underserved populations.\n\nThe wide-spread usage of GLP-1 related agents has not required formal recommendations regarding the use of exercises, specifically resistance-based exercises, or dietary protein optimization to address the potential for loss of fat-free mass or bone mineral density that has been suggested in studies evaluating body composition and bone density in subjects using these compounds. While the data for using such lifestyle interventions with diet and bariatric surgery have confirmed benefits in reducing loss of fat-free mass, the investigators know of only 1 published report using GLP-1 agents and exercise: Lundgren et al. found that in subjects using additional resistance-based exercise had a more favorable impact on sparing fat-free mass.\n\nAdditional gaps in our understanding remain despite the growing use and popularity of these agents. Additionally, patients with obesity and type 2 diabetes tend to develop ectopic fat within muscle (myosteatosis) that is not measured as part of fat free mass by DXA. It is posited that the major depot for acute loss of skeletal muscle from rapid weight loss may be from this portion of poor-quality lipid-rich tissue quelling major concerns. (Aim 2b) Aim 3, an explorative outcome, the investigators will determine if tirzepatide causes bone loss by measuring bone formation (P1NP) and bone resorption markers (NTx), if imbalanced skeletal remodeling is related to the change in total lean mass, muscle mass through reduced myokine (i.e., irisin) release, skeletal adaptation to weight change or another endocrine mechanism. Using a team science approach, the investigators will combine the expertise in metabolism and body composition of the PBRC group with skeletal expertise from MaineHealth to provide key insights into musculoskeletal effects from tirzepatide, a relatively new but often sought after drug for weight loss and type 2 diabetes. This supplement could also shed light on newer mechanisms of weight loss-induced bone loss and set the stage for a larger clinical trial.","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Musculoskeletal Abnormalities","Obesity","Sarcopenic Obesity","Osteoporosis","Drug Effect"],"keywords":["GLP-1 agonists","Obesity treatments","Muscleskeletal loss","Tirzepatide"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Pennington Biomedical Research Center","slug":"pennington-biomedical-research-center","class":"OTHER"},"collaborators":[{"name":"National Institutes of Health (NIH)","slug":"national-institutes-of-health-nih","class":"NIH"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":50,"dates":{"start":"2025-10-09","primaryCompletion":"2027-02-01","completion":"2027-05-01","firstPosted":"2025-09-04","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"Pennington Biomedical Research Center","status":null,"city":"Baton Rouge","state":"Louisiana","country":"United States","latitude":30.44332,"longitude":-91.18747},{"facility":"MaineHealth Center for Clinical and Translational Science","status":null,"city":"Scarborough","state":"Maine","country":"United States","latitude":43.57814,"longitude":-70.32172}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Subjects will have a BMI between 30kg/m2\n\n  * 40kg/m2 (inclusive)\n* Be between 18 and 50 years of age (inclusive).\n* Non-Hispanic Black males and females will be enrolled at PBRC.\n* Rural males and females will be enrolled at MaineHealth.\n* Female subjects will be premenopausal.\n* Females have had their last menstrual period less than 60 days before screening.\n* Females have the absence of menopausal-associated vasomotor symptoms.\n* All subjects must be able to use Lifestyle Toolkit as prescribed for intervention arm.\n\nExclusion Criteria:\n\n\\- Males and females over the age of 50 years of age\n\n* Menopausal females.\n* Subjects on systemic corticosteroids or other agents known to increase loss of muscle and bone mass.\n* Subjects who are on medications that increase or decrease weight status.\n* Subjects having contraindications to tirzepatide in the package insert.\n* Subjects with a history of malignancy other than non-melanoma skin cancer\n* Subjects with known osteoporosis or are on osteoporosis therapies (gonadal hormones or hormone antagonists).\n* Subjects with uncontrolled thyroid or parathyroid disease that may influence the study results.\n* Subjects with a clinically significant hematologic abnormality, kidney disease, liver disease, or diabetes.\n* Females of childbearing potential who do not agree to using an effective method of contraception during the study. Medically acceptable methods include oral contraceptive medication, an intrauterine device (IUD), an implantable contraceptive (such as Implanon), or a barrier method (such as condom or diaphragm with spermicide).\n\nInjectable contraceptives such as Depo-Provera are a cause for exclusion in that they can cause bone loss.\n\nAbstinence is acceptable, as is sexual activity exclusively with same sex partners.\n\nFertility Appreciation Based Methods (natural family planning) are also acceptable forms of addressing childbearing potential in all subjects. A urine pregnancy test (UPT) will be performed on all females of childbearing potential at the screening visit, 3 and 6 months.\n\n* Unable to follow Lifestyle Toolkit as prescribed for intervention arm.\n* Patient Health Questionnaire-9 (PHQ-9) Score equal to or greater than 15 (clinical depression).\n* Adults who are unable to consent.\n* Individuals who are not yet adults (infants, children and teenagers).\n* Pregnant females.\n* Incarcerated individuals.\n* Contraindication to MRI - including but not limited to non-removable metallic or electronic implants, claustrophobia or other fear of confinement, inability to tolerate loud scanner noise, body weight greater than 500 pounds.\n* Subjects with a baseline level of 25-OH vitamin D \\<15 ng/ml will be excluded from the trial. The subject's physician will be notified, and the subject will be referred to their primary care physician.\n* Any significant EKG abnormalities that are considered a risk for utilizing weight management therapies.","minimumAge":"18 Years","maximumAge":"50 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"GLP-1 based treatment for obesity"},{"type":"BEHAVIORAL","name":"Lifestyle toolkit","description":"2 ABBOTT protein shakes daily and resistance-based exercise x 3 days per week."}],"primaryOutcomes":[{"measure":"Changes in fat free mass (FFM) using DXA imaging. FFM equals all body composition that is not fat mass. This includes bone, skeletal muscle, organs, water and all connective tissues. The unit of measurement is in kilograms (kg) at baseline, 3 and 6 mo.","description":"DXA (Dual energy Xray absorptiometry)","timeFrame":"Baseline and time 3, and 6 months."}],"secondaryOutcomes":[{"measure":"MRI (thigh) without contrast","description":"To assess for muscle quality (% of skeletal muscle to intermuscular fat)","timeFrame":"Month 1 (baseline), month 3, month 6 (final visit)"},{"measure":"Osteocalcin","description":"Blood draw, metabolism biomarker","timeFrame":"Month 1 (baseline), month 3, month 6 (final visit)"},{"measure":"Irisin","description":"Blood draw, bone health biomarker","timeFrame":"Month 1 (baseline), month 3, month 6 (final visit)"},{"measure":"Procollagen 1 N-terminal peptide (P1NP)","description":"Blood draw, bone health biomarker","timeFrame":"Month 1 (baseline), month 3, and month 6 (final visit)"},{"measure":"C-Terminal Telopeptide of type I collagen (CTX-1)","description":"Blood draw, bone health biomarker","timeFrame":"Month 1 (baseline), month 3, month 6 (final visit)"},{"measure":"Insulin-like Growth Factor 1 (IGF-1)","description":"Blood draw, bone health biomarker","timeFrame":"Month 1 (baseline), month 3, month 6 (final visit)"}],"publications":[{"pmid":"10778870","citation":"Goodpaster BH, Theriault R, Watkins SC, Kelley DE. Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism. 2000 Apr;49(4):467-72. doi: 10.1016/s0026-0495(00)80010-4."},{"pmid":"33951361","citation":"Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, Svane MS, Bandholm T, Bojsen-Moller KN, Blond MB, Jensen JB, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730. doi: 10.1056/NEJMoa2028198."},{"pmid":"35658024","citation":"Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4."},{"pmid":"39344838","citation":"Dubin RL, Heymsfield SB, Ravussin E, Greenway FL. Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps. Diabetes Obes Metab. 2024 Dec;26(12):5503-5518. doi: 10.1111/dom.15913. Epub 2024 Sep 30."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07154719"},{"nctId":"NCT07340827","title":"A Study to Compare the Efficacy and Safety of Follitropin Alfa/Lutropin Alfa Versus hMG in Japanese Participants With LH and FSH Deficiency Undergoing ART (HINATA)","officialTitle":"A Parallel-group Treatment, 2-arm Study to Compare the Efficacy and Safety of Follitropin Alfa and Lutropin Alfa Fixed Dose Combination Versus hMG for Inducing Follicular Development in Japanese Participants With LH and FSH Deficiency Undergoing ART","summary":"The purpose of this study is to assess the efficacy and safety of follitropin alfa/lutropin alfa in Japanese participants with Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) deficiency undergoing Assisted reproductive technology (ART).\n\nThe study duration is approximately 5.5 months for nonpregnant participants and 13 months for participants with confirmed pregnancy in Part A.","detailedDescription":null,"peptideSlugs":["cetrorelix"],"peptideNames":["Cetrorelix"],"conditions":["Infertility"],"keywords":["Gonadotropins, infertility, prefilled pen"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany","slug":"merck-healthcare-kgaa-darmstadt-germany-an-affiliate-of-merck-kgaa-darmstadt-germany","class":"INDUSTRY"},"collaborators":[{"name":"Merck KGaA","slug":"merck-kgaa","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":266,"dates":{"start":"2026-02-04","primaryCompletion":"2028-07-05","completion":"2028-07-05","firstPosted":"2026-01-14","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":21,"countries":["Japan"],"locations":[{"facility":"Akita University Hospital - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Akita","state":"Akita","country":"Japan","latitude":39.71667,"longitude":140.11667},{"facility":"Kameda IVF Clinic Makuhari - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Chiba","state":"Chiba","country":"Japan","latitude":35.6,"longitude":140.11667},{"facility":"YOKOTA Maternity Hospital - Dept of Reproductive Medical Gynecology","status":"RECRUITING","city":"Maebashi","state":"Gunma","country":"Japan","latitude":36.4,"longitude":139.08333},{"facility":"Kamiya Ladies Clinic - Dept of Gynecology","status":"RECRUITING","city":"Sapporo","state":"Hokkaido","country":"Japan","latitude":43.06667,"longitude":141.35},{"facility":"Hanabusa Women's Clinic Hanabusa Women's Central Fertility Clinic - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Kobe","state":"Hyōgo","country":"Japan","latitude":34.6913,"longitude":135.183},{"facility":"Sophia Ladies Clinic - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Sagamihara-shi","state":"Kanagawa","country":"Japan","latitude":null,"longitude":null},{"facility":"Ladies Clinic Cosmos - Dept of Infertility Treatment","status":"RECRUITING","city":"Kochi","state":"Kochi","country":"Japan","latitude":33.55,"longitude":133.53333},{"facility":"Nagano Municipal Hospital - Dept of Gynecology","status":"RECRUITING","city":"Nagano","state":"Nagano","country":"Japan","latitude":36.65,"longitude":138.18333},{"facility":"JA-Nagano Shinonoi General Hospital - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Nagano","state":"Nagano","country":"Japan","latitude":36.65,"longitude":138.18333},{"facility":"Sora no Mori Clinic - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Shimajiri-gun","state":"Okinawa","country":"Japan","latitude":null,"longitude":null},{"facility":"Sankeikai IVF Osaka Clinic - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Higashiosaka-shi","state":"Osaka","country":"Japan","latitude":null,"longitude":null},{"facility":"Haruki Ladies Clinic - Dept of Gynecology","status":"RECRUITING","city":"Osaka","state":"Osaka","country":"Japan","latitude":34.69379,"longitude":135.50107},{"facility":"KASHIWAZAKI OB/GYN CLINIC - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Saitama-shi","state":"Saitama","country":"Japan","latitude":null,"longitude":null},{"facility":"Omiya Ladies Clinic - Dept of Gynecology","status":"RECRUITING","city":"Saitama-shi","state":"Saitama","country":"Japan","latitude":null,"longitude":null},{"facility":"Dokkyo Medical University Hospital - Dept of Reproduction Center","status":"RECRUITING","city":"Shimotsuga-gun","state":"Tochigi","country":"Japan","latitude":null,"longitude":null},{"facility":"Tokushima University Hospital - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Tokushima","state":"Tokushima","country":"Japan","latitude":34.06667,"longitude":134.56667},{"facility":"Juntendo University Hospital - Dept of Obstetrics/ Gynecology","status":"RECRUITING","city":"Bunkyō City","state":"Tokyo-To","country":"Japan","latitude":35.5331,"longitude":139.4217},{"facility":"University of Tokyo Hospital - Dept of Obstetrics","status":"RECRUITING","city":"Bunkyō City","state":"Tokyo-To","country":"Japan","latitude":35.5331,"longitude":139.4217},{"facility":"Sugiyama Clinic Marunouchi - Dept of Obstetrics/ Gynecology","status":"RECRUITING","city":"Chiyoda-ku","state":"Tokyo-To","country":"Japan","latitude":null,"longitude":null},{"facility":"Toho University Omori Medical Center - Dept of Obstetrics/Gynecology","status":"RECRUITING","city":"Ōta-ku","state":"Tokyo-To","country":"Japan","latitude":35.56126,"longitude":139.71605},{"facility":"Sugiyama Clinic Shinjuku - Dept of Reproductive Medical","status":"RECRUITING","city":"Shinjuku-ku","state":"Tokyo-To","country":"Japan","latitude":null,"longitude":null}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Participants who are premenopausal wishing to conceive\n* Participants with maximum 1 previous stimulation for assisted reproductive technology (ART) without pregnancy\n* Japanese Participants\n* Participants are women with Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) deficiency congenital or acquired\n* Participants have a vaginal ultrasound scan showing both ovaries and no clinically significant uterine abnormality and a normal antral follicle count (AFC) of at least 5 follicles 2 to 10 millimeter (mm) in diameter per ovary\n* A semen analysis of the male partner been performed within 3 months prior to signature of informed consent and suitable for assisted reproductive technology\n* Participants have a normal cervical ThinPrep® cytologic test, (TCT) or Pap smear within 12 months of Screening. If not available, a cervical smear will be performed as part of screening\n* Other protocol defined criteria may apply\n\nExclusion Criteria:\n\n* Participants with history of severe OHSS in any previous ovarian stimulation cycle\n* Participants with Polycystic ovarian syndrome (PCOS) according to Rotterdam modified definition\n* Participants with contraindication to treatment with gonadotropins, hypersensitivity to gonadotropins or to any of the excipients\n* Participants with presence of known or suspected gonadotropin- or estrogen dependent malignancy (example. ovarian-, uterine-, or mammary carcinoma)\n* Participants with ovarian enlargement or cyst of unknown etiology, or presence of an ovarian cyst greater than 25 millimeters before Day 1\n* other protocol defined exclusion criteria may apply","minimumAge":"18 Years","maximumAge":"42 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"COMBINATION_PRODUCT","name":"Follitropin alfa/lutropin alfa (MBJ-0011)","description":"Follitropin alfa and lutropin alfa will be administered subcutaneously once daily with a starting dose of 150 International Unit (IU) of follitropin alfa, 75 IU of lutropin alfa, in ovarian stimulation up to 18 days."},{"type":"DRUG","name":"hMG","description":"Participants will receive 150 IU as solvent, subcutaneously, for solution for injection, daily (up to 18 days) during ovarian stimulation."},{"type":"DRUG","name":"Cetrorelix acetate","description":"Participants will receive 250 micrograms (mcg) of Cetrorelix acetate as Powder for reconstitution to a solution for injection with diluent in ampule, daily from Day 5 or 6 of stimulation up to the day of r-hCG."},{"type":"DRUG","name":"Coriogonadotropin alfa","description":"Participants will receive 250 mcg of r-hCG, as solution for injection, subcutaneously, during final follicular maturation."},{"type":"DRUG","name":"Progesterone gel","description":"Participants will self-administer progesterone gel 8 percent, with an applicator, at a dose of 90 milligram (mg), intravaginally, daily from oocyte retrieval during Luteal phase support."}],"primaryOutcomes":[{"measure":"Total number of oocytes retrieved","description":"Mean number of oocytes retrieved will be calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.","timeFrame":"At approximately 36 to 38 hours after r-hCG administration (Day 4)"}],"secondaryOutcomes":[{"measure":"Total dose of gonadotropin (IU) used","description":"Total dose of Human Menopausal Gonadotropin (hMG) referred as IU of FSH.","timeFrame":"At Visit 3 after ovarian stimulation from Day 5 until Day of r-hCG (maximum 18 days)"},{"measure":"Number of Days of Gonadotropin Treatment","description":"Total number of days of ovarian stimulation will be reported.","timeFrame":"At Visit 3 after ovarian stimulation from Day 5-18"},{"measure":"Total Number of Follicles Measuring greater than or equal to 14 millimeter (mm) and greater than or equal to 17 mm in diameter","description":null,"timeFrame":"During Ovarian stimulation (Day 5 to Day 18)"},{"measure":"Serum Estradiol (E2) levels","description":null,"timeFrame":"At Visit 3 after ovarian stimulation from Day 5-18"},{"measure":"Proportion of 2 Pronuclei Embryos/Fertilized Oocytes","description":"The proportion of oocytes that fertilized after they were inseminated with the sperm will be reported.","timeFrame":"At 18 (Plus or minus two hours) hours after insemination"},{"measure":"Number of blastocysts frozen","description":"After the transfer of 1 fresh blastocysts - spare ones will be frozen.","timeFrame":"5 days after insemination"},{"measure":"Number of Participants With Clinical Pregnancy","description":"A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or with or without heartbeat (fetal sac).","timeFrame":"35-42 days after Visit 5 (Blastocyst transfer)"},{"measure":"Number of Participants With Ongoing Pregnancy","description":"Ongoing pregnancy will be confirmed with transvaginal ultrasound (TVUS) showing heartbeat.","timeFrame":"up to 80 days after blastocyst transfer (pregnancy week 11 to 12)"},{"measure":"Number of Participants With Treatment-Emergent Adverse Events and Treatment related Adverse Events","description":null,"timeFrame":"5.5 months for nonpregnant participants and 13 months for participants with confirmed pregnancy"},{"measure":"Number of Participants With Ovarian Hyperstimulation Syndrome (OHSS)","description":null,"timeFrame":"5.5 months for nonpregnant participants and 13 months for participants with confirmed pregnancy"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07340827"},{"nctId":"NCT07441876","title":"Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia","officialTitle":"A Multicenter, Randomized, Operationally Seamless Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia","summary":"This is a multicenter, multinational, randomized, active-controlled, operationally seamless Phase 2/3 study of BMN 333 in treatment-naïve pediatric participants with achondroplasia (ACH). The study consists of a Phase 2 part and a Phase 3 part.","detailedDescription":"The main purpose of this study is to evaluate the effects of BMN 333 on growth compared with vosoritide in participants with achondroplasia who have not received any growth-promoting treatments. The study includes 2 parts: the Phase 2 part will select the optimal BMN 333 dose to be used in Phase 3 and determine study continuation into Phase 3; the Phase 3 part will compare the effects of the selected dose of BMN 333 with vosoritide. Study details for either Phase 2 or Phase 3 include the following:\n\n* Study duration: up to 61 weeks (from screening to Safety Follow-up visit)\n* Treatment duration: 52 weeks. Treatment frequency: BMN 333, once weekly; vosoritide, once daily","peptideSlugs":["vosoritide"],"peptideNames":["Vosoritide"],"conditions":["Achondroplasia"],"keywords":["Achondroplasia","ACH","Bone Diseases, Developmental Dwarfism","Bone Diseases","Genetic Diseases, Inborn","Musculoskeletal Diseases","Natriuretic Peptide, C-type","Osteochondrodysplasias","Physiological Effects of Drugs","Skeletal Dysplasias"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"BioMarin","slug":"biomarin","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2","PHASE3"],"slugs":["phase-2","phase-3"],"labels":["Phase 2","Phase 3"],"label":"Phase 2 / Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":160,"dates":{"start":"2026-04-20","primaryCompletion":"2029-06","completion":"2029-09","firstPosted":"2026-03-02","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":19,"countries":["Australia","Canada","Italy","Japan","Poland","Romania","South Korea","United Kingdom","United States"],"locations":[{"facility":"UCSF Benioff Children's Hospital Oakland","status":"RECRUITING","city":"Oakland","state":"California","country":"United States","latitude":37.80437,"longitude":-122.2708},{"facility":"Nemours Children's Health","status":"NOT_YET_RECRUITING","city":"Wilmington","state":"Delaware","country":"United States","latitude":39.74595,"longitude":-75.54659},{"facility":"Ann & Robert H. Lurie Children's Hospital of Chicago","status":"RECRUITING","city":"Chicago","state":"Illinois","country":"United States","latitude":41.85003,"longitude":-87.65005},{"facility":"Johns Hopkins Medicine","status":"RECRUITING","city":"Baltimore","state":"Maryland","country":"United States","latitude":39.29038,"longitude":-76.61219},{"facility":"Cincinnati Children's Hospital Medical Center","status":"NOT_YET_RECRUITING","city":"Cincinnati","state":"Ohio","country":"United States","latitude":39.12711,"longitude":-84.51439},{"facility":"Children's Hospital of Philadelphia","status":"NOT_YET_RECRUITING","city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"University of Texas Southwestern Medical Center","status":"NOT_YET_RECRUITING","city":"Dallas","state":"Texas","country":"United States","latitude":32.78306,"longitude":-96.80667},{"facility":"Texas Children Hospital, Baylor College of Medicine","status":"RECRUITING","city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327},{"facility":"Consano Clinical Research, LLC","status":"RECRUITING","city":"San Antonio","state":"Texas","country":"United States","latitude":29.42412,"longitude":-98.49363},{"facility":"Murdoch Children's Research Institute","status":"RECRUITING","city":"Parkville","state":"Victoria","country":"Australia","latitude":-37.78333,"longitude":144.95},{"facility":"Universite de Montreal - Centre Hospitalier Universitaire Sainte-Justine","status":"NOT_YET_RECRUITING","city":"Montreal","state":"Quebec","country":"Canada","latitude":45.50884,"longitude":-73.58781},{"facility":"Irccs Ospedale Gaslini Di Genova","status":"NOT_YET_RECRUITING","city":"Genova","state":null,"country":"Italy","latitude":45.21604,"longitude":11.87211},{"facility":"Osaka City General Hospital","status":"RECRUITING","city":"Osaka","state":null,"country":"Japan","latitude":34.69379,"longitude":135.50107},{"facility":"Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii i Chorob Infekcyjnych","status":"NOT_YET_RECRUITING","city":"Wroclaw","state":null,"country":"Poland","latitude":51.10286,"longitude":17.03006},{"facility":"Institutul National de Endocrinologie C.I.Parhon","status":"NOT_YET_RECRUITING","city":"Bucharest","state":null,"country":"Romania","latitude":44.43225,"longitude":26.10626},{"facility":"Craiova Emergency Clinical County","status":"NOT_YET_RECRUITING","city":"Craiova","state":null,"country":"Romania","latitude":44.31667,"longitude":23.8},{"facility":"Seoul National University Hospital","status":"RECRUITING","city":"Seoul","state":null,"country":"South Korea","latitude":37.566,"longitude":126.9784},{"facility":"Pusan National University Yangsan Hospital","status":"NOT_YET_RECRUITING","city":"Yangsan","state":null,"country":"South Korea","latitude":35.34199,"longitude":129.03358},{"facility":"University Hospitals Bristol NHS Foundation Trust - Bristol Royal Hospital for Children","status":"NOT_YET_RECRUITING","city":"Bristol","state":null,"country":"United Kingdom","latitude":51.45523,"longitude":-2.59665}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Participants must be aged ≥ 2 to \\< 11 years (Phase 2) or ≥ 2 to \\< 18 years (Phase 3), at the time of signing the informed consent\n2. Participants must have ACH (confirmed by documented genetic testing) and open epiphyses\n3. Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)\n4. Are ambulatory and able to stand without assistance\n\nExclusion Criteria:\n\n1. Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)\n2. Have any of the following disorders: Hypothyroidism or hyperthyroidism, unless treated with evidence of normalized thyroid-stimulating hormone (TSH) levels, diabetes mellitus, unless considered well-controlled, autoimmune inflammatory disease, inflammatory bowel disease, autonomic neuropathy, anemia defined as hemoglobin \\< 10 g/dL, vitamin D deficiency, significant hip pathology.\n3. Have history of any renal insufficiency or cardiac/ cardiovascular disease that places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension.\n4. Have had bone fractures of the long bones or spine within 6 months prior to screening.\n5. Have used vosoritide, any other approved product (except GH, as detailed below), investigational product, or investigational medical device for the treatment of ACH or short stature at any time\n6. Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start","minimumAge":"2 Years","maximumAge":"17 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"BMN 333","description":"Administration: Weekly subcutaneous injection"},{"type":"DRUG","name":"Vosoritide Injection [Voxzogo]","description":"Administration: Daily subcutaneous injection"}],"primaryOutcomes":[{"measure":"Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data]","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 3: Annualized Growth Velocity (AGV) at Week 52","description":null,"timeFrame":"52 weeks"}],"secondaryOutcomes":[{"measure":"Phase 2: AGV at Weeks 26 and 52","description":null,"timeFrame":"26 and 52 weeks"},{"measure":"Phase 2: Change from Baseline in standing height","description":"Measured in centimeters","timeFrame":"26 and 52 weeks"},{"measure":"Phase 2: Change from Baseline in height Z-score","description":null,"timeFrame":"26 and 52 weeks"},{"measure":"Phase 2: Change from Baseline in upper to lower body segment ratio","description":null,"timeFrame":"26 and 52 weeks"},{"measure":"Phase 2: Incidence of adverse events (AEs)","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 2: Incidence of serious adverse events (SAEs)","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 2: Incidence of events of interest (EOIs)","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma","description":null,"timeFrame":"52 weeks"},{"measure":"Phase 2: Time to reach maximum concentration (Tmax) for BMN 333","description":null,"timeFrame":"52 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07441876"},{"nctId":"NCT07702461","title":"Determination of Resistance Training Status for Patients on Glucagon-Like Peptide-1 Receptor Agonists","officialTitle":"Determination of Resistance Training Status for Patients on Glucagon-Like Peptide-1 Receptor Agonists","summary":"This study examines how adults who take a GLP-1 receptor agonist medication (such as semaglutide \\[Ozempic, Wegovy, Rybelsus\\], liraglutide \\[Saxenda, Victoza\\], or tirzepatide \\[Mounjaro, Zepbound\\]) perform resistance (strength) training before and after starting their medication.\n\nGLP-1 medications are being prescribed more and more often to help people manage type 2 diabetes and lose weight. These medications work well, but a known side effect is that people can lose lean (muscle) tissue along with fat. Losing muscle can make it harder to move, do everyday tasks, and stay strong as we age. Resistance training, things like lifting weights, using resistance bands, or doing push-ups and squats, is the most effective way to keep and build muscle. Yet most adults in the United States do not meet the recommended amount of resistance training, and very little is known about the resistance training habits of people who take GLP-1 medications.\n\nThe purpose of this research is to systematically collect information from adults using GLP-1 medications so we can better understand: how often they do resistance training before and after starting the medication; what their sessions look like (frequency, duration, intensity, muscle groups); whether their resistance training is linked to how strong they feel and how well they can carry out daily activities; and what makes resistance training easier or harder while on a GLP-1 medication.\n\nFindings will help doctors, dietitians, exercise professionals, and researchers design better guidance and interventions to protect muscle mass, physical function, and quality of life in people using GLP-1 medications.\n\nWho can join: Adults 18 years or older who are currently taking a GLP-1 receptor agonist medication for type 2 diabetes, overweight or obesity, or weight management, and who have been on the medication for at least three months at a stable dose. Participants must be able to read and respond to the survey in English. People who are pregnant or planning bariatric surgery within the next three months are not eligible.\n\nWhat participants will do: The study is a single, anonymous, online survey. Interested individuals click the survey link, review a short consent page, and indicate their willingness to participate. Eligible participants then answer questions about their background, current health, GLP-1 medication and dose, resistance training habits before and after starting the medication, self-reported strength and function, and things that make resistance training easier or harder. There are no in-person visits, no exercise tests, and no blood draws.\n\nHow long it takes: About 10 minutes total, in one online session. There is no follow-up after the survey and no compensation is offered.\n\nData privacy: The survey is anonymous. No names, email addresses, or IP addresses are collected or linked to responses. The survey runs on Qualtrics, a secure, institution-approved platform hosted on Ohio State University servers.\n\nThe research team hopes to enroll up to 200-300 adults across the United States.","detailedDescription":"Background and Rationale Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone released from enteroendocrine cells after a meal. It slows gastric emptying, limits maximum nutrient absorption, and helps prevent weight gain. GLP-1's actions also include preventing beta-cell death, promoting beta-cell proliferation, and regulating glucose metabolism. Originally used to improve outcomes in people with type 2 diabetes, GLP-1 receptor agonists (GLP-1RAs) have increasingly been prescribed for chronic weight management in individuals with overweight or obesity, with agents such as liraglutide 3 mg and semaglutide 2.4 mg approved for people with a body mass index of at least 30 kg/m2, or 27 kg/m2 with weight-related comorbidities. From 2019 to 2023, use of GLP-1RAs for weight loss in the United States rose from approximately 21,000 to 174,000 users, an increase of more than 700%.\n\nA recognized side effect of GLP-1RA therapy is a reduction in lean tissue mass. Losses in lean mass can impair quality of life and physical function by decreasing strength, slowing gait speed, and increasing fatigue. Reductions in muscle mass may also heighten fall risk, worsen metabolic health, and limit patients' ability to perform activities of daily living independently.\n\nResistance training (RT) is the most effective strategy for preserving and building muscle mass and strength. The American College of Sports Medicine (ACSM) recommends that adults engage in RT at least 2-3 times per week at moderate to vigorous intensity, focusing on all major muscle groups. However, national surveillance data indicate that only about 30% of U.S. adults meet the muscle-strengthening guidelines. Despite emerging evidence that combining GLP-1RAs with structured exercise - particularly RT - can mitigate lean mass loss and optimize long-term metabolic and functional outcomes, little is known about patients' RT behavior before and after initiating GLP-1RA therapy.\n\nThis study aims to systematically collect self-reported data from adults using GLP-1RAs on their RT participation and adherence to ACSM-aligned guidelines before and after starting the medication, in order to identify gaps in RT engagement and generate practical recommendations for researchers and practitioners seeking to prevent lean mass loss, preserve physical function, and improve quality of life in this growing patient population.\n\nSpecific Aims and Hypotheses Aim 1: Quantify the prevalence of resistance training participation among adults using GLP-1RAs, both before and after initiating GLP-1RA therapy.\n\n* Hypothesis 1a: A minority of GLP-1RA users meet ACSM muscle-strengthening guidelines prior to starting the medication.\n* Hypothesis 1b: RT participation and adherence do not increase after GLP-1RA initiation and may decline in some patients.\n\nAim 2: Characterize patterns of RT dosage (frequency, intensity, type, and volume) in GLP-1RA users and compare them to ACSM-aligned recommendations.\n\n\\- Hypothesis 2: Most GLP-1RA users who report RT perform it at a frequency and intensity below ACSM guidelines for optimal lean mass preservation.\n\nAim 3: Explore associations between RT participation and self-reported outcomes related to lean mass preservation, physical function, and quality of life in GLP-1RA users.\n\n\\- Hypothesis 3: GLP-1RA users who meet RT guidelines report better perceived strength, functional capacity (e.g., ability to perform daily tasks), and health-related quality of life than those who do not perform RT.\n\nAim 4: Identify patient-reported barriers and facilitators to engaging in RT while using GLP-1RAs, to inform future intervention development.\n\n\\- Hypothesis 4: Common barriers will include lack of knowledge about RT benefits during GLP-1RA therapy, limited access to equipment or programs, and fear of injury.\n\nStudy Design This is a cross-sectional, anonymous, online survey study. Adults currently using GLP-1RAs will complete a single online questionnaire assessing RT participation before and after starting GLP-1RA therapy, RT dosage patterns, perceived functional and quality-of-life outcomes, and perceived barriers and facilitators to RT. There are no in-person visits, no interventions, and no biological specimen collection. All data are self-reported in one online session lasting approximately 10 minutes.\n\nRecruitment Potential participants will be identified through multiple channels, including: flyers and posters placed in relevant clinical settings (e.g., endocrinology, primary care); social media outreach (e.g., posts or advertisements targeting adults using GLP-1RAs); and clinic-based outreach in which the study team provides IRB-approved recruitment flyers and study links to participating clinic staff (e.g., front desk staff, providers, care coordinators) for posting in clinic waiting areas or distribution to potentially interested patients during routine visits. The study team will not pre-screen or identify patients via medical records, and clinic staff will not share any patient identifiers with the study team. Interested patients will self-refer by accessing the survey link from the flyer or handout. The study team will not access, request, or use any medical records or protected health information (PHI) for recruitment, screening, enrollment, or analysis.\n\nProcedures The full participant workflow is as follows: (1) potential participants encounter an IRB-approved recruitment flyer, poster, social media post/advertisement, or clinic-distributed handout describing the study and listing a secure survey URL and/or QR code; (2) interested individuals self-initiate contact by clicking the link or scanning the QR code on a device of their choice, at a time and place of their choosing; (3) the link directs them to the electronic informed consent page on the institution-approved survey platform (Qualtrics) hosted on Ohio State University secure servers; (4) individuals who indicate willingness to participate by selecting \"I agree to participate\" proceed to brief eligibility screening; (5) individuals who meet all inclusion and no exclusion criteria proceed automatically to the main questionnaire, while ineligible individuals are routed to a thank-you/exit message; (6) eligible participants complete the one-time questionnaire and exit the platform.\n\nThe main questionnaire assesses: demographic and general health information; current height and weight and weight at the time of GLP-1RA initiation; specific GLP-1RA medication, indication, start date, starting dose, and current dose; resistance training habits in a usual week before starting the GLP-1RA medication; resistance training habits in a usual week since starting the GLP-1RA medication; self-reported muscular strength, ability to perform activities of daily living, fatigue, overall health, and quality of life; and perceived barriers and facilitators to resistance training while using a GLP-1RA. Resistance training is assessed using the Muscle-Strengthening Exercise Questionnaire (MSEQ; Shakespear-Druery et al., 2022) Long Form, which captures frequency, session duration, intensity (0-10 OMNI-Resistance Exercise Scale), muscle groups targeted, and type of resistance exercise (weight machines, bodyweight exercises, resistance bands or free weights, and holistic exercises). Items are presented verbatim with the recall anchor adapted from \"in a usual week\" to \"in a usual week BEFORE you started your GLP-1 medication\" and \"in a usual week SINCE you started your GLP-1 medication\" to enable a within-person pre/post comparison.\n\nConsent Electronic informed consent will be obtained at the beginning of the online survey using the IRB-approved online consent script (HRP-537 template). Because the click-to-agree mechanism does not capture a legally valid electronic signature, a Waiver of Documentation of Consent under 45 CFR 46.117(c) has been granted. The research presents no more than minimal risk and involves no procedures for which written consent is normally required outside of the research context.\n\nPrivacy and Confidentiality The survey is anonymous. No direct or indirect identifiers (name, email address, IP address) are collected or linked to survey responses. Qualtrics is configured to disable IP address collection and to use anonymous response settings. Data are stored on secure, password-protected Ohio State University servers, in project folders restricted to authorized study personnel listed on the approved IRB protocol. The analytic dataset is anonymous and contains no identifiable components. Consistent with university policy, research data are retained for at least five years after study closure.\n\nSample Size The target sample size is 200-300 consented participants. This number was selected based on feasibility and the need for sufficient precision to estimate the prevalence of resistance training participation among adults using GLP-1RAs, and to allow exploratory comparisons between participants who do and do not meet resistance training guidelines. Eligibility screening occurs after electronic consent; every consented individual that meets eligibility criteria counts toward the 300-participant enrollment ceiling.\n\nStatistical Analysis Descriptive statistics will summarize participant demographics, GLP-1RA characteristics, and resistance training behaviors. Primary study questions will be addressed using paired analyses comparing resistance training status before and after GLP-1RA initiation. Categorical outcomes will be analyzed using McNemar's test, and continuous or ordinal outcomes using paired t-tests or Wilcoxon signed-rank tests based on data distribution. Associations between resistance training participation and self-reported outcomes (perceived strength, functional capacity, fatigue, quality of life) will be examined using bivariate comparisons and regression analyses. Open-ended responses, if collected, will be grouped using content analysis to identify common barriers and facilitators.\n\nR…","peptideSlugs":["tirzepatide","semaglutide","liraglutide","exenatide","dulaglutide","glucagon"],"peptideNames":["Tirzepatide","Semaglutide","Liraglutide","Exenatide","Dulaglutide","Glucagon"],"conditions":["Obesity & Overweight","Diabetes (DM)"],"keywords":["GLP-1","GLP-1 Receptor Agonist","GLP-1RA","Semaglutide","Liraglutide","Tirzepatide","Ozempic","Wegovy","Rybelsus","Mounjaro","Zepbound","Saxenda","Victoza","Muscle-strenghtening Exercise","MSEQ","Lean body mass","Sarcopenia","Muscle Preservation","Weight Loss","Weight Management","Resistance Training","Strength Training","Weightlifting","Exercise","Physical Activity","Body weight exercise","Pilates","Holistic Exercise","Physical Function","Activities of Daily Living","Quality of Life","Health Related Quality of Life","Glucagon-Like Peptide-1","Glucagon-Like Peptide-1 Receptor Agonist","Weight Loss Medication"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"muscle-growth","label":"Muscle growth"}],"sponsor":{"name":"Ohio State University","slug":"ohio-state-university","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":300,"dates":{"start":"2026-06-12","primaryCompletion":"2026-10","completion":"2027-01","firstPosted":"2026-07-14","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"The Ohio State University","status":"RECRUITING","city":"Columbus","state":"Ohio","country":"United States","latitude":39.96118,"longitude":-82.99879}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adult aged 18 years or older\n* Currently taking a GLP-1 receptor agonist medication\n* On the GLP-1 receptor agonist for at least 3 months\n* Using the GLP-1 receptor agonist for type 2 diabetes, overweight or obesity, and/or weight management (self-reported)\n* Stable GLP-1 receptor agonist dose for the past 4 to 8 weeks\n* Able to read and respond to the survey in English\n* Willing and able to provide informed consent electronically\n\nExclusion Criteria:\n\n* Currently or planning to become pregnant\n* Planned bariatric surgery within the next 3 months\n* Recent bariatric surgery (within the past 3 months) or other conditions that substantially alter resistance training capacity (e.g., advanced cancer cachexia, severe mobility-limiting conditions)\n* Unable to read or respond to the survey in English","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Glucagon-Like Peptide-1 Agonist (GLP-1)","description":"Adults currently taking a GLP-1 receptor agonist (GLP-1RA) medication for at least 3 months at a stable dose (e.g., semaglutide, liraglutide, tirzepatide, dulaglutide, or exenatide) complete a single, anonymous, online questionnaire administered via Qualtrics on Ohio State University secure servers. The survey (\\~10 minutes) collects self-reported data on demographics, general health, current GLP-1RA medication with starting and current dose, height and weight, resistance training habits in a usual week before and since starting GLP-1RA therapy (assessed with the Muscle-Strengthening Exercise Questionnaire - Long Form; Shakespear-Druery et al., 2022), perceived muscular strength, activities of daily living, fatigue, quality of life, and barriers/facilitators to resistance training. No in-person visits, physical measurements, biospecimen collection, or follow-up contact are performed."}],"primaryOutcomes":[{"measure":"Change in Resistance Training Status Before Versus Since GLP-1 Receptor Agonist Initiation","description":"Resistance training (RT) status is assessed via the Muscle-Strengthening Exercise Questionnaire - Long Form (MSEQ-Long; Shakespear-Druery et al., 2022), which captures weekly frequency (days/week), session duration (minutes/session), intensity (OMNI-RES 0-10 scale), muscle groups targeted (7 major groups), and type of muscle-strengthening exercise across four modes (weight machines, bodyweight, resistance bands or free weights, holistic). Each participant reports RT during a usual week BEFORE starting their GLP-1 receptor agonist medication and during a usual week SINCE starting the medication. The primary outcome is the proportion of participants meeting ACSM muscle-strengthening guidelines (≥ 2 days per week engaging all major muscle groups) at each recall period, and the within-person change between the two recall periods.","timeFrame":"Day 1"}],"secondaryOutcomes":[{"measure":"Resistance Training Dosage Patterns Compared to ACSM Guidelines","description":"Distributions of MSEQ-Long weekly frequency, session duration, intensity, muscle groups targeted, and exercise type, compared to ACSM adult muscle-strengthening recommendations, at each recall period.","timeFrame":"Day 1"}],"publications":[{"pmid":"39043396","citation":"Mahase E. GLP-1 agonists: US sees 700% increase over four years in number of patients without diabetes starting treatment. BMJ. 2024 Jul 23;386:q1645. doi: 10.1136/bmj.q1645. No abstract available."},{"pmid":"33239350","citation":"Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, Carty C, Chaput JP, Chastin S, Chou R, Dempsey PC, DiPietro L, Ekelund U, Firth J, Friedenreich CM, Garcia L, Gichu M, Jago R, Katzmarzyk PT, Lambert E, Leitzmann M, Milton K, Ortega FB, Ranasinghe C, Stamatakis E, Tiedemann A, Troiano RP, van der Ploeg HP, Wari V, Willumsen JF. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020 Dec;54(24):1451-1462. doi: 10.1136/bjsports-2020-102955."},{"pmid":"41843416","citation":"Currier BS, D'Souza AC, Singh MAF, Lowisz CV, Rawson ES, Schoenfeld BJ, Smith-Ryan AE, Steen JP, Thomas GA, Triplett NT, Washington TA, Werner TJ, Phillips SM. American College of Sports Medicine Position Stand. Resistance Training Prescription for Muscle Function, Hypertrophy, and Physical Performance in Healthy Adults: An Overview of Reviews. Med Sci Sports Exerc. 2026 Apr 1;58(4):851-872. doi: 10.1249/MSS.0000000000003897. Epub 2026 Mar 5."},{"pmid":"36841762","citation":"Sandsdal RM, Juhl CR, Jensen SBK, Lundgren JR, Janus C, Blond MB, Rosenkilde M, Bogh AF, Gliemann L, Jensen JB, Antoniades C, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial. Cardiovasc Diabetol. 2023 Feb 25;22(1):41. doi: 10.1186/s12933-023-01765-z."},{"pmid":"38629387","citation":"Bikou A, Dermiki-Gkana F, Penteris M, Constantinides TK, Kontogiorgis C. A systematic review of the effect of semaglutide on lean mass: insights from clinical trials. Expert Opin Pharmacother. 2024 Apr;25(5):611-619. doi: 10.1080/14656566.2024.2343092. Epub 2024 Apr 18."},{"pmid":"38937282","citation":"Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024 Sep;26 Suppl 4:16-27. doi: 10.1111/dom.15728. Epub 2024 Jun 27."},{"pmid":"35237446","citation":"Shakespear-Druery J, De Cocker K, Biddle SJH, Bennie J. Muscle-Strengthening Exercise Questionnaire (MSEQ): an assessment of concurrent validity and test-retest reliability. BMJ Open Sport Exerc Med. 2022 Feb 14;8(1):e001225. doi: 10.1136/bmjsem-2021-001225. eCollection 2022."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07702461"},{"nctId":"NCT07723820","title":"Glycemic Velocity and Early Retinal Microvascular Change With GLP-1RA Versus SGLT2i Initiation in Type 2 Diabetes (GLIDE)","officialTitle":"Glycemic Velocity as a Modifiable Determinant of Early Retinal Microvascular and Choroidal Change During Initiation of GLP-1 Receptor Agonist Versus SGLT2 Inhibitor Therapy in Type 2 Diabetes: A Prospective Multimodal Retinal Imaging Cohort Study (the GLIDE Study)","summary":"The GLIDE study looks at how the small blood vessels of the eye respond during the first months of a new diabetes medicine. Two widely used classes of glucose-lowering drugs, GLP-1 receptor agonists and SGLT2 inhibitors, are compared in adults with type 2 diabetes who have no diabetic retinopathy or only early (mild) diabetic retinopathy.\n\nWhen blood sugar (HbA1c) falls quickly after starting treatment, the retina can undergo a brief, temporary worsening before it stabilizes and benefits over the long term. This study asks whether it is the speed of that blood-sugar reduction, which we call \"glycemic velocity,\" rather than the specific drug, that drives early changes in retinal and choroidal blood flow.\n\nParticipants are patients whose own physician has decided, independently of the study, to start one of these two drugs for the first time. The study does not choose, provide, or change any medicine; it adds only eye imaging, blood tests, and observation. Each participant is followed with specialized, non-invasive eye scans, optical coherence tomography angiography (OCT-A) and structural/choroidal OCT, together with HbA1c and other measurements, at the start of treatment and again over the following months.\n\nThe main measurement is the change, from the start of treatment to month 3, in the density of the tiny deep-layer capillaries at the center of the retina, measured on OCT-A. The study will test whether faster HbA1c reduction is linked to greater early change in these vessels and, using statistical mediation analysis, will estimate how much of any difference between the two drug groups is explained by glycemic velocity versus a direct drug effect.\n\nIf glycemic velocity, a factor physicians can influence by adjusting how quickly treatment is intensified, turns out to drive early retinal change, the findings could guide safer treatment strategies and help identify patients who need closer eye monitoring when starting these medicines.","detailedDescription":"Background and rationale:\n\nGLP-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are central therapies for type 2 diabetes, and their ocular safety remains unresolved. The cardiovascular outcome trial SUSTAIN-6 reported more adjudicated diabetic-retinopathy complications with semaglutide than placebo, concentrated among patients with pre-existing retinopathy and concurrent insulin use, whereas large real-world datasets have not reproduced a consistent signal. Mechanistic and meta-analytic work increasingly attributes the trial signal not to the molecule itself but to the magnitude and rapidity of the accompanying fall in glycated hemoglobin (HbA1c), the long-recognized phenomenon of transient \"early worsening\" of retinopathy after rapid glycemic correction, first characterized in the Oslo study and subsequently in the DCCT.\n\nCentral hypothesis and definition of the exposure:\n\nThe study formalizes the driver of early worsening as a continuous, patient-level exposure termed glycemic velocity: the rate at which HbA1c falls after treatment initiation, computed as (HbA1c at baseline - HbA1c at Month 3) divided by elapsed time and expressed in percentage points per month. It is analyzed per +1 SD, with a clinically anchored secondary scale of +0.5 percentage points per month and a pre-specified test for non-linearity or a threshold effect. Baseline HbA1c and the absolute magnitude of HbA1c reduction are retained as separate covariates so that the effect of rate is distinguished from that of magnitude and of starting level. The complementary mechanistic hypothesis is that a transient disturbance of retinal and choroidal perfusion (relative hypoxia) is the shared intermediate underlying GLP-1RA-associated ocular signals, and that its magnitude tracks with glycemic velocity.\n\nRationale for the design:\n\nDrug choice is made by the treating physician on clinical grounds; the study assigns, provides, and alters no therapy, adding only observation, imaging, and data collection. A new-user, active-comparator structure is used because enrolling only treatment-naive initiators removes prevalent-user and immortal-time biases, while an active comparator rather than non-users minimizes confounding by indication and the healthy-user effect. SGLT2i was selected as the comparator because it shares the glucose-lowering indication and a broadly comparable position in contemporary treatment algorithms, yet is not classically implicated in early retinopathy worsening, providing the contrast needed to separate a drug-specific retinal effect from the drug-independent consequence of rapid glycemic correction. Because glycemic velocity is a continuous measured variable present in both groups, the primary hypothesis remains testable irrespective of how patients were allocated to drug class. Enrollment into each group is capped to preserve balance for the between-group comparison. Both eyes are imaged, with the eye-visit as the unit of observation and statistical accounting for inter-eye correlation.\n\nVisit schedule and data acquisition:\n\nPatients are identified at the point of treatment initiation and referred the same day, or within the permitted baseline window, for screening and baseline imaging. Assessments occur at Baseline (V0), Month 1 (V1, plus or minus 2 weeks), and Month 3 (V2, plus or minus 2 weeks), with a pre-planned companion analysis of longer-term trajectory over an extended follow-up described in the protocol. All imaging is performed on a single OCT-angiography/OCT platform by trained operators using a fixed acquisition protocol, and only scans meeting a pre-specified signal-strength and artifact threshold are analyzed. Quantitative metrics are produced by validated device software, with choroidal indices derived by standardized image binarization. Two independent graders, masked to drug class, glycemic data, and visit sequence, perform ETDRS grading and quality control, with senior adjudication of discrepancies; inter- and intra-grader reliability is quantified on a randomly selected double-graded subset using intraclass correlation coefficients and weighted kappa, against a pre-specified target. Data are captured in REDCap with role-based access rights and a full audit trail, and the metabolic and imaging datasets are reconciled only at the analysis stage.\n\nSample-size justification:\n\nEnrolment is governed by the between-group contrast in the primary outcome: detecting a difference of 2.0 percentage points (SD 3.5; Cohen's d approximately 0.57) at a two-sided alpha of 0.05 with 80% power requires approximately 49 participants per group. This exceeds the requirement for the primary association (approximately 62 participants for a partial correlation of r = 0.35, by Fisher's z-transformation) and therefore governs, and is inflated by approximately 20% for anticipated attrition and ungradable imaging. Repeated measures and the use of both eyes further increase effective precision. A non-inferential feasibility review after 40 participants complete Month 3 assesses imaging gradability, recruitment rate, and the plausibility of the assumed effect sizes; no efficacy stopping rule applies.\n\nStatistical analysis:\n\nThe primary analysis fits a linear mixed-effects model of the primary outcome over time, with the glycemic velocity by time interaction as the principal test, adjusted for drug class and for pre-specified confounders (age, sex, diabetes duration, baseline retinopathy severity, baseline HbA1c, magnitude of HbA1c reduction, blood pressure, eGFR, axial length, and OCT-angiography signal strength), and with random intercepts for participant and for eye nested within participant. The model uses all available eye-visit observations under a missing-at-random assumption. A causal mediation analysis in the counterfactual framework decomposes the total effect of drug class on the primary outcome into a natural indirect effect transmitted through glycemic velocity and a natural direct, unmediated effect; exposure-mediator interaction is permitted, and inference uses bootstrap confidence intervals with E-value sensitivity analysis for unmeasured mediator-outcome confounding. Baseline balance between groups is summarized using standardized mean differences rather than significance tests, and propensity-score methods (overlap weighting or matching) serve as a confounding-control sensitivity analysis. Pre-specified effect modification by baseline retinopathy severity and by insulin co-therapy is tested through interaction terms and interpreted as hypothesis-generating. Analyses follow a statistical analysis plan finalized and signed before database lock, are conducted in R or Stata, and are reported in accordance with STROBE and, for the mediation component, AGReMA.","peptideSlugs":["glucagon"],"peptideNames":["Glucagon"],"conditions":["Type 2 Diabetes Mellitus","Diabetic Retinopathy (DR)"],"keywords":["glycemic velocity","GLP-1 receptor agonist","SGLT2 inhibitor","OCT angiography","deep capillary plexus","retinal vessel density","foveal avascular zone","choroidal vascularity index","diabetic retinopathy","early worsening diabetic retinopathy","new-user active-comparator","causal mediation","retinal perfusion"],"conditionGroups":[{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Thammasart University Hospital","slug":"thammasart-university-hospital","class":"OTHER"},"collaborators":[{"name":"Thammasat University Hospital","slug":"thammasat-university-hospital","class":"OTHER"},{"name":"Thammasat University","slug":"thammasat-university","class":"OTHER"}],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":126,"dates":{"start":"2026-09-01","primaryCompletion":"2027-06-01","completion":"2027-09-01","firstPosted":"2026-07-23","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":1,"countries":["Thailand"],"locations":[{"facility":"Faculty of Medicine, Thammasat University","status":null,"city":"Pathum Thani","state":"Khlong Luang","country":"Thailand","latitude":14.01346,"longitude":100.53049}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Adults aged 18 years or older with a documented diagnosis of type 2 diabetes mellitus.\n* Clinical decision, made by the treating physician independently of the study, to initiate a first-ever GLP-1 receptor agonist or a first-ever SGLT2 inhibitor.\n* Baseline retinal status ranging from no diabetic retinopathy to mild non-proliferative diabetic retinopathy (NPDR) in the study eye(s), confirmed by fundus photography / ETDRS grading.\n* Baseline HbA1c within a range permitting a measurable subsequent change (e.g., 7.0% or higher), obtained within 30 days before or after the scheduled ophthalmic assessment.\n* Media sufficiently clear and fixation adequate to obtain gradable OCT-A and OCT images.\n* Able and willing to provide written informed consent and to attend scheduled follow-up visits.\n\nExclusion Criteria:\n\n* Moderate-to-severe NPDR, proliferative diabetic retinopathy, or center-involving diabetic macular edema at baseline.\n* Prior or concurrent treatment for diabetic retinopathy or maculopathy: pan-retinal or focal/grid laser photocoagulation, intravitreal anti-VEGF or corticosteroid therapy, or vitreoretinal surgery.\n* Any prior exposure to a GLP-1 receptor agonist or SGLT2 inhibitor (to preserve the new-user design).\n* Type 1 diabetes, latent autoimmune diabetes of adults, or secondary diabetes.\n* Other retinal or choroidal disease that would confound microvascular/choroidal measurement: age-related macular degeneration, retinal vein or artery occlusion, uveitis, high myopia (spherical equivalent more negative than -6.0 D or axial length greater than 26.0 mm), or significant media opacity precluding imaging.\n* Coexisting glaucoma or optic neuropathy that independently alters retinal vascular or neural metrics.\n* Recent (within 3 months) intraocular surgery in the study eye, including cataract surgery.\n* Uncontrolled systemic hypertension or a known systemic condition (e.g., significant anemia, severe renal impairment with eGFR \\< 30 mL/min/1.73 m², or active malignancy) that independently affects retinal perfusion or oximetry, at investigator discretion.\n* Pregnancy, or planned simultaneous initiation of insulin such that the index glucose-lowering exposure cannot be attributed (concurrent stable insulin is permitted and recorded as a pre-specified effect modifier).\n* Inability to provide informed consent or to comply with the imaging and follow-up schedule.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"GLP-1 Receptor Agonists","description":"First-ever GLP-1 receptor agonist initiated as routine clinical care; class and rate of titration are recorded but not controlled by the study. Mapped to Cohort 1."},{"type":"DRUG","name":"SGLT2 inhibitor","description":"First-ever SGLT2 inhibitor initiated as routine clinical care; recorded but not controlled by the study. Mapped to Cohort 2."}],"primaryOutcomes":[{"measure":"Change in parafoveal deep-capillary-plexus (DCP) vessel density on OCT angiography","description":"Vessel density (%) of the deep capillary plexus in the parafoveal ring on OCT angiography (fixed macular scan, validated quantification, pre-specified image-quality threshold, masked grading); primary metric is the change from baseline to Month 3.","timeFrame":"Baseline to Month 3"}],"secondaryOutcomes":[{"measure":"Superficial capillary plexus (SCP) vessel density and perfusion density","description":"SCP vessel density and perfusion density (%) in standardized macular sectors on OCT angiography.","timeFrame":"Baseline to Month 3"},{"measure":"Foveal avascular zone (FAZ) area","description":"FAZ area (mm²) by automated or masked manual delineation on OCT angiography.","timeFrame":"Baseline to Month 3"},{"measure":"Subfoveal choroidal thickness","description":"Vertical distance from the outer RPE to the chorioscleral interface at the fovea (µm) on EDI-OCT.","timeFrame":"Baseline to Month 3"},{"measure":"Choroidal vascularity index (CVI)","description":"Ratio of luminal to total choroidal area (%) by standardized image binarization on EDI-OCT; indexes the choroidal / hypoxia arm of the mechanism.","timeFrame":"Baseline to Month 3"},{"measure":"Central subfield thickness","description":"Mean retinal thickness of the central 1-mm ETDRS subfield (µm) on SD-OCT; surrogate for incipient macular edema.","timeFrame":"Baseline to Month 3"},{"measure":"Best-corrected visual acuity (BCVA)","description":"logMAR acuity by ETDRS protocol refraction; functional correlate.","timeFrame":"Baseline to Month 3"},{"measure":"Proportion of drug-class effect mediated by glycemic velocity","description":"From causal mediation analysis: the proportion of any between-group (GLP-1RA vs SGLT2i) difference in early DCP vessel-density change that is transmitted through glycemic velocity (natural indirect effect) versus a direct, unmediated drug-class effect.","timeFrame":"Baseline to Month 3"},{"measure":"Diabetic-retinopathy severity step-change (ETDRS)","description":"Change in ETDRS diabetic-retinopathy level by masked grading of fundus photographs; ≥ 1-step and ≥ 2-step worsening or improvement.","timeFrame":"Baseline to Month 3"}],"publications":[{"pmid":"18064739","citation":"von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct 20;370(9596):1453-7. doi: 10.1016/S0140-6736(07)61602-X."},{"pmid":"38584180","citation":"Eleftheriadou A, Riley D, Zhao SS, Austin P, Hernandez G, Lip GYH, Jackson TL, Wilding JPH, Alam U. Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database. Diabetologia. 2024 Jul;67(7):1271-1282. doi: 10.1007/s00125-024-06132-5. Epub 2024 Apr 8."},{"pmid":"37454782","citation":"Kapoor I, Sarvepalli SM, D'Alessio D, Grewal DS, Hadziahmetovic M. GLP-1 receptor agonists and diabetic retinopathy: A meta-analysis of randomized clinical trials. Surv Ophthalmol. 2023 Nov-Dec;68(6):1071-1083. doi: 10.1016/j.survophthal.2023.07.002. Epub 2023 Jul 16."},{"pmid":"9682700","citation":"Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998 Jul;116(7):874-86. doi: 10.1001/archopht.116.7.874."},{"pmid":"30226298","citation":"Bain SC, Klufas MA, Ho A, Matthews DR. Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review. Diabetes Obes Metab. 2019 Mar;21(3):454-466. doi: 10.1111/dom.13538. Epub 2018 Oct 15."},{"pmid":"27633186","citation":"Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15."},{"pmid":"41501669","citation":"Luo Y, Xia Y, Gong X, Hao M, Wei Q, Liao L. GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential. BMC Ophthalmol. 2026 Jan 8;26(1):12. doi: 10.1186/s12886-025-04559-x."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07723820"},{"nctId":"NCT07724340","title":"A Study to Assess the Efficacy, Safety and Tolerability of AT673 Co-administered With Semaglutide in Adult Participants With Type 2 Diabetes (T2D) and Overweight or Obesity","officialTitle":"A Phase 2, Randomized, Double-blind, Placebo-Controlled, Multi-center Study to Assess the Efficacy, Safety and Tolerability of AT673 Co-administered With Semaglutide in Adult Participants With Type 2 Diabetes (T2D) and Overweight or Obesity","summary":"The goal of this clinical trial is to learn if AT673 contributes to additional weight loss and glycemic control when given with semaglutide in participants with overweight/obesity and type 2 diabetes. The main questions it aims to answer are:\n\n* To compare the effect on body weight of two doses of AT673 once-weekly versus matched placebo when concurrently administered with semaglutide once-weekly\n* To evaluate the effect of AT673 on glycated hemoglobin (HbA1c)\n* To compare the safety and tolerability of AT673 versus matched placebo when concurrently administered with semaglutide","detailedDescription":"This is a phase 2, double-blind, placebo-controlled study. Following screening, at their baseline visit, participants will initiate treatment with semaglutide at 0.25 mg/week and follow the product labelled dose escalation schedule until reaching the dose of 1.0 mg/week. Participants will remain on this dose until the end of study (EOS) visit.\n\nAt the baseline visit, participants will be randomized in a 1:1:1 ratio to receive AT673 25 mg, or 50 mg, or matching placebo, respectively, once weekly at the same time as semaglutide.\n\nParticipants will receive AT673 / placebo injections concurrently with Semaglutide during weekly clinic visits. Treatment with the AT673 / placebo will continue through the end of 13 weeks. This will be followed by a 4-week safety follow-up. The end of study visit will be at week 17.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Adults With Overweight/Obesity and Type 2 Diabetes"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Antag Therapeutics","slug":"antag-therapeutics","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":150,"dates":{"start":"2026-06-19","primaryCompletion":"2027-02","completion":"2027-03","firstPosted":"2026-07-24","resultsPosted":null,"lastUpdated":"2026-07-24"},"hasResults":false,"locationCount":8,"countries":["United States"],"locations":[{"facility":"CenExel Phoenix","status":"RECRUITING","city":"Chandler","state":"Arizona","country":"United States","latitude":33.30616,"longitude":-111.84125},{"facility":"CenExel Anaheim","status":"RECRUITING","city":"Anaheim","state":"California","country":"United States","latitude":33.83529,"longitude":-117.9145},{"facility":"CenExel Hollywood","status":"RECRUITING","city":"Hollywood","state":"Florida","country":"United States","latitude":26.0112,"longitude":-80.14949},{"facility":"CenExel Tampa","status":"RECRUITING","city":"Tampa","state":"Florida","country":"United States","latitude":27.94752,"longitude":-82.45843},{"facility":"CenExel Atlanta","status":"RECRUITING","city":"Atlanta","state":"Georgia","country":"United States","latitude":33.749,"longitude":-84.38798},{"facility":"CenExel Decatur","status":"RECRUITING","city":"Decatur","state":"Georgia","country":"United States","latitude":33.77483,"longitude":-84.29631},{"facility":"CenExel Savannah","status":"RECRUITING","city":"Savannah","state":"Georgia","country":"United States","latitude":32.08354,"longitude":-81.09983},{"facility":"CenExel SLC","status":"RECRUITING","city":"Salt Lake City","state":"Utah","country":"United States","latitude":40.76078,"longitude":-111.89105}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Signed informed consent prior to start the Screening Visit procedures.\n2. Female and male participants ≥18 years of age at time of consent\n3. BMI g ≥27.0 kg/m2 at screening.\n4. HbA1c ≥7 and ≤10% (53-86 mmol/mol) at screening.\n5. Diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening.\n6. Either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, sulfonylurea, and/or DPP4 inhibitor as monotherapy or combination therapy, per approved local label.\n\n   a) Note: Participants treated with sulfonylureas and/or DPP4 inhibitors must discontinue these at least 24 hours prior to initiation of semaglutide.\n7. Participant has had at least 1 unsuccessful attempt at weight loss by diet and exercise in the opinion of the investigator.\n8. Women of childbearing potential (WOCBP) meeting the criteria below:\n\n   i) Non-lactating and has a negative pregnancy test at screening and baseline -AND- ii) Uses an acceptable method of contraception as determined by the Investigator or Sub-Investigator for the duration of the study and 30 days following the last dose of study drug\n9. Participants must, in the opinion of the Investigator, be suitable candidates to receive semaglutide (Wegovy®) as indicated according to the product label.\n\nExclusion Criteria:\n\n1. Participant has had gastric bypass or other bariatric surgery or endoscopic procedure or any metabolic procedures (e.g. duodenal resurfacing, intragastric balloon, etc.) except for the following:\n\n   1. Liposuction and/or abdominoplasty that was performed \\> 1 year before screening\n   2. Laparoscopic gastric band that was removed \\> 1 year before screening\n   3. Intragastric balloon that was removed \\> 1 year before screening\n   4. Duodenal-jejunal bypass sleeve that was removed \\> 1 year before screening.\n2. Participant has had a self-reported or medically recorded change in body weight \\> 5% within 3 months of screening OR has recorded change in body weight \\>3% between screening and randomization.\n3. Participant is currently using insulin or used insulin within 3 months before screening.\n4. Participant is currently using sulfonylureas and/or DPP4 inhibitors and is unable or unwilling to discontinue the use of these medications at least 24 hours prior to initiation of semaglutide.\n5. Participant has a form of diabetes other than type 2.\n\n   a. Note: Previous diagnosis of gestational diabetes is permitted so long as the participant meets all inclusion and none of the exclusion criteria.\n6. Participant is currently using or used within 3 months before screening any weight reducing medication including pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, bupropion.\n7. Participant is currently using or used within 6 months before screening any medication that contains a GLP-1R agonist component or a GIPR modulator (either by prescription or as part of a clinical study)\n8. For participants with a history of prior GLP-1R agonist use (\\> 6 months prior to screening):\n\n   1. Participant has had a previous intolerance or hypersensitivity to GLP-1 receptor agonists or any of its excipients.\n   2. Participant has previously discontinued a GLP-1 receptor agonist after continuous treatment for 6 months or longer due to not meeting personal weight loss goals.\n9. Participant is taking any medication that, may cause weight gain unless the participant has used these medications for more than 6 months at a stable dose prior to screening.\n10. Participant has hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase levels \\>2.5, or total bilirubin levels \\> 1.5 times the upper limit of normal (ULN) at screening.\n11. Participant's current alcohol intake exceeds 14 units/week for men or 7 units/week for women (1 unit = half pint of beer, 1 glass of wine, 1 measure of spirits).\n12. Participant has a recent history of illicit substance use (\\< 3 months) or in the opinion of the Investigator suspicion of current illicit substance use.\n13. Participant has uncontrolled hypertension at screening (SBP above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg).\n14. A corrected QT interval (QTc) of \\> 450 msec in males or \\> 470 msec in females at screening, or history of long QT syndrome.\n15. Concurrent participation in another interventional study (e.g., of a drug, over the counter product, device) or within ≤90 days or 5 half-lives prior to Screening.\n16. Participant is unable to understand and communicate with the investigators; or to understand the protocol requirements, instructions, study-related restrictions, nature, scope, and possible consequences of the clinical study; or is unlikely to comply with the study requirements (e.g., uncooperative attitude and improbability of completing the clinical study).\n17. Participant is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the study, or employee of the sponsor, site, or Contract Research Organization (CRO).\n18. Participant whose obesity can be traced to a medical cause, suggestive of genetic or syndromic obesity of an endocrinologic disorder (e.g., hypothyroidism, Cushings syndrome, Prader-Willi syndrome).\n19. Participant has a history of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years, except for basal cell carcinoma.\n20. Participant has a glomerular filtration rate \\< 60 mL/min/1.73 m2.\n21. Participant has a history of major psychiatric disorders within 5 years or lifetime history of suicide attempt.\n22. Participant has any suicidal ideation of type 4 or 5 on the C-SSRS at screening.\n23. Participant with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia (MEN) syndrome type 2.\n24. Participant with a previous history of chronic pancreatitis, or acute pancreatitis within 6 months prior to screening.\n25. In the opinion of the Investigator, any disorder, condition, inability or unwillingness not covered by the exclusion criteria that may interfere with study procedures, assessments or participant's safety.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"AT673 low dose","description":"low dose"},{"type":"DRUG","name":"AT673 high dose","description":"high dose"},{"type":"DRUG","name":"Placebo","description":"matching placebo"}],"primaryOutcomes":[{"measure":"Body weight","description":"Percent change in body weight from baseline to week 13","timeFrame":"13 weeks"}],"secondaryOutcomes":[{"measure":"HbA1c","description":"Absolute change from baseline to week 13 in blood concentration of HbA1c (%, mmol/mol)","timeFrame":"13 weeks"},{"measure":"Safety and Tolerability","description":"Frequency, severity and seriousness of treatment emergent AEs","timeFrame":"13 weeks"},{"measure":"Achieving clinically significant body weight loss from baseline to week 13","description":"Proportion of participants achieving \\>5%, and \\>10% body weight loss from baseline to week 13","timeFrame":"week 13"},{"measure":"Assess treatment effect on Body Mass Index","description":null,"timeFrame":"13 weeks"},{"measure":"Assess the treatment effect on insulin","description":null,"timeFrame":"13 weeks"},{"measure":"Assess the treatment effect on blood pressure","description":null,"timeFrame":"13 weeks"},{"measure":"Assess the treatment effect on markers of inflammation (hsCRP)","description":null,"timeFrame":"13 weeks"},{"measure":"Assess the treatment effect on lipid parameters","description":null,"timeFrame":"13 weeks"},{"measure":"Assess treatment effect on waist circumference","description":null,"timeFrame":"13 weeks"},{"measure":"Assess the treatment effect on fasting plasma glucose","description":null,"timeFrame":"13 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07724340"},{"nctId":"NCT04789148","title":"Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency","officialTitle":"Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency - A Pilot Study","summary":"This is a randomized, double-blind, placebo-controlled crossover pilot study of single-dose intranasal oxytocin (6 IU and 24 IU) vs. placebo in adult men and women (aged 18 years and above) with arginine-vasopressin deficiency to evaluate the effect of oxytocin on anxiety, depression, and socioemotional functioning (Part A), with an optional randomized, double-blind, placebo-controlled 2-week repeated dose substudy of intranasal oxytocin 6 IU or placebo (Part B).\n\nFollowing a screening visit to determine eligibility, participants will return for three main study visits in Part A. During the main study visits, study participants will receive either oxytocin or placebo, followed by assessments of emotional behavior.\n\nIn Part A, thirty participants will be equally randomized to one of six possible groups:\n\n1. 6 IU oxytocin - 24 IU oxytocin - placebo\n2. 6 IU oxytocin - placebo - 24 IU oxytocin\n3. 24 IU oxytocin - 6 IU oxytocin - placebo\n4. 24 IU oxytocin - placebo - 6 IU oxytocin\n5. placebo - 6 IU oxytocin - 24 IU oxytocin\n6. placebo - 24 IU oxytocin - 6 IU oxytocin\n\nFollowing completion of the Part A crossover portion of the study, in Part B participants may also choose to continue participation in an optional, randomized, double-blind, placebo-controlled substudy of intranasal oxytocin 6 IU or placebo three times a day for two weeks, followed by assessments of emotional behavior.","detailedDescription":null,"peptideSlugs":["vasopressin","oxytocin"],"peptideNames":["Vasopressin","Oxytocin"],"conditions":["Vasopressin Deficiency"],"keywords":["Hypopituitarism","posterior pituitary","oxytocin","psychopathology","anxiety","depressive symptoms","socioemotional functioning"],"conditionGroups":[{"slug":"brain-health","label":"Brain health"}],"sponsor":{"name":"Elizabeth Austen Lawson","slug":"elizabeth-austen-lawson","class":"OTHER"},"collaborators":[{"name":"Tonix Pharmaceuticals, Inc.","slug":"tonix-pharmaceuticals-inc","class":"INDUSTRY"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":40,"dates":{"start":"2025-09-10","primaryCompletion":"2027-06","completion":"2027-06","firstPosted":"2021-03-09","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Massachusetts General Hospital, Neuroendocrine Unit","status":"RECRUITING","city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Age 18 and above\n* Arginine-vasopressin deficiency\n* Normal FT4 or T4\n* Normal serum/plasma sodium\n* Stable hormone replacement\n\nExclusion Criteria:\n\n* Active substance use disorder within the last 6 months\n* History of psychosis\n* Suicidal behavior and/or active suicidal ideation with plan and/or intent, e.g., suicidal ideation of type 4 or type 5 as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS), in the last month\n* Medication changes within 4 weeks of enrollment or planned medication changes during the study\n* History of chronic nasal obstruction or local pathology in nostril pathway which, in the opinion of the investigator, would prevent appropriate nasal administration of the study drug.\n* History of cardiac disease, including arrhythmias, coronary heart disease, coronary artery spasms, valvular heart disease, hypertrophic cardiomyopathy (hypertension is not exclusionary)\n* History of chronic kidney disease stage III and above\n* History of liver cirrhosis\n* Pregnancy or breastfeeding within the last 8 weeks\n* Unwilling to use a medically acceptable form of contraception throughout the study period (female of child-bearing potential only)\n* Any significant illness, condition, drug or medical device that the Investigator determines could interfere with study participation, data collection, or safety","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Intranasal Oxytocin (IN-OXT)","description":"6 IU single dose"},{"type":"DRUG","name":"Intranasal Oxytocin (IN-OXT)","description":"IN-OXT 6 IU three times a day for 2 weeks"},{"type":"DRUG","name":"Placebo","description":"Intranasal placebo three times a day for 2 weeks"},{"type":"DRUG","name":"Intranasal Oxytocin (IN-OXT)","description":"24 IU single dose"},{"type":"DRUG","name":"Placebo","description":"placebo single dose"}],"primaryOutcomes":[{"measure":"Dot-probe task - anxious behavior between low dose oxytocin and placebo","description":"Difference in response times (in milliseconds) to dots appearing in the location of the previously shown negative versus the neutral face between 6 IU oxytocin vs placebo in the dot-probe task.","timeFrame":"20 minutes following intervention at each main visit"}],"secondaryOutcomes":[{"measure":"Dot-probe task - anxious behavior between all three interventions","description":"Difference in response time (in milliseconds) to dots appearing in the location of the previously shown negative versus neutral face between 6 IU oxytocin, 24 IU oxytocin, and placebo in the dot-probe task.","timeFrame":"20 minutes following intervention"},{"measure":"Depressive behavior - probabilistic reward task between all three interventions","description":"Response bias developed toward the more frequently reinforced alternative between 6 IU oxytocin, 24 IU oxytocin, and placebo in the probabilistic reward task.","timeFrame":"30 minutes following intervention at each main visit"},{"measure":"Socioemotional functioning - Emotion recognition task between all three interventions","description":"Accuracy in identifying correct emotion between 6 IU oxytocin, 24 IU oxytocin, and placebo in the emotion recognition task.","timeFrame":"40 minutes following intervention at each main visit"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT04789148"},{"nctId":"NCT05040087","title":"Changing the Natural History of Type 2 Diabetes (\"CHANGE\" Study)","officialTitle":"Changing the Natural History of Type 2 Diabetes (\"CHANGE\" Study)","summary":"Diabetes is a disorder of high blood glucose, that tends to get worse; over time, patients need more and more drugs. This pattern is caused by overwork of the body's insulin-producing β-cells, because patients' glucose levels are typically above normal; if the investigators kept glucose levels normal - reducing β-cell work - the investigators might be able to keep the disease from getting worse. This trial is aimed to show that adjusting the drugs to keep glucose levels normal, can help to preserve β-cell function compared to usual diabetes care, possibly reduce the tendency to develop the eye and kidney complications of diabetes, and might also be more cost-effective than usual care.","detailedDescription":"I. RATIONALE AND SPECIFIC AIMS CHANGING THE NATURAL HISTORY OF TYPE 2 DIABETES - \"CHANGE\" STUDY\n\nI.A. RATIONALE The investigators will test the hypothesis that maintenance of normoglycemia can prevent the typical worsening of hyperglycemia in early type 2 diabetes (DM) compared to usual care.\n\nProgression of hyperglycemia is mediated by loss of β-cell function, which will be mitigated by normalizing glucose levels, reducing the \"excitotoxicity\" leading to dedifferentiation and apoptosis. When lifestyle change or Rx reduced progression from prediabetes (PreDM) to DM, there was no \"catch-up\" after trials ended - cumulative DM remained less than in controls, consistent with a change in the natural history. Reaching normal glucose is beneficial regardless of the intervention: in the Diabetes Prevention Program (DPP), PreDM subjects who achieved normal glucose levels only once, had 56% less DM in the DPP Outcomes Study \\[DPPOS\\] - similar in lifestyle change, metformin, and control groups. But if treatment is begun too late, even 10 kg weight loss may not lead to DM remission.\n\nI.B. FEATURES OF THE APPROACH - easy to translate into practice.\n\nThis study will be novel: 1) Aim for normal glucose, instead of testing Rx or mechanisms \\[as in STOP DIABETES, DPP, and RISE\\], since lowering glucose per se improves β-cell function. 2) Start early in the natural history, instead of late \\[as in ACCORD, ADVANCE, and VADT\\], allowing use of Rx with a low risk of hypoglycemia; severe hypoglycemia was unusual in ORIGIN, where DM duration was only 5.5 years. 3) Target early DM instead of PreDM \\[DREAM, DPP, ACT NOW, and STOP DIABETES\\], allowing use of Rx FDA approved for DM. 4) Accelerated stepped intensification of Rx to keep glucose normal, vs. \\< 10% reaching a normal OGTT 3 times in the DPP, only 15% reaching a normal OGTT with metformin over 2 years in RISE, and lack of normalization in other studies.\n\nI.C. AIMS - assess effect size, β-cell function, retinopathy, nephropathy, CGM, cost-effectiveness.\n\nMethods: To ensure separation of treatment arms, the investigators will study DM expected to progress. 126 adults will be randomized to ensure that 102 complete the study, allowing for dropouts, 1/3 in each of 3 groups: (i) A1c 6.0-6.9%, no Rx; (ii) A1c 6.0-6.9%, on metformin; (iii) A1c 7.0-7.4%, on metformin. All will have DM by OGTT + 1 hour OGTT glucose ≥155 mg/dl to increase the risk of progression. After a 2-week run-in to establish tolerance to metformin (if not on it already) and adherence to self-monitoring of blood glucose (SMBG), all will have a lifestyle intervention \\[VA MOVE!, similar to the DPP\\], and HbA1c and 2 weeks of continuous glucose monitoring (Abbott CGM) every 3 months. Randomization will be 1:1 within each group, to intensive Rx: adding Rx if SMBG levels are \\> goal (\\<100 mg/dl premeal and \\<130 postmeal) ≥3x/week 2 weeks in a row after ≥4 weeks of maximum tolerated dosage (MTD) of Rx; metformin (if not on it already), + TZD pioglitazone, + GLP-1 RA semaglutide, + SGLT-2 empagliflozin, + glargine insulin; or control Rx: adding Rx in the same order, based on HbA1c every 3 months; initial added Rx for HbA1c ≥7.0%, subsequent Rx for HbA1c ≥7.5% \\[similar to use in GRADE and typical VA practice\\].\n\nOutcomes: Over 2.5 years, plus a 3-month washout, the investigators will quantitate (i) effect size - differences in HbA1c with intensive Rx vs. controls - from the Rx paradigm, expected to be 5.2-5.6% vs. 6.5-7.4%, respectively; and (ii) β-cell function \\[in 3-hour OGTTs with modeling as in RISE\\], since trends with intensive vs. control Rx post-washout may indicate whether β-cell function is likely to be sustained, consistent with the conclusions of the RISE Consortium. The investigators will also explore (iii) retinopathy (blinded evaluation of fundus photographs); (iv) nephropathy (microalbuminuria and eGFR); (v) whether CGM after ≥3 weeks of MTD could be substituted for SMBG in identifying need for intensification, and (vi) cost-effectiveness.\n\nI.D. HYPOTHESIZED CLINICAL IMPACT OF EARLY DIAGNOSIS AND KEEPING GLUCOSE NORMAL:\n\nEvidence from DM prevention and intervention studies allows us to predict that keeping glucose normal will be safe - and longterm benefits will include reduced complications, mortality, and costs.\n\nII. SIGNIFICANCE\n\nIf a definitive trial demonstrates that keeping glucose normal sustains β-cell function, a change in practice to include this model of intensive Rx should improve both health, and healthcare system resource use and costs. The next step would be to plan a study of impact on renal and retinal outcomes - since lifestyle interventions are now widespread, the Rx classes used have a low risk of hypoglycemia and are going off patent, and this experience in overcoming clinical inertia should facilitate implementation.\n\nIII. EXPERIMENTAL PLAN\n\nThe investigators have a simple design; instead of mechanisms such as insulin action and secretion, eligibility, screening, and interventions will be based only on glucose and HbA1c, to facilitate translation to routine clinical practice. The goals are to (i) establish effect size (differences in HbA1c), (ii) determine if β cell function can be sustained, and (iii) explore retinopathy, nephropathy, cost effectiveness, and potential substitution of CGM for SMBG, to help define the sample size for a subsequent multicenter study.\n\nIV. INTERVENTIONS\n\nIV.A. LIFESTYLE CHANGE SUPPORT - FOR ALL PARTICIPANTS\n\nThe VA's \"MOVE!\" group lifestyle change program is modeled after the DPP, with similar goals - 7% weight loss for those with BMI \\>25, and \\>150 minutes a week of exercise. Other recommendations to PCPs will be per ADA DM guidelines, similar to the VADT - BP, lipid control, etc.\n\nIV.B. CONTROL Rx - INTENSIFICATION BASED ON HbA1c LEVELS, DETERMINED EVERY 3 MONTHS (see below).\n\nIV.C. INTENSIVE Rx - INTENSIFICATION BASED ON SMBG, DONE AN AVERAGE OF ONCE A DAY (see below).\n\nV. POTENTIAL IMPACT ON CLINICAL PRACTICE\n\nThis study (and a follow-up multicenter study) are aimed to change medical practice. If the studies are positive as expected, screening to find early DM, and management aimed at normal glucose, should become routine. Moreover, since hyperglycemia in usual care reaches HbA1c levels much higher than in controls \\[insulin is frequently begun when HbA1c is \\>9%\\], the real-world difference from intensive Rx \\[HbA1c 5.2-5.6%\\] would be correspondingly greater, with a greater impact on health, resource use, and costs. Years of lower glucose, through \"legacy effects\", should reduce DM complications and costs, particularly in high-risk groups - with potential benefit to individuals, health care systems, and society.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Type 2 Diabetes"],"keywords":[],"conditionGroups":[{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"Foundation for Atlanta Veterans Education and Research, Inc.","slug":"foundation-for-atlanta-veterans-education-and-research-inc","class":"OTHER"},"collaborators":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","slug":"national-institute-of-diabetes-and-digestive-and-kidney-diseases-niddk","class":"NIH"},{"name":"Emory University","slug":"emory-university","class":"OTHER"},{"name":"Abbott Diabetes Care","slug":"abbott-diabetes-care","class":"INDUSTRY"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":127,"dates":{"start":"2021-09-01","primaryCompletion":"2027-04-30","completion":"2027-12-31","firstPosted":"2021-09-10","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Atlanta VA Medical Center","status":null,"city":"Decatur","state":"Georgia","country":"United States","latitude":33.77483,"longitude":-84.29631}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* diagnosis of diabetes by OGTT\n* age 40-75 years\n* HbA1c 6.0-7.4%\n* 1 hr OGTT glucose \\>155 mg/dl in each group\n\nExclusion Criteria:\n\n* CVD event during the previous year\n* systemic glucocorticoids\n* bariatric surgery\n* stage III-IV congestive heart failure\n* severe angina\n* life expectancy \\<5 years\n* BMI \\>40 kg/m2\n* pregnancy\n* pancreatitis\n* family or personal history of multiple endocrine neoplasia 2a\n* an estimated glomerular filtration rate \\[eGFR\\] of ≤50 ml/min\n* an alanine aminotransferase (ALT) level \\>3x the upper limit of the normal range\n* dementia","minimumAge":"40 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"OTHER","name":"Intensification of diabetes medication based largely on HbA1c levels","description":"Use of diabetes Rx in controls will be guided largely by HbA1c levels."},{"type":"OTHER","name":"Intensification of diabetes medication based on glucose levels","description":"Use of diabetes Rx in the intensive Rx groups will be guided by participants' self-monitored blood glucose levels (SMBG), with management aimed to keep glucose levels within the normal range."}],"primaryOutcomes":[{"measure":"EFFECT SIZE","description":"HbA1c DIFFERENCEs, INTENSIVE Rx vs. CONTROLS - PRIMARY OUTCOME #1","timeFrame":"2.75 years (includes 3 month washout)"},{"measure":"β-CELL FUNCTION - PRIMARY OUTCOME #2a","description":"β-cell function from modeling using a 3-hour OGTT with samples for glucose, insulin and C-peptide at 10, -5, 10, 20, 30, 60, 90, 120, 150 and 180 minutes.","timeFrame":"2.75 years (includes 3 month washout)"},{"measure":"β-CELL FUNCTION - PRIMARY OUTCOME #2b","description":"β-cell function and insulin sensitivity as the oral \"OGTT ISI disposition index\" (DI), using the \"insulinogenic index\" \\[(Δ insulin/Δ glucose) with 0- and 30-minute insulin (and C-peptide) and glucose levels in the OGTT\\] for insulin secretion and \\[1/(fasting insulin concentration)\\] for insulin action.","timeFrame":"2.75 years (includes 3 month washout)"},{"measure":"β-CELL FUNCTION - PRIMARY OUTCOME #2c.","description":"β-cell function as the 1 hour OGTT plasma glucose (1hrOGTT).","timeFrame":"2.75 years (includes 3 month washout)"}],"secondaryOutcomes":[{"measure":"RETINOPATHY determined by fundus photographs","description":"Assessed with fundus photos graded by readers masked to study groups. The University of Wisconsin Fundus Photograph Reading Center (FPRC) is grading photos for the DPPOS. Under Co-I Dr. Maa's direction, and with dilation, 4 sets of stereo ETDRS-level photos with 45° fields will be taken with a Zeiss Cirrus 600 camera by FPRC-certified VA technologists. Deidentified images will be uploaded via secure OneDrive, and accessed by the FPRC.","timeFrame":"2.5 years"},{"measure":"NEPHROPATHY by eGFR","description":"The development of nephropathy will be assessed with the eGFR according to the CKD-EPI equation, measured in the Atlanta VA Clinical Laboratory, in samples obtained at baseline, and every 6 months through 2.5 years.","timeFrame":"2.5 years"},{"measure":"NEPHROPATHY by urine microalbumin/creatinine ratio","description":"The development of nephropathy will be assessed with the urine microalbumin/creatinine ratio, measured in the Atlanta VA Clinical Laboratory, in samples obtained at baseline, and every 6 months through 2.5 years.","timeFrame":"2.5 years"},{"measure":"Point of care glucose by continuous glucose monitoring (CGM)","description":"After 3 weeks of MOVE! and maximum tolerated dosage of each Rx in intensive Rx subjects, 14 days of CGM will permit ROC analysis to compare AG vs. SMBG in predicting need for more Rx, and use of the Youden index to define an optimal glucose cutoff. We will also assess prediction of needing the first vs. later Rx; ROC areas should be independent of disease prevalence.","timeFrame":"2.5 years"},{"measure":"COST EFFECTIVENESS - to be explored only if additional (ancillary) funding can be obtained","description":"We will use a microsimulation model to extrapolate the glycemic reduction with intensive Rx observed in the trial to the potential reduction in DM complications and related costs in a lifetime window.","timeFrame":"2.5 years"}],"publications":[{"pmid":"25249668","citation":"Phillips LS, Ratner RE, Buse JB, Kahn SE. We can change the natural history of type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2668-76. doi: 10.2337/dc14-0817."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05040087"},{"nctId":"NCT05313529","title":"LIGHT-MCI Trial: GLP-1 Agonist, SGLT2 Inhibitor, and DPP-4 Inhibitor for MCI Remission in Type 2 Diabetes","officialTitle":"Effects of Liraglutide, Empagliflozin and Linagliptin on Mild Cognitive Impairment Remission in Type 2 Diabetes (LIGHT-MCI): A Multicentre, Randomised Controlled Trial With An Extension Phase","summary":"This is an investigator-led prospective, randomized, open label, parallel study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the cognitive function in T2DM patients with mild cognitive impairment (MCI), consisting of a 48-week core study followed by a 28-week extension phase.","detailedDescription":"The LIGHT-MCI trial is an investigator-led, prospective, randomized, open label, parallel, multi-center study to explore and evaluate the therapeutic effects of Liraglutide, Empagliflozin and Linagliptin on the MCI remission in T2DM patients with MCI inadequately controlled with metformin monotherapy. The trial consists of a 48-week core study followed by an extension phase through to 76 weeks and the investigators will screen in the outpatient and inpatient departments to enroll 396 patients (132 for each arm) totally with the inclusion and exclusion criteria. The patients will be randomized at a 1:1:1 ratio into Liraglutide, Empagliflozin and Linagliptin treatment group with a computer-generated random order. All patients will also continue on their existing dose and regimen of metformin throughout the study. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, body composition analysis, cognitive assessment, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all patients. During the treatment period, visits at 8-week intervals will be performed to evaluate the safety of drugs and adjust the dose of metformin if hypoglycaemia occurs; meanwhile, fasting and 2-hour postprandial plasma glucose assayed by fingerstick, physical examination, and olfactory test will be conducted. Participants who complete the 48-week core study will have the option to receive an additional 28 weeks of intervention after signing an extension consent form. At 48 and 76 weeks of treatment, all of the assessments will be performed again for all recruited subjects, including early withdrawal patients.","peptideSlugs":["liraglutide","glucagon"],"peptideNames":["Liraglutide","Glucagon"],"conditions":["Type 2 Diabetes Mellitus","Mild Cognitive Impairment"],"keywords":["Functional MRI","cognition","Olfactory function","Liraglutide, Empagliflozin and Linagliptin"],"conditionGroups":[{"slug":"type-2-diabetes","label":"Type 2 diabetes"},{"slug":"brain-health","label":"Brain health"}],"sponsor":{"name":"The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School","slug":"the-affiliated-nanjing-drum-tower-hospital-of-nanjing-university-medical-school","class":"OTHER"},"collaborators":[{"name":"Nanjing First Hospital, Nanjing Medical University","slug":"nanjing-first-hospital-nanjing-medical-university","class":"OTHER"},{"name":"The Affiliated Jiangning Hospital of Nanjing Medical University","slug":"the-affiliated-jiangning-hospital-of-nanjing-medical-university","class":"OTHER"},{"name":"Wuxi People's Hospital","slug":"wuxi-people-s-hospital","class":"OTHER"},{"name":"Changzhou No.2 People's Hospital","slug":"changzhou-no-2-people-s-hospital","class":"OTHER"}],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":396,"dates":{"start":"2022-10-08","primaryCompletion":"2025-12-31","completion":"2026-07-01","firstPosted":"2022-04-06","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":5,"countries":["China"],"locations":[{"facility":"Department of Endocrinology, Changzhou No.2 People's Hospital, the Affiliated Hospital of Nanjing Medical University","status":null,"city":"Changzhou","state":"Jiangsu","country":"China","latitude":31.77359,"longitude":119.95401},{"facility":"Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University","status":null,"city":"Nanjing","state":"Jiangsu","country":"China","latitude":32.06167,"longitude":118.77778},{"facility":"Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School","status":null,"city":"Nanjing","state":"Jiangsu","country":"China","latitude":32.06167,"longitude":118.77778},{"facility":"Department of Endocrinology, the Affiliated Jiangning Hospital of Nanjing Medical University","status":null,"city":"Nanjing","state":"Jiangsu","country":"China","latitude":32.06167,"longitude":118.77778},{"facility":"Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University","status":null,"city":"Wuxi","state":"Jiangsu","country":"China","latitude":31.56887,"longitude":120.28857}],"eligibility":{"criteria":"Inclusion criteria\n\n1. Participants aged ≥40 and ≤75 years, of any gender.\n2. Type 2 diabetes diagnosed according to the American Diabetes Association criteria\n3. Mild cognitive impairment diagnosed according to the established criteria\n\n   1. Cognitive concern from the patient, or an informant or skilled clinicians\n   2. Objective evidence of cognitive impairment: education-adjusted MoCA score ≤ 25 and ≥ 18; or ≥1.0 standard deviation below the mean of age- and education-specific groups on any cognitive subdomain\n   3. Preservation of independence in daily living abilities: Barthel Index score ≥ 60\n   4. Absence of dementia\n4. Treatment with a stable glucose lowering regimen of metformin monotherapy (≥ 1,000 mg daily) or combination with sulfonylurea/glibenclamide/glycosidase inhibitor/basal insulin over the previous 3 months\n5. Glycosylated hemoglobin (HbA1c) during screening between ≥7.0% and ≤10.0%\n6. BMI of ≥ 19 kg/m2\n7. Education duration of ≥6 years\n8. Right-handed participants\n9. Understanding of the research procedures and methods, potential benefits and risks of the trial, and sign written informed consent\n\nExclusion criteria\n\n1. History of other dementia-related neurological diseases, depression within the past 2 years, developmental disorders, mania, depression, schizophrenia, etc.\n2. Significant nasal sinusitis, nasal cavity and sinus polyps, cranial or nasopharyngeal tumors and other space-occupying lesions, congenital diseases and trauma of the nose, maxillofacial area, and skull base that affect olfaction. Symptoms of upper respiratory tract infection on the day of MRI examination, including nasal congestion, rhinorrhea, fever, etc.\n3. Acute metabolic complications such as diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemic coma within the previous 6 months\n4. Severe organ dysfunction of heart, liver, kidneys, and thyroid, including unstable angina, myocardial infarction, or grade II and above cardiac insufficiency within 3 months before screening; estimated glomerular filtration rate (eGFR) by CKD-EPI formula \\&lt;45 mL/min/1.73 m², alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater exceeding twice the upper limit of normal, hyperthyroidism or uncontrolled hypothyroidism\n5. History of medullary thyroid carcinoma, pancreatitis, multiple endocrine neoplasia syndrome type 2, recurrent urinary tract infections, severe gastrointestinal diseases or history of gastrointestinal surgery, history of malignant tumors\n6. With MRI contraindications, such as implanted metal prosthesis, claustrophobia, etc.\n7. Females who are pregnant, lactating, breast feeding or of child bearing age without effective contraception\n8. Participated in other clinical trials within the previous 6 months\n9. Known or suspected allergy to the study drugs\n10. Received treatment with GLP-1RAs, dual GLP-1R/GCGR agonist, SGLT-2 inhibitors or DPP4 inhibitors in the past 3 months\n11. Known history of drug or alcohol abuse within the past 6 months","minimumAge":"40 Years","maximumAge":"75 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Liraglutide","description":"Liraglutide will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study"},{"type":"DRUG","name":"Empagliflozin","description":"Empagliflozin will be initiated and maintained at 10mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study."},{"type":"DRUG","name":"Linagliptin","description":"Iinagliptin will be initiated at 5mg/ day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study."}],"primaryOutcomes":[{"measure":"Mild cognitive impairment (MCI) remission rate","description":"MCI mitigation is defined by three criteria: an education-adjusted score of the Montreal Cognitive Assessment (MoCA) ≥26, no cognitive deficits in any explored cognitive subdomain, including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory, evaluated by Trail-Making Test, Stroop Color-Word Test and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively, and preservation of ability to perform instrumental activity of daily living (IADL) with a Functional Activities Questionnaire (FAQ) score \\<5.","timeFrame":"The core study spans from baseline to 48 weeks"}],"secondaryOutcomes":[{"measure":"Change in score of Mini-Mental State Examination (MMSE)","description":"The MMSE contains a total of 30 items that assess orientation, registration, attention and calculation, recall, and language, with a score range from 0 to 30. Generally, a higher MMSE score reflects a better cognitive function.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Changes in score of MoCA","description":"The MoCA (Chinese version) is a screening instrument for MCI comprised of 30 items to assess multiple cognitive domains (memory recall, visuospatial abilities, executive functions, attention, language, and orientation to time and place; scores range from 0 to 30, with higher scores indicating better cognitive function). Participants received one additional point if they had a MoCA score \\< 30 and 12 years or less of formal school education.","timeFrame":"from baseline to weeks 24, 48, and 76 of treatment (the core study spans from baseline to 24, and 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Changes in total score of RBANS","description":"The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data, which consists of 12 task tests assessing 5 cognitive domains, namely immediate memory, visuospatial/ constructional, language, attention and delayed memory, with a score range from 40 to 160. A higher RBANS score reflects a better global cognitive function.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in the RBANS index score of immediate memory","description":"The RBANS (Chinese version) is a brief neuropsychological screening battery with established test-retest reliability and age-appropriate normative data. The RBANS includes 12 sub-tests that generate five age-adjusted index scores and a total score. The five indices include immediate memory (consisting of list learning and story memory tests), visuospatial/constructional domain (consisting of figure copying and line orientation tests), language (consisting of picture naming and semantic fluency tests), attention (consisting of digit span and coding tests) and delayed memory (consisting of list recall, story recall, figure recall and list recognition tests). Generally, a higher index score reflects a better cognitive subdomain function.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in the RBANS index score of visuospatial/constructional","description":"Measurements and instruments are the same as the RBANS index score of immediate memory.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in the RBANS index score of language","description":"Measurements and instruments are the same as the RBANS index score of immediate memory.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in the RBANS index score of attention","description":"Measurements and instruments are the same as the RBANS index score of immediate memory.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in the RBANS index score of delayed memory","description":"Measurements and instruments are the same as the RBANS index score of immediate memory.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in aggregate time to test completion for Trail Making Test (TMT)","description":"The TMT is a validated timed measure of processing speed, which consists of part A and part B (TMT-A and TMT-B). The time limits for performing the TMT-A and TMT-B are 180 and 300 seconds, respectively. Processing speed is estimated by the aggregate time in seconds to complete TMT-A and TMT-B such that less time indicate faster processing speed.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."},{"measure":"Change in aggregate time to test completion for Victoria Stroop Color-Word Test","description":"The Victoria Stroop Color-Word Test is a well-known measure of executive function. There are three indices including Stroop-dot, Stroop-word and Stroop-color word in the test. The color task consists of colored dots; the word task comprises ordinary words that are unrelated to the meaning of color; the color-word task consists of words written in color that indicate the meaning of the color, but the color of these words differs from the meaning of the word itself. The participants were asked to quickly read the color of the dots or Chinese words on the cards. The sum of consuming time taken to read the three cards is used as an index of executive function performance. Less time indicates better executive function.","timeFrame":"from baseline to week 48, and 76 of treatment (the core study spans from baseline to 48 weeks, and the week 76 assessment will be analyzed and reported after the extension phase)."}],"publications":[{"pmid":"31221697","citation":"Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21."},{"pmid":"29500313","citation":"Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2."},{"pmid":"35263425","citation":"Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064."},{"pmid":"40840993","citation":"Yu C, Yang H, Zhang B, Chen S, Yang S, Li F, Zhu W, Zhai B, Wu T, Zhao S, Zhang W, Tong X, Duan Y, Zhang L, Chao Y, Wu J, Zhu X, Wang K, Ye X, Zhang X, Xu X, Cheng H, Liu J, Zhang J, Wang Y, Zhang Z, Yan W, Bi Y. Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase. BMJ Open. 2025 Aug 21;15(8):e095382. doi: 10.1136/bmjopen-2024-095382."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05313529"},{"nctId":"NCT06077864","title":"A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Obesity (SYNCHRONIZE™ - CVOT)","officialTitle":"A Phase 3, Randomised, Double-blind, Parallel-group, Event-driven, Cardiovascular Safety Study With BI 456906 Administered Subcutaneously Compared With Placebo in Participants With Overweight or Obesity With Established Cardiovascular Disease (CVD) or Chronic Kidney Disease, and/or at Least Two Weight-related Complications or Risk Factors for CVD","summary":"This study is open to adults who are at least 18 years old and have a body mass index (BMI) of 27 kg/m2 or more. People can take part if they have cardiovascular or chronic kidney disease. People who have at least 2 health problems related to their weight or risks of cardiovascular disease can participate. Participants must have previously tried to lose weight by changing their diet.\n\nThe purpose of this study is to find out whether people with overweight or obesity who take a medicine called survodutide (BI 456906) are less or more likely to develop serious cardiovascular problems. It also aims to find out whether health parameters like blood pressure improve. Overweight and obesity are linked to cardiovascular disease. Survodutide is a medicine that is developed to help people with obesity or overweight to lose weight.\n\nParticipants are divided into 3 groups of almost equal size. 2 groups get different doses of survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Every participant has a 2 in 3 chance of getting survodutide. Participants inject survodutide or placebo under the skin once a week. All participants also receive counselling on diet and physical activity.\n\nParticipants are in the study for up to 2 years and 3 months. During this time, it is planned that participants visit the study site up to 21 times and attend remote visits by video calls. During these visits, the doctors check participants' cardiovascular and overall health. The results are compared between survodutide and placebo groups. The study staff also takes note of any unwanted effects.","detailedDescription":null,"peptideSlugs":["survodutide"],"peptideNames":["Survodutide"],"conditions":["Obesity"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Boehringer Ingelheim","slug":"boehringer-ingelheim","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":5531,"dates":{"start":"2023-11-20","primaryCompletion":"2026-06-01","completion":"2026-06-30","firstPosted":"2023-10-11","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":540,"countries":["Argentina","Australia","Austria","Belgium","Brazil","Bulgaria","Canada","China","Czechia","Denmark","Finland","Germany","Greece","Hong Kong","Hungary","India","Ireland","Italy","Japan","Kazakhstan","Mexico","Netherlands","New Zealand","Norway","Poland","Portugal","Puerto Rico","Saudi Arabia","Slovakia","South Korea","Spain","Taiwan","Turkey (Türkiye)","United Kingdom","United States"],"locations":[{"facility":"Cardiology P.C.","status":null,"city":"Birmingham","state":"Alabama","country":"United States","latitude":33.52066,"longitude":-86.80249},{"facility":"AMR Daphne","status":null,"city":"Daphne","state":"Alabama","country":"United States","latitude":30.60353,"longitude":-87.9036},{"facility":"AMR Mobile","status":null,"city":"Mobile","state":"Alabama","country":"United States","latitude":30.69436,"longitude":-88.04305},{"facility":"Mobile Heart Specialists, PC","status":null,"city":"Mobile","state":"Alabama","country":"United States","latitude":30.69436,"longitude":-88.04305},{"facility":"The Institute for Liver Health II DBA Arizona Clinical Trials","status":null,"city":"Chandler","state":"Arizona","country":"United States","latitude":33.30616,"longitude":-111.84125},{"facility":"Clinical Research Institute of Arizona, LLC","status":null,"city":"Sun City West","state":"Arizona","country":"United States","latitude":33.66198,"longitude":-112.34127},{"facility":"AMR Phoenix","status":null,"city":"Tempe","state":"Arizona","country":"United States","latitude":33.41477,"longitude":-111.90931},{"facility":"Arizona Liver Health-Tucson-67516","status":null,"city":"Tucson","state":"Arizona","country":"United States","latitude":32.22174,"longitude":-110.92648},{"facility":"Yuma Clinical Trials","status":null,"city":"Yuma","state":"Arizona","country":"United States","latitude":32.72532,"longitude":-114.6244},{"facility":"Lynn Institute of the Ozarks","status":null,"city":"Little Rock","state":"Arkansas","country":"United States","latitude":34.74648,"longitude":-92.28959},{"facility":"Velocity Clinical Research-Huntington Park","status":null,"city":"Huntington Park","state":"California","country":"United States","latitude":33.98168,"longitude":-118.22507},{"facility":"Velocity Clinical Research, San Diego","status":null,"city":"La Mesa","state":"California","country":"United States","latitude":32.76783,"longitude":-117.02308},{"facility":"Velocity Clinical Research - Los Angeles","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Catalina Research Institute, LLC","status":null,"city":"Montclair","state":"California","country":"United States","latitude":34.07751,"longitude":-117.68978},{"facility":"Valley Clinical Trials, Inc.","status":null,"city":"Northridge","state":"California","country":"United States","latitude":34.22834,"longitude":-118.53675},{"facility":"NorCal Endocrinology and Internal Medicine","status":null,"city":"San Ramon","state":"California","country":"United States","latitude":37.77993,"longitude":-121.97802},{"facility":"Velocity Clinical Research, Santa Ana","status":null,"city":"Santa Ana","state":"California","country":"United States","latitude":33.74557,"longitude":-117.86783},{"facility":"NorthBay Clinical Research, LLC","status":null,"city":"Santa Rosa","state":"California","country":"United States","latitude":38.44047,"longitude":-122.71443},{"facility":"Velocity Clinical Research-Van Nuys-70286","status":null,"city":"Van Nuys","state":"California","country":"United States","latitude":34.18667,"longitude":-118.44897},{"facility":"Peak Gastroenterology Associates-Colorado Springs-62256","status":null,"city":"Colorado Springs","state":"Colorado","country":"United States","latitude":38.83388,"longitude":-104.82136},{"facility":"Bridgeport Hospital","status":null,"city":"Bridgeport","state":"Connecticut","country":"United States","latitude":41.17923,"longitude":-73.18945},{"facility":"CMR of Greater New Haven, LLC","status":null,"city":"Hamden","state":"Connecticut","country":"United States","latitude":41.39593,"longitude":-72.89677},{"facility":"Chase Medical Research, LLC","status":null,"city":"Waterbury","state":"Connecticut","country":"United States","latitude":41.55815,"longitude":-73.0515},{"facility":"Proactive Clinical Research","status":null,"city":"Boca Raton","state":"Florida","country":"United States","latitude":26.35869,"longitude":-80.0831}],"eligibility":{"criteria":"Inclusion Criteria:\n\n1. Male or female, age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is \\>18 years.\n2. Body mass index (BMI) ≥27 kg/m2 at screening with established cardiovascular disease (CVD) and/or at least 2 weight-related complications or risk factors for CVD OR BMI ≥30 kg/m2 at screening with established CVD or chronic kidney disease (CKD), and/or at least 2 weight-related complications or risk factors for CVD.\n\nFurther inclusion criteria apply.\n\nExclusion criteria:\n\n1. Previous treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists within 3 months before screening.\n2. Type 1 diabetes.\n3. Less than 3 months between the last dose of GLP-1R agonists and GLP-1R agonist/insulin/glucose-dependent insulinotropic polypeptide (GIP) combinations and screening.\n4. Known clinically significant gastric emptying abnormality (e.g., severe diabetic gastroparesis or gastric outlet obstruction).\n\nFurther exclusion criteria apply.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"COMBINATION_PRODUCT","name":"survodutide","description":"once weekly subcutaneous injection, pre-filled syringe"},{"type":"COMBINATION_PRODUCT","name":"Placebo","description":"once weekly subcutaneous injection, pre-filled syringe"}],"primaryOutcomes":[{"measure":"Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (to demonstrate non-inferiority)","description":"Heart failure events (HFE) includes hospitalisation for heart failure (HHF), emergency room visit, urgent care visit, or urgent outpatient heart failure (HF) visit (5-point major adverse cardiac event (5P-MACE)) CV-Cardiovascular MI-Myocardial infarction","timeFrame":"up to Week 114"}],"secondaryOutcomes":[{"measure":"Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3-point major adverse cardiac event (3P-MACE)) (to demonstrate non-inferiority)","description":null,"timeFrame":"up to Week 114"},{"measure":"Absolute change in systolic blood pressure (SBP) (mmHg) from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in waist circumference (cm) from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) from baseline to Week 72 in trial participants with HF at baseline","description":"KCCQ-TSCC scale score range is from 0 to 100 where low score means patient not doing well and higher score means patient doing better.","timeFrame":"At Baseline and at Week 72"},{"measure":"Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (to demonstrate superiority)","description":null,"timeFrame":"up to Week 114"},{"measure":"Percentage change in body weight from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in diastolic blood pressure (DBP) (mmHg) from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in aspartate aminotransferase (AST) (U/L) from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in alanine aminotransferase (ALT) (U/L) from baseline to Week 72","description":null,"timeFrame":"Baseline and at Week 72"},{"measure":"Absolute change in glycosylated haemoglobin A1c (HbA1c) (mmol/mol) from baseline to Week 72 in trial participants with type 2 diabetes mellitus (T2DM)","description":null,"timeFrame":"Baseline and at Week 72"}],"publications":[{"pmid":"39453356","citation":"Kosiborod MN, Platz E, Wharton S, le Roux CW, Brueckmann M, Ajaz Hussain S, Unseld A, Startseva E, Kaplan LM; SYNCHRONIZE-CVOT Trial Committees and Investigators. Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial. JACC Heart Fail. 2024 Dec;12(12):2101-2109. doi: 10.1016/j.jchf.2024.09.004. Epub 2024 Oct 23."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06077864"},{"nctId":"NCT06523530","title":"Effect of a GnRH Analog on Hepatic Steatosis","officialTitle":"Effect of the Pharmacological Cessation of Menstruation With a GnRH Analog on Hepatic Steatosis in Women With Endometriosis","summary":"Menopause increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), possibly owing to the abrupt lack of estrogen. Gonadotropin-releasing hormone (GnRH) treatment in endometriosis is regarded as a model of pharmaceutical menopause. Thus, the effect of goserelin acetate, a GnRH analog that results in transient menopause, on hepatic steatosis and fibrosis will be evaluated in this study.","detailedDescription":"The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which until recently was known as nonalcoholic fatty liver disease (NAFLD), has risen to 30% of the global adult general population, whereas the pharmaceutical interventions against it remain limited. Owing to the epidemiologic and pathophysiologic association of MASLD with obesity, type 2 diabetes mellitus, dyslipidemia and arterial hypertension, the diagnostic criteria for MASLD are similar to those of the metabolic syndrome.\n\nMenopause has been associated with higher MASLD prevalence, with the lack of estrogen being a very plausible pathogenetic contributor to this liver disease. Other pathogenetic contributors of MASLD, including abdominal obesity, increase in insulin resistance (IR) and dysmetabolism of carbohydrates and lipids, are aggravated after menopause, thus adversely contributing to the pathogenesis of MASLD. Regarding the effect of the lack of estrogen on the liver, most to date data are derived from experimental studies, largely showing a favoring effect on MASLD. Epidemiological studies have also shown menopause as an associate of MASLD. However, existing clinical studies are mostly observational, thereby not being able to show a causative association between menopause and MASLD.\n\nGonadotropin-releasing hormone (GnRH) treatment in disorders such as endometriosis can be regarded as a model of pharmaceutical menopause. More specifically, GnRH analogs, like goserelin acetate, lead to pharmaceutical menopause by suppressing the axis hypothalamus-pituitary-ovaries, thus, causing an iatrogenic, reversible ovarian cessation, which lasts as long as the use of GnRH. The adverse effects of GnRH are generally mild and reversible after their discontinuation.\n\nThis is a prospective, interventional non-randomized study, which aims to evaluate the effect of goserelin acetate on hepatic steatosis in women with histologically confirmed endometriosis compared with women with endometriosis that will not receive pharmacological treatment post-surgically.","peptideSlugs":["goserelin"],"peptideNames":["Goserelin"],"conditions":["Metabolic Dysfunction-Associated Steatotic Liver Disease","Nonalcoholic Fatty Liver","Endometriosis"],"keywords":["endometriosis","goserelin acetate","hepatic fibrosis","MASLD","MASH","metabolic dysfunction-associated steatotic liver disease","metabolic dysfunction-associated steatohepatitis","NAFLD","NASH","nonalcoholic fatty liver disease","nonalcoholic steatohepatitis","treatment","menopause"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Aristotle University Of Thessaloniki","slug":"aristotle-university-of-thessaloniki","class":"OTHER"},"collaborators":[{"name":"424 General Military Hospital","slug":"424-general-military-hospital","class":"OTHER"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":62,"dates":{"start":"2024-11-26","primaryCompletion":"2027-04","completion":"2027-10","firstPosted":"2024-07-26","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":2,"countries":["Greece"],"locations":[{"facility":"424 General Military Hospital","status":null,"city":"Thessaloniki","state":"Thessaloniki","country":"Greece","latitude":40.64072,"longitude":22.93493},{"facility":"1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki","status":null,"city":"Thessaloniki","state":null,"country":"Greece","latitude":40.64072,"longitude":22.93493}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* women of reproductive age\n* diagnosis of endometriosis. The disease is suspected by patient's individual history (chronic pelvic pain, dyspareunia or/and dysmenorrhea) and the ultrasonographic imaging (chocolate cysts). The diagnosis is confirmed histologically, after laparoscopic surgical treatment and biopsy sampling, which will be interpreted by an independent blinded pathologist.\n* use of contraceptives, which is the first line treatment, is contraindicated or the patient does not consent to receive contraceptives, due to personal preferences.\n* written informed consent to participate to the study\n\nExclusion Criteria:\n\n* mean ethanol consumption \\>10 g/day\n* history of other chronic liver disease (e.g., viral hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and overlap syndromes, drug-induced liver injury, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)\n* liver cirrhosis\n* any malignancy\n* chronic kidney disease\n* uncontrolled hypothyroidism or hyperthyroidism\n* severe sexual hormone disorders (congenital adrenaline hyperplasia, Down syndrome, Turner syndrome).\n* use of the following medications within a 12-month period before baseline, which are associated with drug-induced liver injury (DILI): interferon, tamoxifen, amiodarone, aloperidin, glucocorticoids, hormone replacement therapy, contraceptives, anabolic steroids, any medication against tuberculosis, epilepsy or viruses, methotrexate, parenteral nutrition\n* use of the following medications within a 12-month period before baseline, which are probably associated with improvement in hepatic steatosis: vitamin E, pioglitazone, insulin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium- glucose co-transporter-2 inhibitors (SGLT-2i), orlistat, ursodeoxycholic acid\n* use of any GnRH agonist or antagonist within a 12-month period before baseline","minimumAge":"18 Years","maximumAge":"45 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Goserelin Acetate 3.6 mg inj, implant","description":"3.6 mg (1ml) administered subcutaneously once every month for 6 months (totally 6 injections)"}],"primaryOutcomes":[{"measure":"Hepatic steatosis","description":"Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s.\n\nBetween-within group interactions in UGAP\n\nUGAP is a non-invasive index based on the attenuation quantification of the ultrasound beam through the hepatic parenchyma, thus used for hepatic steatosis quantification. Cut-off values of ≥ 0.53 dB/cm/MHz, ≥ 0.60 dB/cm/MHz, and ≥ 0.65 dB/cm/MHz have been proposed for the diagnosis of steatosis grade S1, S2, and S3, respectively","timeFrame":"6 months"},{"measure":"Hepatic fibrosis","description":"Liver stiffness (LS) measured with 2D Shear Wave Elastography (2D SWE) on an ultrasound machine GE Logiq E10s.\n\nBetween-within group interactions in LS\n\n2D SWE is a non-invasive tool measuring the hepatic parenchyma stiffness, thus indirectly suggesting fibrosis stage (F). Cut-offs values of \\<8.27 kPa, 8.27-9.39 kPa, 9.40-11.88 kPa and ≥11.88 kPa have been proposed for F0-F1, F2, F3, and F4, respectively.","timeFrame":"6 months"}],"secondaryOutcomes":[{"measure":"Liver function tests I - ALT and AST","description":"Between-within group interactions will be performed for each of the following parameters:\n\nAlanine aminotransferase (ALT; IU/l), aspartate aminotransferase (AST; IU/l);\n\nALT to AST ratio will be calculated","timeFrame":"6 months"},{"measure":"Liver function tests II - γGT","description":"Between-within group interactions will be performed for:\n\nγ-glutamyltransferase (GGT; IU/l)","timeFrame":"6 months"},{"measure":"Insulin resistance","description":"Between-within group interactions will be performed for Homeostasis Model Assessment - Insulin Resistance (HOMA-IR), which is calculated by the formula: fasting glucose (mg/dl) × insulin (mU/l)/405, and is an index of insulin resistance; higher score indicates greater insulin resistance.","timeFrame":"6 months"},{"measure":"Lipid profile","description":"Between-within group interactions will be performed for each of the following parameters:\n\nTotal cholesterol (TC; mg/dL) Triglycerides (TG; mg/dL) High-density lipoprotein cholesterol (HDL-C; mg/dL) 4. Low-density lipoprotein cholesterol (LDL-C)\n\nLDL-C (mg/dL) is calculated by the formula: TC (mg/dl) - HDL-C (mg/dl) - TG (mg/dl)/5.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis index I - Fatty Liver Index (FLI)","description":"FLI is calculated by the formula \\[(e0.953 × Loge (TG, mg/dL) + 0.139×BMI (kg/m2) + 0.718× Loge (GGT, U/L) + 0.053 × waist circumference (cm) -15.745) / (1 + e0.953 × Loge (TG, mg/dL) + 0.139×BMI (kg/m2) + 0.718×Loge (GGT, U/L) + 0.053 × waist circumference (cm) -15.745)\\] × 100.\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis index II - Hepatic Steatosis Index (HSI)","description":"HSI is calculated by the formula: 8 \\* ALT (U/L) / AST (U/L) + BMI (kg/m2) + 2 \\[if type 2 diabetes melitus (T2DM)\\] + 2 (if female).\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis index III - Triglyceride/Glucose Index (TyG)","description":"TyG is calculated by the formula: Ln\\[TG (mg/dL) \\* Glu (mg/dL) / 2\\].\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis index IV - Tyg-BMI","description":"Tyg-BMI is calculated by the formula: TyG \\* BMI (kg/m2).\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis indices V - NAFLD test","description":"NAFLD test is calculated by the formula: -0.695 + 0.031 \\* BMI (kg/m2) + 0.003 \\* TC (mg/dL) + 0.014 \\* ALT (U/L) + 0.025 \\* C-reactive protein (CRP) (mg/dL).\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"},{"measure":"Non-invasive hepatic steatosis index VI - Metabolic Score for Insulin Resistance (MetS-IR)","description":"MetS-IR is calculated by the formula: Ln\\[2 \\* Glu (mg/dL) + TG (mg/dL)\\] \\* BMI (kg/m2) / Ln\\[HDL-C (mg/dL)\\].\n\nBetween-within group interactions will be performed.","timeFrame":"6 months"}],"publications":[{"pmid":"35880713","citation":"Henry L, Paik J, Younossi ZM. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther. 2022 Sep;56(6):942-956. doi: 10.1111/apt.17158. Epub 2022 Jul 26."},{"pmid":"37363821","citation":"Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966-1986. doi: 10.1097/HEP.0000000000000520. Epub 2023 Jun 24."},{"pmid":"16681555","citation":"Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006 May;23(5):469-80. doi: 10.1111/j.1464-5491.2006.01858.x."},{"pmid":"35532850","citation":"Polyzos SA, Lambrinoudaki I, Goulis DG. Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease. Hormones (Athens). 2022 Sep;21(3):375-381. doi: 10.1007/s42000-022-00369-8. Epub 2022 May 9."},{"pmid":"38760254","citation":"Polyzos SA, Goulis DG. Menopause and metabolic dysfunction-associated steatotic liver disease. Maturitas. 2024 Aug;186:108024. doi: 10.1016/j.maturitas.2024.108024. Epub 2024 May 14."},{"pmid":"29224098","citation":"Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12."},{"pmid":"29992886","citation":"Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol. 2019;17(6):546-555. doi: 10.2174/1570161116666180711121949."},{"pmid":"27225336","citation":"Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016 Sep;42(9):1152-8. doi: 10.1111/jog.13023. Epub 2016 May 26."},{"pmid":"29975553","citation":"Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opin Pharmacother. 2018 Jul;19(10):1109-1125. doi: 10.1080/14656566.2018.1494154. Epub 2018 Jul 5."},{"pmid":"23770813","citation":"DiVasta AD, Laufer MR. The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis. Curr Opin Obstet Gynecol. 2013 Aug;25(4):287-92. doi: 10.1097/GCO.0b013e32836343eb."},{"pmid":"32151660","citation":"Polyzos SA, Kang ES, Boutari C, Rhee EJ, Mantzoros CS. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020 Oct;111S:154203. doi: 10.1016/j.metabol.2020.154203. Epub 2020 Mar 6."},{"pmid":"24121382","citation":"Polyzos SA, Kountouras J, Tsatsoulis A, Zafeiriadou E, Katsiki E, Patsiaoura K, Zavos C, Anastasiadou VV, Slavakis A. Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones (Athens). 2013 Jul-Sep;12(3):405-16. doi: 10.1007/BF03401306."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06523530"},{"nctId":"NCT07035093","title":"A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back Pain","officialTitle":"A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Retatrutide Once Weekly in Participants Who Have Obesity or Overweight and Chronic Low Back Pain","summary":"The main purpose of this study is to evaluate the efficacy and safety of retatrutide in relieving chronic low back pain in participants who have obesity or overweight. Participation in the study will last about 80 weeks.","detailedDescription":null,"peptideSlugs":["retatrutide"],"peptideNames":["Retatrutide"],"conditions":["Obesity","Overweight","Chronic Low Back Pain (CLBP)"],"keywords":["Axial Predominant Low Back Pain"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"pain","label":"Pain"}],"sponsor":{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":586,"dates":{"start":"2025-05-29","primaryCompletion":"2027-09","completion":"2027-09","firstPosted":"2025-06-24","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":40,"countries":["Argentina","Canada","Poland","United States"],"locations":[{"facility":"MD First Research - Chandler","status":null,"city":"Chandler","state":"Arizona","country":"United States","latitude":33.30616,"longitude":-111.84125},{"facility":"Tucson Orthopaedic Institute - North Wyatt Drive","status":null,"city":"Tucson","state":"Arizona","country":"United States","latitude":32.22174,"longitude":-110.92648},{"facility":"Ark Clinical Research - Fountain Valley","status":null,"city":"Fountain Valley","state":"California","country":"United States","latitude":33.70918,"longitude":-117.95367},{"facility":"St Joseph Heritage Healthcare","status":null,"city":"Fullerton","state":"California","country":"United States","latitude":33.87029,"longitude":-117.92534},{"facility":"Clinical Research Institute","status":null,"city":"Los Angeles","state":"California","country":"United States","latitude":34.05223,"longitude":-118.24368},{"facility":"Artemis Institute for Clinical Research","status":null,"city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Alpine Clinical Research Center","status":null,"city":"Boulder","state":"Colorado","country":"United States","latitude":40.01499,"longitude":-105.27055},{"facility":"K2 Medical Research - Daytona Beach","status":null,"city":"Daytona Beach","state":"Florida","country":"United States","latitude":29.21081,"longitude":-81.02283},{"facility":"Flourish Research - Miami, LLC","status":null,"city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366},{"facility":"IMA Clinical Research St. Petersburg","status":null,"city":"St. Petersburg","state":"Florida","country":"United States","latitude":27.77086,"longitude":-82.67927},{"facility":"Care Access - Tampa","status":null,"city":"Tampa","state":"Florida","country":"United States","latitude":27.94752,"longitude":-82.45843},{"facility":"Charter Research - Lady Lake","status":null,"city":"The Villages","state":"Florida","country":"United States","latitude":28.93408,"longitude":-81.95994},{"facility":"Conquest Research","status":null,"city":"Winter Park","state":"Florida","country":"United States","latitude":28.6,"longitude":-81.33924},{"facility":"Cotton O'Neil Clinical Research Center","status":null,"city":"Topeka","state":"Kansas","country":"United States","latitude":39.04833,"longitude":-95.67804},{"facility":"Care Access - Lake Charles (Bayou Pines)","status":null,"city":"Lake Charles","state":"Louisiana","country":"United States","latitude":30.21309,"longitude":-93.2044},{"facility":"MedVadis Research Corporation","status":null,"city":"Waltham","state":"Massachusetts","country":"United States","latitude":42.37649,"longitude":-71.23561},{"facility":"Great Lakes Research Group, Inc.","status":null,"city":"Bay City","state":"Michigan","country":"United States","latitude":43.59447,"longitude":-83.88886},{"facility":"Clinvest Headlands Llc","status":null,"city":"Springfield","state":"Missouri","country":"United States","latitude":37.21533,"longitude":-93.29824},{"facility":"Center for Clinical Research","status":null,"city":"Winston-Salem","state":"North Carolina","country":"United States","latitude":36.09986,"longitude":-80.24422},{"facility":"Altoona Center For Clinical Research","status":null,"city":"Duncansville","state":"Pennsylvania","country":"United States","latitude":40.42341,"longitude":-78.4339},{"facility":"New Phase Research and Development","status":null,"city":"Knoxville","state":"Tennessee","country":"United States","latitude":35.96064,"longitude":-83.92074},{"facility":"FutureSearch Trials of Neurology","status":null,"city":"Austin","state":"Texas","country":"United States","latitude":30.26715,"longitude":-97.74306},{"facility":"Mercy Family Clinic","status":null,"city":"Dallas","state":"Texas","country":"United States","latitude":32.78306,"longitude":-96.80667},{"facility":"Houston Research Institute","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Have a history of axial-predominant low back pain\n* Have pain that is restricted to the low back or with a referral pattern limited to the proximal legs\n* Have a body mass index (BMI) ≥27 kilograms per square meter (kg/m2) at screening\n* Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight\n\nExclusion Criteria:\n\n* Have a non-axial origin low back pain\n* Have had botulinum or steroid injections to the spine within 1 year of screening\n* Have had trigger point injection to the spine within 6 months of screening\n* Have a self-reported change in body weight \\>5 kilograms (kg) (11 pounds) within 90 days prior to screening\n* Have been taking drugs to promote body weight reduction, including over-the-counter medications, within 90 days prior to screening\n* Have a prior or planned surgical treatment for obesity\n* Have Type 1 Diabetes, Type 2 Diabetes, or any other type of diabetes","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Retatrutide","description":"Administered SC"},{"type":"DRUG","name":"Placebo","description":"Administered SC"}],"primaryOutcomes":[{"measure":"Change from Baseline in Pain Intensity Per Numeric Rating Scale","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline, up to 72 weeks"}],"secondaryOutcomes":[{"measure":"Number of Participants with Reduction in Pain Intensity Per Numeric Rating Scale","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Number of Participants with Reduction in Body Weight","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Physical Function as Measured by Patient-Reported Outcomes Measurement Information Systems (PROMIS)","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Pain Interference as Measured by PROMIS","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Sleep as Measured by PROMIS","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Patient Reported Health Outcomes as Measured by Medical Outcomes Study 36-item Short Form Health Survey version 2 (SF-36v2)","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Waist Circumference","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Biomarkers of Inflammation as Measured by Blood Test","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Blood Pressure","description":null,"timeFrame":"Baseline, up to 72 weeks"},{"measure":"Change in Glycemic Control","description":null,"timeFrame":"Baseline, up to 72 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07035093"},{"nctId":"NCT07218354","title":"Cessation or Reduction of Alcohol Consumption in Veterans: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of a GLP-1 Receptor Agonist Semaglutide in U.S. Veterans With Alcohol Use Disorder","officialTitle":"CSP #2041 - Cessation or Reduction of Alcohol Consumption in VEterans: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of a GLP-1 Receptor Agonist Semaglutide in U.S. Veterans With Alcohol Use Disorder (CRAVE)","summary":"This clinical trial aims to test the effectiveness and safety of semaglutide, a GLP-1 receptor agonist, in treating moderate to severe alcohol use disorder (AUD) in Veterans. Participants who qualify will be randomly assigned to receive either semaglutide injections or placebo injections over a 28-week period, followed by a 4-week post-treatment safety assessment period. Participants receiving semaglutide will start with a low dose, gradually increasing to a maximum of 2.4 mg per week, depending on their tolerance. The primary measure of success will be a reduction in risky drinking, assessed through a reliable calendar-based interview method called the Timeline Follow-Back (TLFB), a well-validated calendar-based interview technique for recording daily alcohol consumption. The purpose of this research is to gather information on the effectiveness of semaglutide for treating AUD, potentially offering a new and more appealing treatment option.","detailedDescription":"AUD is one of the leading causes of disability worldwide. The prevalence of AUD is high, affecting 10.9% of US adults and 5.1% of adults worldwide. Oral naltrexone, the most widely prescribed medication for AUD, has a number needed to treat (NNT) to prevent a return to heavy drinking of 12, and thus is only modestly effective. Indeed, less than 2% of adults with AUD receive medication in a given year. Though the Department of Veterans Affairs promotes pharmacotherapy as a best practice, there are over 400,000 Veterans within the Veterans Health Administration (VHA) who have a diagnosis of AUD, with only about 40,000 being actively treated with pharmacotherapy (source: VA Quality Dashboard accessed 1/31/2025). As there have been no new Food and Drug Administration (FDA) approved medications in nearly two decades, there is an urgent need for novel treatments for AUD with superior efficacy and higher patient appeal. Based upon very promising clinical experience, retrospective studies, preclinical data, and recent pilot clinical trial results, the proposed clinical trial is designed to provide definitive evidence regarding the efficacy of the GLP-1 RA, semaglutide, compared to placebo for the treatment of AUD. This research will offer urgently needed information on the efficacy of GLP-1 RAs in the treatment of AUD in a diverse sample and is directly in line with the strategic priorities (SP) for VA Research codified by the Office of Research and Development (ORD) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).\n\nThe proposed study is a randomized, double-blind, placebo-controlled, intent-to-treat, two-arm, parallel, superiority multicenter clinical trial. Veterans with moderate to severe AUD, as diagnosed by DSM-5 criteria, and seeking treatment will be invited to participate. Enrolled participants, meeting eligibility criteria, will be randomized in a 1:1 ratio to receive either semaglutide 2.4 mg or placebo injections using a stratified random block randomization method. The stratification factors are participating site and body mass index (BMI). The study will be conducted in four phases. Phase 1 will be Recruitment, Consent and Screening, Phase 2 will be Randomization and Dose Initiation (the first 4 weeks of treatment), Phase 3 will be the Endpoint Ascertainment Period (24 weeks), and Phase 4 is the Post-Treatment Safety Assessment (4 weeks). Study visits will occur every 4 weeks.\n\nThe primary outcome, a reduction in risky drinking, will be assessed by raters at a centralized assessment center (CAC), blinded to treatment assignment, using the Timeline Follow-Back (TLFB). The TLFB is a validated retrospective calendar-based interview technique to record daily alcohol consumption. The TLFB has been widely used in AUD research for its reliability in capturing detailed drinking patterns.\n\nIntervention and Masking Semaglutide 2.4 mg: Participants assigned to the treatment group will undergo 28-week semaglutide treatment. The initial dosing period of 4 weeks (Phase 2) will be used for initiation of 0.25 mg for weeks 1 to 4. Further titration up to 2.4 mg weekly will occur starting at week 5 (Phase 3). Participants should be increased to their maximal tolerable dose. Increases will be considered only after the participant has been on the current dose for 4 weeks. Doses are not to exceed 2.4 mg weekly. Patients may have their dose reduced, maintain their current dose, or have slower titration to ensure tolerability and increase retention in the study. Doses are delivered via a pen, a cartridge-based device that calibrates medication delivery based on the desired dose. An extremely small needle (4-mm, 32-gauge needle - the size of 2 human hairs) is used to deposit the medication subcutaneously.\n\nPlacebo: Participants assigned to the placebo group will receive a placebo pen, which mimics the treatment pens under the masking rule by following the same treatment procedure.\n\nSample Size and Study Duration This study plans to randomize 438 Veterans, with 219 participants assigned to each group. Recruitment is expected to be completed over 32 months.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Alcohol Use Disorder"],"keywords":["Alcohol use Disorder","Semaglutide","Alcohol","GLP-1"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"VA Office of Research and Development","slug":"va-office-of-research-and-development","class":"FED"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":622,"dates":{"start":"2026-07-28","primaryCompletion":"2028-04-28","completion":"2029-05-26","firstPosted":"2025-10-20","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":19,"countries":["United States"],"locations":[{"facility":"VA Long Beach Healthcare System, Long Beach, CA","status":null,"city":"Long Beach","state":"California","country":"United States","latitude":33.76696,"longitude":-118.18923},{"facility":"VA Palo Alto Health Care System, Palo Alto, CA","status":null,"city":"Palo Alto","state":"California","country":"United States","latitude":37.44188,"longitude":-122.14302},{"facility":"VA Greater Los Angeles Healthcare System, West Los Angeles, CA","status":null,"city":"West Los Angeles","state":"California","country":"United States","latitude":34.0462,"longitude":-118.43068},{"facility":"Orlando VA Healthcare System, Orlando, FL","status":null,"city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Atlanta VA Medical and Rehab Center, Decatur, GA","status":null,"city":"Decatur","state":"Georgia","country":"United States","latitude":33.77483,"longitude":-84.29631},{"facility":"Edward Hines Jr. VA Hospital, Hines, IL","status":null,"city":"Hines","state":"Illinois","country":"United States","latitude":41.85364,"longitude":-87.8395},{"facility":"VA Ann Arbor Healthcare System, Ann Arbor, MI","status":null,"city":"Ann Arbor","state":"Michigan","country":"United States","latitude":42.27756,"longitude":-83.74088},{"facility":"Minneapolis VA Health Care System, Minneapolis, MN","status":null,"city":"Minneapolis","state":"Minnesota","country":"United States","latitude":44.97997,"longitude":-93.26384},{"facility":"Asheville VA Medical Center, Asheville, NC","status":null,"city":"Asheville","state":"North Carolina","country":"United States","latitude":35.60095,"longitude":-82.55402},{"facility":"Durham VA Medical Center, Durham, NC","status":null,"city":"Durham","state":"North Carolina","country":"United States","latitude":35.99403,"longitude":-78.89862},{"facility":"Louis Stokes VA Medical Center, Cleveland, OH","status":null,"city":"Cleveland","state":"Ohio","country":"United States","latitude":41.4995,"longitude":-81.69541},{"facility":"VA Portland Health Care System, Portland, OR","status":null,"city":"Portland","state":"Oregon","country":"United States","latitude":45.52345,"longitude":-122.67621},{"facility":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA","status":null,"city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"Philadelphia MultiService Center, Philadelphia, PA","status":null,"city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX","status":null,"city":"Dallas","state":"Texas","country":"United States","latitude":32.78306,"longitude":-96.80667},{"facility":"Michael E. DeBakey VA Medical Center, Houston, TX","status":null,"city":"Houston","state":"Texas","country":"United States","latitude":29.76328,"longitude":-95.36327},{"facility":"VA Salt Lake City Health Care System, Salt Lake City, UT","status":null,"city":"Salt Lake City","state":"Utah","country":"United States","latitude":40.76078,"longitude":-111.89105},{"facility":"VA Puget Sound Health Care System Seattle Division, Seattle, WA","status":null,"city":"Seattle","state":"Washington","country":"United States","latitude":47.60621,"longitude":-122.33207},{"facility":"William S. Middleton Memorial Veterans Hospital, Madison, WI","status":null,"city":"Madison","state":"Wisconsin","country":"United States","latitude":43.07305,"longitude":-89.40123}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Veteran.\n* WHO risk drinking level of Very High or High in the 28 days prior to screening.\n* Current diagnosis of moderate or severe AUD (i.e., meeting at least 4 of 11 DSM-5 AUD criteria) based on semi-structured diagnostic exam.\n* Able and willing to provide informed consent.\n* Has a desire to reduce their alcohol consumption.\n\nExclusion Criteria:\n\nMedical and Psychiatric:\n\n* Type 1 diabetes.\n* Current serious psychiatric illness (any psychotic disorder, bipolar 1 disorder, psychotic major depression, antisocial personality disorder, bulimia, or anorexia).\n* Current DSM-5 diagnosis of a SUD (other than moderate-to-severe alcohol, any nicotine, or mild cannabis use disorders).\n* At the time of randomization, moderate-to-severe alcohol withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) \\>8).\n* BMI \\<21 kg/m2.\n* Unstable body weight defined as \\>5% change in body weight (documented or self-report; intentional or not) in the 90 days prior to randomization.\n* History of acute or chronic pancreatitis.\n* History of diabetic ketoacidosis.\n* History of proliferative diabetic retinopathy.\n* History of ascites, advanced liver fibrosis, compensated cirrhosis with portal hypertension, decompensated cirrhosis, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatocellular carcinoma (HCC).\n* History of stage 3 fibrosis or stage 4 cirrhosis from a liver biopsy.\n* Presence of gastroparesis.\n* History of acute gallbladder disease in the prior 6 months.\n* History of advanced fibrosis or cirrhosis, including (but not limited to) transient elastography (liver stiffness) of \\>12 kPa, FIB-4 \\>= 2.67, ELF \\>= 9.8, MRE \\>= 3.63 kPa.\n* History of esophageal varices on endoscopy or imaging.\n* History of nodular liver, cirrhosis, splenomegaly, varices or splenic venous shunting or collaterals on prior imaging.\n* History or acute alcohol hepatitis (by liver biopsy or elevated bilirubin \\> 1.5 times the upper limit of normal).\n* History of primary biliary cholangitis.\n* History of primary sclerosing cholangitis.\n* History of autoimmune liver disease.\n* History of hemochromatosis.\n* History of Wilson's disease.\n* History of alpha1 antitrypsin deficiency related liver disease.\n* Current drug-induced liver disease.\n* Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).\n* Acute high risk of suicide requiring hospitalization at the time of screening or randomization.\n* Medical, psychiatric, behavioral, or logistical conditions which, in the judgement of the Local Site Investigator (LSI) or Co-Investigator (Co-I), make it unlikely the participant can participate in or complete the 24-week active phase of the study\n* Recent major cardiovascular event in the 90 days prior to randomization (myocardial infarction, stroke, New York Heart Association class IV heart failure, transient ischemic attack (TIA), or unstable angina.\n\nLaboratory\n\n* Hemoglobin A1c (HbA1c)\\>10.\n* Estimated glomerular filtration rate (eGFR) \\<30 mL/min.\n* Albumin \\< 3.5 g/dl.\n* Aspartate aminotransferase (AST) \\>3 the Upper Limit of Normal (ULN).\n* Alanine aminotransferase (ALT) \\>3 the ULN.\n* Lipase \\> 2 times the upper limit of normal.\n* Alkaline phosphatase \\> 1.5 times the ULN.\n* Total bilirubin \\> 1.5 times the ULN except with documented Gilbert's syndrome.\n* International Normalized Ratio (INR) \\> 1.3 unless due to anticoagulation therapy.\n* Platelet count \\<150,000/µL unless consistent with baseline and reflects the participant's habitual thrombocyte level, and there was no presence of portal hypertension.\n* Hepatitis B surface antigen positive.\n* Hepatitis C virus RNA positive - participants treated and cured of hepatitis C must have at least 2 years of negative testing.\n* Anti-HIV antibody positive test with uncontrolled or unstable treatment.\n* Positive urine drug screen for substances other than cannabis and prescribed medications.\n* Positive urine pregnancy test at screening in those considered of childbearing potential.\n\nConcurrent Treatments:\n\n* Current (within the past 30 days) use of pharmacotherapy for AUD (including oral or intramuscular naltrexone, acamprosate, disulfiram, topiramate).\n* Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue.\n* Current (within the past 30 days) use of the following medications with glucose-lowering properties: GLP-1 analogues; sulfonylurea; insulin and insulin products; dipeptidyl peptidase-4 (DPP-4) inhibitors; sodium-glucose cotransporter-2 (SGLT-2) inhibitors, meglitinides, thiazolidinediones or other medications that may interact with semaglutide.\n* Recent changes in dose (within 2 months of randomization) of psychiatric medications (i.e., antidepressants, antianxiety, mood stabilizing).\n\nOther\n\n* Pregnant, actively breastfeeding, or female of childbearing potential who is unwilling to use a highly effective method of contraception as defined by the NIH.\n* Currently enrolled in another therapeutic or investigational clinical trial.\n* Participant is incarcerated.","minimumAge":"18 Years","maximumAge":"80 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Semaglutide","description":"Weekly subcutaneous injections of semaglutide up to 2.4 mg/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5."},{"type":"DRUG","name":"Placebo","description":"Weekly subcutaneous injections of placebo."}],"primaryOutcomes":[{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 28 days of intervention","description":"Number of participants with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. The WHO risk drinking levels categorize alcohol consumption into four groups: low (level 1; 0-2.86 standard drinks/day for men; 0-1.43 drinks/day for women), moderate (level 2; 2.87-4.29 standard drinks/day for men; 1.44-2.86 drinks/day for women), high (level 3; 4.3-7.14 standard drinks/day for men; 2.87-4.29 drinks/day for women), and very high (level 4; \\>7.15 drinks/day for men; \\>4.3 drinks/day for women). One standard drink is 14g of alcohol. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.","timeFrame":"Change from Baseline to Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."}],"secondaryOutcomes":[{"measure":"Adverse events of special interest (Assessing safety and tolerability)","description":"Safety and tolerability will be assessed using number of participants with adverse events of special interest (AESIs) by comparing the proportion of participants experiencing an AESI in the semaglutide 2.4 mg treatment group versus placebo group.","timeFrame":"From randomization through week 32."},{"measure":"No heavy drinking days over the last 28 days of intervention.","description":"Number of participants with no heavy drinking days. Heavy drinking is defined as \\>4 standard drinks in a day for men and \\>3 for women. One standard drink is equal to 14 g of alcohol or approximately 12 oz beer, 5 oz wine, or 1.5 oz of liquor. The data will be derived from the Timeline Follow Back, which is a validated retrospective calendar-based interview technique to record daily alcohol consumption over a specified recall period (since the last assessment).","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level by Race category during the last 56 days of the trial.","description":"Number of participants by race category (White, Black, Other) with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. Each month of the ascertainment phase (weeks 5-28), the WHO risk drinking level will be calculated.","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level by age category (<65, ≥ 65) during last 28 days of intervention","description":"Number of participants by age category (\\<65, ≥ 65) at baseline with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. Each month of the ascertainment phase (weeks 5-28), the WHO risk drinking level will be calculated.","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level by psychiatric comorbidity during last 28 days of intervention","description":"Number of participants with a psychiatric comorbidity at baseline with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. Each month of the ascertainment phase (weeks 5-28), the WHO risk drinking level will be calculated.","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level by presence of other psychiatric treatments (medication and/or psychotherapy) during last 28 days of intervention","description":"Number of participants with psychiatric treatments (medication and/or psychotherapy) at baseline with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. Each month of the ascertainment phase (weeks 5-28), the WHO risk drinking level will be calculated.","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"Two-level reduction in the World Health Organization (WHO) risk drinking level by impulsivity category (low, moderate, high) during last 28 days of intervention","description":"Number of participants by impulsivity category (low, moderate, high) at baseline with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. Each month of the ascertainment phase (weeks 5-28), the WHO risk drinking level will be calculated. Impulsivity will be measured by the Barratt Impulsiveness Scale, which is a 30-item self-report instrument designed to access the personality/behavioral construct of impulsiveness. Items are scored on a 4-point scale: Rarely/Never = 1 Occasionally = 2 Often = 3 Almost Always/Always = 4. Total scores range from 30-120, with a higher score indicating a higher level of impulsivity. A score \\>/= 72 will be classified as high, 52-71 moderate, and \\< 52 low.","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"No heavy drinking days by Race category during last 28 days of intervention","description":"Number of participants by race category (White, Black, Other) with no heavy drinking days. Heavy drinking is defined as \\>4 standard drinks in a day for men and \\>3 for women. One standard drink is equal to 14 g of alcohol or approximately 12 oz beer, 5 oz wine, or 1.5 oz of liquor. The data will be derived from the Timeline Follow Back, which is a validated retrospective calendar-based interview technique to record daily alcohol consumption over a specified recall period (since the last assessment).","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"No heavy drinking days by age category (<65, ≥ 65) during last 28 days of intervention","description":"Number of participants by age category (\\<65, ≥ 65) at baseline with no heavy drinking days. Heavy drinking is defined as \\>4 standard drinks in a day for men and \\>3 for women. One standard drink is equal to 14 g of alcohol or approximately 12 oz beer, 5 oz wine, or 1.5 oz of liquor. The data will be derived from the Timeline Follow Back, which is a validated retrospective calendar-based interview technique to record daily alcohol consumption over a specified recall period (since the last assessment).","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."},{"measure":"No heavy drinking days by psychiatric comorbidity during last 28 days of intervention","description":"Number of participants with a psychiatric comorbidity at baseline with no heavy drinking days. Heavy drinking is defined as \\>4 standard drinks in a day for men and \\>3 for women. One standard drink is equal to 14 g of alcohol or approximately 12 oz beer, 5 oz wine, or 1.5 oz of liquor. The data will be derived from the Timeline Follow Back, which is a validated retrospective calendar-based interview technique to record daily alcohol consumption over a specified recall period (since the last assessment).","timeFrame":"Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28."}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07218354"},{"nctId":"NCT07463846","title":"A Study to Evaluate ALN-2232 in Participants With Obesity","officialTitle":"A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALN-2232 as Monotherapy and Co-initiated With Tirzepatide in Adult Participants With Obesity","summary":"The purpose of this study is to:\n\n* evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of ALN-2232 in patients with obesity\n* evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 in patients with obesity\n* evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 co-initiated with tirzepatide in patients with obesity","detailedDescription":null,"peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Obesity"],"keywords":["siRNA, RNAi therepeutic"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Alnylam Pharmaceuticals","slug":"alnylam-pharmaceuticals","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE1","PHASE2"],"slugs":["phase-1","phase-2"],"labels":["Phase 1","Phase 2"],"label":"Phase 1 / Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":156,"dates":{"start":"2026-03-02","primaryCompletion":"2027-04-27","completion":"2028-03-02","firstPosted":"2026-03-11","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["Canada"],"locations":[{"facility":"Clinical Trial Site","status":"RECRUITING","city":"Mount Royal","state":null,"country":"Canada","latitude":45.51675,"longitude":-73.64918}],"eligibility":{"criteria":"Inclusion Criteria:\n\nAll Parts:\n\n* Has a body mass index (BMI) of ≥30 kg/m\\^2 and \\<40 kg/m\\^2\n* Has a hemoglobin A1c (HbA1c) \\<6.5%\n\nExclusion Criteria:\n\nAll Parts:\n\n* Has any clinically significant concomitant disease, medical condition, or abnormal laboratory finding that could compromise participant safety or confound interpretation of study results\n* Receiving therapies for chronic weight management or antidiabetic medications\n\nNote: other protocol defined inclusion/exclusion criteria apply","minimumAge":"18 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"ALN-2232","description":"ALN-2232 will be administered subcutaneously (SC)"},{"type":"DRUG","name":"Placebo","description":"Placebo will be administered SC"},{"type":"DRUG","name":"Tirzepatide","description":"Tirzepatide will be administered SC"}],"primaryOutcomes":[{"measure":"Part A: Frequency of Adverse Events (AEs)","description":null,"timeFrame":"Up to 12 months"},{"measure":"Part B: Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline up to Month 6"},{"measure":"Part C: Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline up to Month 6"}],"secondaryOutcomes":[{"measure":"Part A: Change from Baseline in Proteins in Adipose Tissue","description":null,"timeFrame":"Baseline up to Month 12"},{"measure":"Part A: Area Under the Plasma Concentration-time Curve (AUC) of ALN-2232 in Plasma","description":null,"timeFrame":"Predose and up to 15 days postdose"},{"measure":"Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-2232 in Plasma","description":null,"timeFrame":"Predose and up to 15 days postdose"},{"measure":"Part A: Time to Maximum Plasma Concentration (Tmax) of ALN-2232 in Plasma","description":null,"timeFrame":"Predose and up to 15 days postdose"},{"measure":"Part A: Fraction of ALN-2232 excreted in urine","description":null,"timeFrame":"Predose and up to 8 days postdose (fe)"},{"measure":"Part A: Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline up to Month 12"},{"measure":"Part B and Part C: Concentrations of ALN-2232 in Plasma","description":null,"timeFrame":"Predose and up to 6 months postdose"},{"measure":"Part B and Part C: Percent Change from Baseline in Body Weight","description":null,"timeFrame":"Baseline up to Month 12"},{"measure":"Part B and Part C: Change from Baseline in Body Fat Mass and Lean Mass","description":"Measured by dual x-ray absorptiometry (DXA)","timeFrame":"Baseline up to Month 12"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07463846"},{"nctId":"NCT07496463","title":"Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)","officialTitle":"Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)","summary":"The investigators plan to test the efficacy and safey of 6-months of open-label setmelanotide to treat obesity in a single patient with pseudohypoparathyroidism type 1a due to a GNAS mutation.","detailedDescription":"Pseudohypoparathyroidism type 1A (PHP1a) is a rare genetic disorder caused by impaired G-protein signaling due to heterozygous mutations in the gene GNAS. Multiple abnormalities may result including hypocalcemia, hypothyroidism, hypogonadism, and developmental delay. Obesity also commonly occurs due to impaired signaling through the melanocortin-4 receptor (MC4R). The melanocortin-4 receptor agonist setmelanotide has been proposed as a potential yet untested treatment strategy for patients with pathogenic GNAS variants.\n\nIn the current study, the investigators plan to test effects of setmelanotide on body weight, body composition, and metabolic parameters in a single patient with PHP1a. GNAS is a paternally imprinted gene, and thus PHP1a results primarily when a mutation is inherited on the preferentially expressed maternal allele. However, detailed studies have shown that 1) GNAS is not imprinted in all areas of the brain, and 2) in regions where imprinting does occur, it is incomplete (e.g., low levels of paternally inherited protein remain expressed). As such, the investigators hypothesize that setmelanotide will augment MC4R signaling by maximally stimulating low levels of intact, paternally inherited GNAS in patients with PHP1a and milder GNAS disorders.\n\nThis project stands to identify a novel patient population with rare monogenic obesity who may benefit from setmelanotide therapy and who is classically resistant to mainstream obesity medications. Evidence of clinical benefit in this single patient would serve as proof of concept for a larger scale clinical study of patients with PHP1a and GNAS mutations.","peptideSlugs":["setmelanotide"],"peptideNames":["Setmelanotide"],"conditions":["Pseudohypoparathyroidism Type 1a","Obesity"],"keywords":["pseudohypoparathyroidism type 1a","obesity","setmelanotide"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Massachusetts General Hospital","slug":"massachusetts-general-hospital","class":"OTHER"},"collaborators":[],"status":{"raw":"ENROLLING_BY_INVITATION","group":"active","label":"Enrolling by invitation"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":1,"dates":{"start":"2026-07-21","primaryCompletion":"2027-04-30","completion":"2027-04-30","firstPosted":"2026-03-27","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Massachusetts General Hospital","status":null,"city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Known patient with PHP1a (confirmed GNAS mutation)\n* Optimized therapy for diabetes and dyslipidemia\n\nExclusion Criteria:\n\n\\- Use of medications that may affect endpoints that are changed within 3 months prior to Baseline or that are likely to require a change in dose during the open-label treatment period","minimumAge":null,"maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Setmelanotide","description":"Setmelanotide will be prescribed at the standard initial dose of 2 mg SC daily. The treatment will be uptitrated at the 2-Week visit to 3 mg SC daily if tolerated. We will continue this maximal dose for a period of 6 months."}],"primaryOutcomes":[{"measure":"Greater than or Equal to 5% Weight loss","description":"Greater than or equal to 5% weight loss from baseline","timeFrame":"Baseline to 6 Months"}],"secondaryOutcomes":[{"measure":"Percent Weight Loss","description":"Percent change in weight from baseline","timeFrame":"Baseline to 3 Months, Baseline to 6 Months"},{"measure":"Trunk Fat Mass","description":"Trunk fat mass measured on dual-energy x-ray absorptiometry scan","timeFrame":"Baseline to 6 Months"},{"measure":"Hemoglobin A1c","description":"Hemoglobin A1c (%) measured on blood draw","timeFrame":"Baseline to 3 Months, Baseline to 6 Months"},{"measure":"Serum Triglycerides","description":"Serum triglycerides (mg/dL) measured on blood draw","timeFrame":"Baseline to 3 Months, Baseline to 6 Months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07496463"},{"nctId":"NCT07568509","title":"Identifying Oxytocin Deficiency in Pediatric Patients With Pituitary Disease","officialTitle":"Identifying a Provocation Test for Diagnosis of Oxytocin Deficiency in Youth With Hypopituitarism","summary":"An open-labeled, interventional pilot trial, 10 youth with AVP-D and 10 PD matched for age, sex, and BMI will be recruited from Pediatric Endocrinology and Neuroendocrinology at Massachusetts General Hospital and in the community. This study tests the hypothesis that oral estrogen/progestin will stimulate endogenous oxytocin release in control subjects. Eligible participants will receive two tablets in a single administration containing a total of 1 mg of norethindrone acetate 70 mcg of ethinyl estradiol. Sampling for blood and saliva will take place at baseline and approximately 24 hours following study drug administration. Neuropsychological assessment (anxiety, mood and emotion regulation; impulse control; aberrant eating behaviors; social cognition and functioning; quality of life) will be assessed at baseline to characterize the study population.","detailedDescription":null,"peptideSlugs":["vasopressin","oxytocin"],"peptideNames":["Vasopressin","Oxytocin"],"conditions":["Arginine Vasopressin Deficiency","Oxytocin Deficiency","Pediatric Disease","Hypopituitarism"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Massachusetts General Hospital","slug":"massachusetts-general-hospital","class":"OTHER"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["EARLY_PHASE1"],"slugs":["early-phase-1"],"labels":["Early Phase 1"],"label":"Early Phase 1","highest":0.5},"studyType":"INTERVENTIONAL","enrollment":20,"dates":{"start":"2026-08","primaryCompletion":"2027-04","completion":"2027-04","firstPosted":"2026-05-05","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Massachusetts General Hospital","status":"RECRUITING","city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977}],"eligibility":{"criteria":"Inclusion criteria (participants with AVP-D):\n\n* AVP-D diagnosed in clinic using standard of care diagnostic tools;\n* Stable pituitary hormone replacement (no change in dose of hormone replacement in six weeks prior to baseline);\n* If on estrogen/progestin, female participants agree to stop for at least 6 weeks prior to Main study visits;\n* English language proficiency.\n\nInclusion criteria (participants with hypopituitary disease):\n\n* Hypopituitary disease diagnosis;\n* If receiving pituitary hormone replacement, no change in dose in six weeks prior to baseline);\n* If on estrogen/progestin, participants agree to stop for at least 6 weeks prior to Main study visits;\n* English language proficiency.\n\nExclusion criteria (all participants):\n\n* History of pulmonary embolism or unprovoked deep venous thrombosis;\n* History of breast/endometrial cancer as well as current therapies on estrogen modulators/blockers (i.e., tamoxifen, raloxifene, aromatase inhibitors);\n* History of stroke, transient ischemic attack, myocardial infarction, angina pectoris, or peripheral arterial disease;\n* Pregnancy or breastfeeding within the last 8 weeks;\n* Medication changes within 2 weeks of enrollment or within 5 half-lives of the respective medication;\n* History of stage 3 chronic kidney disease or cirrhosis;\n* Any significant illness or condition that the investigator determines could interfere with study participation, data collection or safety;\n* Active tobacco smoking or nicotine patch use;\n* Psychosis or active suicidality.","minimumAge":"7 Years","maximumAge":"21 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Norethindrone Acetate-Ethinyl Estradiol","description":"Norethindrone Acetate-Ethinyl Estradiol will be given to participants in both cohorts, arginine-vasopressin deficiency cohort and control cohort."}],"primaryOutcomes":[{"measure":"Change in neurophysin-1 from baseline","description":"Change in neurophysin-1 levels from baseline to 24 hours","timeFrame":"0 minutes (Baseline) and 24 hours"}],"secondaryOutcomes":[{"measure":"Change in oxytocin from baseline","description":"Change in oxytocin from baseline to 24 hours","timeFrame":"0 minutes (Baseline) and 24 hours"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07568509"},{"nctId":"NCT07575399","title":"Efficacy, Safety and Tolerability of Switching From Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) to Maridebart Cafraglutide in Adults With Obesity or Overweight (MARITIME-SWITCH)","officialTitle":"A Phase 3, Open-label Trial to Evaluate the Efficacy, Safety and Tolerability of Switching From the Glucagon-like Peptide-1 Receptor Agonists to Maridebart Cafraglutide in Adult Participants With Obesity or Overweight","summary":"Efficacy, safety and tolerability of switching from GLP-1RA to maridebart cafraglutide in adults with obesity or overweight.","detailedDescription":null,"peptideSlugs":["maridebart-cafraglutide","glucagon"],"peptideNames":["Maridebart cafraglutide","Glucagon"],"conditions":["Obesity or Overweight"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Amgen","slug":"amgen","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":300,"dates":{"start":"2026-05-11","primaryCompletion":"2028-01-03","completion":"2028-02-28","firstPosted":"2026-05-08","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":44,"countries":["Puerto Rico","United States"],"locations":[{"facility":"Cahaba Research, Inc.","status":"RECRUITING","city":"Pelham","state":"Alabama","country":"United States","latitude":33.28567,"longitude":-86.80999},{"facility":"Arizona Clinical Trials","status":"RECRUITING","city":"Chandler","state":"Arizona","country":"United States","latitude":33.30616,"longitude":-111.84125},{"facility":"Epic Medical Research - Sun City","status":"RECRUITING","city":"Sun City","state":"Arizona","country":"United States","latitude":33.59754,"longitude":-112.27182},{"facility":"Desert Oasis Healthcare Medical Group","status":"RECRUITING","city":"Palm Springs","state":"California","country":"United States","latitude":33.8303,"longitude":-116.54529},{"facility":"Inland Empire Liver Foundation","status":"RECRUITING","city":"Rialto","state":"California","country":"United States","latitude":34.1064,"longitude":-117.37032},{"facility":"Peninsula Research Associates","status":"RECRUITING","city":"Rolling Hills Estates","state":"California","country":"United States","latitude":33.78779,"longitude":-118.35813},{"facility":"Apex Clinical Research","status":"RECRUITING","city":"San Diego","state":"California","country":"United States","latitude":32.71571,"longitude":-117.16472},{"facility":"Southern California Clinical Research","status":"RECRUITING","city":"Santa Ana","state":"California","country":"United States","latitude":33.74557,"longitude":-117.86783},{"facility":"University of Florida Department of Medicine","status":"RECRUITING","city":"Gainesville","state":"Florida","country":"United States","latitude":29.65163,"longitude":-82.32483},{"facility":"Aga Clinical Trials","status":"RECRUITING","city":"Hialeah","state":"Florida","country":"United States","latitude":25.8576,"longitude":-80.27811},{"facility":"South Florida Clinical Research","status":"RECRUITING","city":"Margate","state":"Florida","country":"United States","latitude":26.24453,"longitude":-80.20644},{"facility":"New Horizon Research Center","status":"RECRUITING","city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366},{"facility":"Research Institute of South Florida","status":"RECRUITING","city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366},{"facility":"Clinical Neuroscience Solutions","status":"RECRUITING","city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Florida Institute for Clinical Research","status":"RECRUITING","city":"Orlando","state":"Florida","country":"United States","latitude":28.53834,"longitude":-81.37924},{"facility":"Progressive Medical Research","status":"RECRUITING","city":"Port Orange","state":"Florida","country":"United States","latitude":29.13832,"longitude":-80.99561},{"facility":"Charter Research - The Villages","status":"RECRUITING","city":"The Villages","state":"Florida","country":"United States","latitude":28.93408,"longitude":-81.95994},{"facility":"Nsc Research","status":"RECRUITING","city":"Johns Creek","state":"Georgia","country":"United States","latitude":34.02893,"longitude":-84.19858},{"facility":"Rophe Adult and Pediatric Medicine/Sky Clinical Research Network Group","status":"RECRUITING","city":"Union City","state":"Georgia","country":"United States","latitude":33.58706,"longitude":-84.54243},{"facility":"North Georgia Clinical Research","status":"RECRUITING","city":"Woodstock","state":"Georgia","country":"United States","latitude":34.10149,"longitude":-84.51938},{"facility":"Solaris Clinical Research","status":"RECRUITING","city":"Meridian","state":"Idaho","country":"United States","latitude":43.61211,"longitude":-116.39151},{"facility":"Endeavor Health","status":"RECRUITING","city":"Skokie","state":"Illinois","country":"United States","latitude":42.03336,"longitude":-87.73339},{"facility":"Pennington Biomedical Research Center","status":"RECRUITING","city":"Baton Rouge","state":"Louisiana","country":"United States","latitude":30.44332,"longitude":-91.18747},{"facility":"Arcturus Healthcare, Public Limited Company, Troy Internal Medicine Research Division","status":"RECRUITING","city":"Troy","state":"Michigan","country":"United States","latitude":42.60559,"longitude":-83.14993}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Body Mass Index (BMI) ≥ 25 at screening.\n* Weight loss of ≥ 10% on weekly GLP-1 RA.\n* Stable body weight.\n* Stable dose of GLP-1RA.\n* Stable gastrointestinal (GI) tolerability.\n* Contraception for females.\n* Willingness to follow trial procedures for the duration of the trial.\n\nExclusion Criteria:\n\n* Obesity induced by other endocrine disorders (ex: Cushing's syndrome).\n* Previous or planned surgical, endoscopic or device-based treatment for obesity.\n* History of malignancy.\n* Type 1/Type 2 diabetes mellitus (DM).\n* Family or personal history of medullary thyroid cancer.\n* Previous participation in a Maridebart Cafraglutide trial.","minimumAge":"18 Years","maximumAge":"99 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Maridebart Cafraglutide","description":"Maridebart cafraglutide will be administered via subcutaneous (SC) injection."}],"primaryOutcomes":[{"measure":"Percent Change from Baseline in Body Weight at Week 68","description":null,"timeFrame":"Week 68"}],"secondaryOutcomes":[{"measure":"Percent Change in Body Weight Prior to the Start of Weekly GLP-1RA at Week 68","description":null,"timeFrame":"Week 68"},{"measure":"Percentage of Participants Maintaining ≥ 80% of the Body Weight Reduction Achieved with Prior Weekly GLP-1RA Treatment at Week 68","description":null,"timeFrame":"Week 68"},{"measure":"Percent Maintenance of the Body Weight Reduction Achieved with Prior Weekly GLP-1RA Treatment at Week 68","description":null,"timeFrame":"Week 68"},{"measure":"Plasma Concentration of Maridebart Cafraglutide at Week 68","description":null,"timeFrame":"Week 68"},{"measure":"Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events","description":null,"timeFrame":"Up to 84 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07575399"},{"nctId":"NCT07587775","title":"The Effect of Osteoporotic Medications on Vertebral Bone Quality Score","officialTitle":"The Effect of Osteoporotic Medications on Vertebral Bone Quality Score","summary":"The goal of this clinical trial is to determine the change in VBQ score, T score, TBS, and Hounsfield Units (HU) after 3-6 months of treatment with abaloparatide in osteoporotic patients who will undergo spinal fusion and decompression for lumbar degenerative disease. The main question\\[s\\] it aims to answer is:\n\nDoes abaloparatide improve bone density in these patients, as defined by VBQ score compared to traditional methods such as DEXA and Hounsfield Units Does abaloparatide reduce the incidence of postoperative mechanical complications, including adjacent segment disease, subsidence, and proximal junctional kyphosis (PKJ)?\n\nParticipants will undergo a presurgical assessments and trained in clinic on the subcutaneous application of abaloparatide. Prior to treatment, patients will have baseline assessments, including a lumbar MRI, DEXA scan, and lumbar CT. Post-surgically, participants will administer abaloparatide and return to clinic after 3-6 months for follow-up assessments including a new MRI, lumbar CT, and DEXA scan. Patients will be followed for up to 2 years postoperatively to identify complications such as adjacent segment disease, pseudarthrosis, failure of instrumentation, and PJK.","detailedDescription":null,"peptideSlugs":["abaloparatide"],"peptideNames":["Abaloparatide"],"conditions":["Lumbar Degenerative Disease"],"keywords":["Osteoporosis","Spinal Fusion","Lumbar Degenerative Disease","Abaloparatide"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"State University of New York at Buffalo","slug":"state-university-of-new-york-at-buffalo","class":"OTHER"},"collaborators":[],"status":{"raw":"ENROLLING_BY_INVITATION","group":"active","label":"Enrolling by invitation"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":60,"dates":{"start":"2026-06-18","primaryCompletion":"2028-06-01","completion":"2028-12-31","firstPosted":"2026-05-14","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"University at Buffalo Neurosurgery","status":null,"city":"Buffalo","state":"New York","country":"United States","latitude":42.88645,"longitude":-78.87837}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Diagnosis of Osteoporosis based on the following criteria:\n\n  * Fragility fracture (low trauma fracture similar to a fall from a standing position except for fracture to the skull, face, fingers, and toes)\n  * T score \\<-2.5\n  * T-score -1 to -2.5 with a high FRAX or high TBS adjusted FRAX (with a 10-year probability of major osteoporotic fracture ≥20% or a 10-year probability of hip fracture ≥3%)\n* Fulfill criteria for treatment with anabolic therapy, as outlined in the American Association of Clinical Endocrinologist guidelines for the diagnosis and treatment of postmenopausal osteoporosis in women and Evidence-Based Guideline for the management of osteoporosis in men.\n* Lumbar Degenerative Disease as evidenced by a diagnosis of spondylosis, spondylolisthesis, degenerative disc disease with spinal stenosis, and degenerative scoliosis\n* Have or be willing to have a DEXA scan, lumbar MRI, and lumbar CT within 3 months of the start of Abaloparatide\n* If on thyroid hormone replacement, having been on it for at least 6 months\n\nExclusion Criteria:\n\n* Previous lumbar surgery\n* Past medical history of: sarcoma, including osteosarcoma, paget disease or other skeletal malignancies, unexplained elevations of alkaline phosphatase, prior external beam radiation, and pre-existing hypercalcemia\n* Diagnosis of secondary osteoporosis\n* Vitamin D deficit\n* History of prior treatment with TPTD and ABL","minimumAge":"50 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Abaloparatide","description":"3-6 months of treatment with abaloparatide in osteoporotic patients who will undergo spinal fusion and decompression for lumbar degenerative disease"}],"primaryOutcomes":[{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Vertebral Bone Quality","timeFrame":"6 weeks post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Hounsfield Units","timeFrame":"6 weeks post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using DEXA (Dual-Energy X-ray ABsorptiometry)","timeFrame":"6 weeks post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Vertebral Bone Quality","timeFrame":"6 months post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Hounsfield Units","timeFrame":"6 months post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using DEXA (Dual-Energy X-ray ABsorptiometry)","timeFrame":"6 months post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Vertebral Bone Quality","timeFrame":"12 months post-op"},{"measure":"Improvement in Bone Quality","description":"Improvement in bone quality, using Hounsfield Units","timeFrame":"12 months post-op"}],"secondaryOutcomes":[{"measure":"Surgical Complications","description":"Presence of complications associated with fusion, such as Proximal Junctional Kyphosis (PJK), proximal junctional failure (PJF), pseudoarthrosis, subsidence, adjacent segment disease, mechanical failure, reoperation, and patient-reported outcomes.","timeFrame":"6 weeks post-operatively"},{"measure":"Surgical Complications","description":"Presence of complications associated with fusion, such as PJK, PJF, pseudoarthrosis, subsidence, adjacent segment disease, mechanical failure, reoperation, and patient-reported outcomes.","timeFrame":"6 months post-operatively"},{"measure":"Surgical Complications","description":"Presence of complications associated with fusion, such as PJK, PJF, pseudoarthrosis, subsidence, adjacent segment disease, mechanical failure, reoperation, and patient-reported outcomes.","timeFrame":"12 months post-operatively"},{"measure":"Surgical Complications","description":"Presence of complications associated with fusion, such as PJK, PJF, pseudoarthrosis, subsidence, adjacent segment disease, mechanical failure, reoperation, and patient-reported outcomes.","timeFrame":"24 months post-operatively"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07587775"},{"nctId":"NCT07721623","title":"The Efficacy of Carbitocin in Reduction of Blood Loss During Myomectomy","officialTitle":"A Randomized Controlled Trial of the Efficacy of Carbitocin in Reduction of Blood Loss During Myomectomy","summary":"The uterine fibroids are the most common benign tumors found in the female reproductive system. Uterine fibroids commonly cause heavy menstrual periods. The prevalence of uterine fibroids is significantly affecting up to 70-80% of women by the age of 50, with an inconsistent impact on women of African origin. Carbitocin is a synthetic analogue of oxytocin which has a longer half-life than oxytocin. A Cochrane review and meta-analysis studies found that carbitocin reduced the use of additional uterotonics and transfusion. However, few of these studies was done during myomectomy.","detailedDescription":"INTRODUCTION The uterine fibroids - heavy bleeding during myomectomy.\n\nThe prevalence - 70-80% of women by the age of 50.\n\nCommon in black women.\n\nCabetocin is a synthetic analogue of oxytocin, with a longer half-life than oxytocin.\n\nA Cochrane review and meta-analysis noted that cabetocin reduced the use of additional uterotonics and blood transfusion, with only few during myomectomy and results inconsistent\n\nAim To determine the efficacy of cabetocin in reduction of blood loss during myomectomy.\n\nSpecific Objectives To evaluate the impact of cabetocin on prevention of perioperative blood loss during myomectomy.\n\nTo assess the transfusion rates, hospital stay, duration of surgery, cadre and years of practice of the surgeon.\n\nTo determine if the FIGO stage (Munro, 2011) of the Myoma affect the cabetocin effect.\n\nTo assess any intraoperative side effect.\n\nJUSTIFICATION Uterine fibroid - 20%-40% are symptomatic and contribute to subfertility\n\nHysterectomy has been done for uncontrollable bleeding during myomectomy\n\nHence, interventions to lessen bleeding during myomectomy and reduce the number of hysterectomy is vital.\n\nCabetocin is widely recommendation in obstetrics but has limited use in gynaecology; hence the study\n\nSTATEMENT OF PROBLEM Myomectomy is associated with significant blood loss and this causes adverse outcomes for patients.\n\nMany haemostatic agents during myomectomy have been explored\n\nHowever, none has given the desired result.\n\nCabetocin though, promising in obstetrics practice is yet to be significantly proven in gynaecological practice like myomectomy\n\nMETHODOLOGY Multicentre double-blind randomized placebo-controlled trial design\n\nIt will be conducted in Ebonyi State across the three tertiary hospitals - (DUFUTH, AEFUTHA and NOFIC)\n\nComprise women undergoing open abdominal myomectomy who fits into the eligibility criteria.\n\nFollowing Sample size determination = 300 participants per centre = 900 total participants.\n\nEthical approvals and support letters from the three centers will be made available\n\nInformed consent will be secured from all participants prior to recruitment.\n\nParticipants will be recruited from clinics and surgical outreaches.\n\nRandomization and concealment will be done by the pharmacist.\n\nNormal pre, intra and post op care will be observed as in open myomectomy with 22g tourniquet.\n\nSpinal-Epidural Anesthesia will be used\n\nGroup A will receive 100μg intravenous cabetocin at induction of anesthesia\n\nGroup B will receive intravenous placebo (normal saline).\n\nBlood loss estimation will follow the method described by Elousov et al.\n\nPreoperative HB done 12hours before the surgery\n\nPostoperative HB done 48hours after the surgery\n\nEBL(liters) = (EBV (Weight in kg x 65ml / 1000) X difference in HB (Hi-Hf) ) / Average HB (Hi-+ Hf) 2 FIGO STAGING OF MYOMA Type 0: Pedunculated intracavitary\n\nType 1: \\<50% intramural extension\n\nType 2: ≥50% intramural extension\n\nType 3: 100% intramural, contacting endometrium\n\nType 4: 100% intramural, zero contact with either the endometrium or the outer serosal surface\n\nType 5: Subserosal, ≥50% intramural\n\nType 6: Subserosal, \\<50% intramural\n\nType 7: Pedunculated subserosal\n\nType 8: Non-myometrial or ectopic\n\nPROFOMA\n\nSERIAL NUMBER:…………………………………….……………………………………………………………. (A) GENERAL CHARACTERISTICS\n\n1. Age:………………………………………Parity:……….………….……………………………………………..\n2. Weight (kg): ........................................ Height (meters):.........................................\n3. Blood group:…………………………….Rhesus Factor:…………………………………………………. (B) HAEMOGLOBIN ESTIMATION Pre Myomectomy HB:…………………………………………………………………………………………… Post Myomectomy HB:………………………………………………………………………………………….. (C). BLOOD TRANSFUSION RATE:…………………………………………………………………………… (D). DURATION OF HOSPITAL STAY: ............................................................................\n\n(E). CADRE OF THE SURGEON:……………………………………………………………………………….. (F). DURATION OF SURGERY:………………………………………………………………………………….. (G). NOTICED INTRAOPERATIVE SIDE EFFECTS: ……………………………………………………… ………………………………………………………………………………………………………………………………\n\n……………………………………………………………………………………………………………………………… (H). FIGO STAGING OF THE MYOMA:…………………………………………………………………….. (I). DURATION OF SURGERY:………………………………………………………………………………….. (J). NUMBER OF YEARS OF PRACTICE OF THE SURGEON: ……………………………………… (K). PROFESSIONAL CADRE OF THE SURGEON:………………………………………………………\n\nData will be collected with a profoma and analyzed with SPSS v25.\n\nContinuous variables will be expressed as means ± 2SD, normal distributed data = Student's t-test, and non normal distributed data = Mann-Whitney U test.\n\nCategorical variables will be expressed in frequencies and percentages and compared with Chi-square tests.\n\nA p-value \\< 0.05 will be considered significant.","peptideSlugs":["carbetocin"],"peptideNames":["Carbetocin"],"conditions":["Blood Loss, Surgical"],"keywords":["Carbetocin","Uterotonics","blood loss","myomectomy."],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Alex Ekwueme Federal University Teaching Hospital","slug":"alex-ekwueme-federal-university-teaching-hospital","class":"OTHER"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["EARLY_PHASE1"],"slugs":["early-phase-1"],"labels":["Early Phase 1"],"label":"Early Phase 1","highest":0.5},"studyType":"INTERVENTIONAL","enrollment":900,"dates":{"start":"2026-08-15","primaryCompletion":"2028-08-14","completion":"2028-08-14","firstPosted":"2026-07-23","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":0,"countries":[],"locations":[],"eligibility":{"criteria":"Inclusion Criteria:\n\n* All consented women booked for myomectomy.\n* No know allergy to Cabetocin.\n* Billed for open abdominal myomectomy.\n\nExclusion Criteria:\n\n* Declined consent\n* Allergy to Cabetocin\n* Planned for additional uterotonic\n* Prior history of thromboembolism,\n* With bleeding disorders\n* History of renal disease\n* History of liver pathology\n* Chronic anaemia\n* Billed for vaginal or laparoscopic myomectomy\n* Patients received preoperative embolization or Gn-Rh analogue.\n* Type 8: Non-myometrial or ectopic","minimumAge":null,"maximumAge":null,"sex":"FEMALE","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Carbetocin","description":"Carbitocin is an oxytocid with longer half life"}],"primaryOutcomes":[{"measure":"Haemoglobin Change","description":"Pre and Post operative Haemoglobin will be compared","timeFrame":"24months"}],"secondaryOutcomes":[{"measure":"Transfusion rates","description":"The number of units of blood used","timeFrame":"24months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07721623"},{"nctId":"NCT07723833","title":"A Study to Investigate the Relative Bioavailability and Safety of Different Oral Formulations of Elecoglipron in Healthy Participants","officialTitle":"A Phase I, Randomized, Single-dose, Crossover, 2-Period, Open-Label Study to Assess the Relative Bioavailability and Safety of Different Oral Formulations of Elecoglipron in Healthy Participants","summary":"The purpose of this study is to measure the pharmacokinetics (PK-how the body processes the study drug) of elecoglipron in healthy participants when taken by mouth as different formulations.","detailedDescription":"This is a phase I, open-label, randomized, 2-period crossover study with 4-cohorts. All 4 cohorts are independent and non-sequential parts in this study. Each cohort will evaluate 2 formulations (test formulation and reference formulation) of elecoglipron across 2 study treatment periods. Participants within each cohort will be randomized to one of 2 treatment sequences (Test-Reference or Reference-Test).\n\nIn total 3 formulations will be evaluated at 2 dose levels each:\n\n* Reference formulation\n* Test formulation 1\n* Test formulation 2\n\nThe study will comprise:\n\n* A Screening Period.\n* 2 treatment periods in each cohort - Period 1, and Period 2 during which participants will be admitted to the Clinical Unit and receive a single oral dose of elecoglipron in each period.\n* A final Follow-up Visit.","peptideSlugs":["glucagon"],"peptideNames":["Glucagon"],"conditions":["Healthy Participants"],"keywords":["Glucagon-like peptide receptor agonist (GLP-1RA)","Type 2 Diabetes Mellitus (T2DM)","Glucose Metabolism Disorders","Metabolic Diseases","Obesity management","Pharmacokinetics","Relative bioavailability","Obesity and Related Co-morbidities"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"},{"slug":"type-2-diabetes","label":"Type 2 diabetes"}],"sponsor":{"name":"AstraZeneca","slug":"astrazeneca","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"NOT_YET_RECRUITING","group":"active","label":"Not yet recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":152,"dates":{"start":"2026-07-27","primaryCompletion":"2026-11-18","completion":"2026-11-18","firstPosted":"2026-07-23","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"Research Site","status":null,"city":"Glendale","state":"California","country":"United States","latitude":34.14251,"longitude":-118.25508},{"facility":"Research Site","status":null,"city":"Brooklyn","state":"Maryland","country":"United States","latitude":39.23039,"longitude":-76.60219}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Healthy participants with suitable veins for cannulation or repeated venipuncture.\n* All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.\n* Females of childbearing potential must not be lactating and if heterosexually active, must agree to use an approved method of highly effective contraception.\n* Females of non-childbearing potential must be confirmed at screening visit as postmenopausal or have documentation of irreversible surgical sterilization.\n* Sexually active fertile male participants with partners of childbearing potential must adhere to the study specific contraception methods.\n* Have a body mass index between 18.5 and 30 kg/m2 inclusive and weigh at least 50 kg.\n\nExclusion Criteria:\n\n* History of any clinically important disease or disorder.\n* History of acute pancreatitis.\n* History or presence of gastrointestinal (GI) or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.\n* Clinically significant inflammatory bowel disease, gastroparesis, severe disease, or surgery affecting the upper GI tract.\n* Any clinically important illness, medical/surgical procedure, or trauma.\n* Participants who have previously received elecoglipron within the last 3 months.","minimumAge":"18 Years","maximumAge":"55 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Elecoglipron Reference Formulation Dose A","description":"Elecoglipron tablets will be administered orally."},{"type":"DRUG","name":"Elecoglipron Test formulation 1 Dose A","description":"Elecoglipron tablets will be administered orally."},{"type":"DRUG","name":"Elecoglipron Reference Formulation Dose B","description":"Elecoglipron tablets will be administered orally."},{"type":"DRUG","name":"Elecoglipron Test formulation 1 Dose B","description":"Elecoglipron tablets will be administered orally."},{"type":"DRUG","name":"Elecoglipron Test formulation 2 Dose A","description":"Elecoglipron tablets will be administered orally."},{"type":"DRUG","name":"Elecoglipron Test formulation 2 Dose B","description":"Elecoglipron tablets will be administered orally."}],"primaryOutcomes":[{"measure":"Maximum observed drug concentration (Cmax)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Area under concentration-time curve from time 0 to infinity (AUCinf)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Time to reach maximum observed concentration (tmax)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Terminal elimination rate constant (λz)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Terminal elimination half-life (t1/2λz)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Apparent total body clearance (CL/F)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"},{"measure":"Apparent volume of distribution based on the terminal phase (Vz/F)","description":"To evaluate the PK of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"At pre-defined intervals from Day 1 to Day 15"}],"secondaryOutcomes":[{"measure":"Number of participants with adverse events (AEs)","description":"To assess the safety and tolerability of different formulations of elecoglipron following single oral administration in healthy participants.","timeFrame":"From screening (Day -28) up to follow-up visit (Day 18-Day 22)"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07723833"},{"nctId":"NCT07723924","title":"This is a Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Efficacy and Safety of 2 Weight-based Treatment Groups of Plecanatide Versus Placebo in Children and Adolescent Participants 6 to Less Than 18 Years of Age With FC","officialTitle":"A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Efficacy and Safety of Plecanatide in Children and Adolescents Age 6 to <18 Years of Age With Functional Constipation (FC)","summary":"The goal of this clinical trial is to learn if plecanatide can treat functional constipation in children and adolescents aged 6 to less than 18 years. It will also learn about the safety and pharmacokinetics of plecanatide in this population. The main questions it aims to answer are:\n\n* Does plecanatide increase the number of spontaneous bowel movements compared to placebo after 8 weeks of treatment?\n* What medical problems do participants experience when taking plecanatide? Researchers will compare low-dose plecanatide and high-dose plecanatide to placebo to see if plecanatide improves bowel movement frequency, stool consistency, and constipation-related symptoms.\n\nParticipants will:\n\n* Complete a screening period with daily electronic diary entries to record bowel movements, symptoms, and rescue medication use\n* Take plecanatide or placebo by mouth once daily for 8 weeks\n* Continue daily electronic diary entries throughout the study\n* Attend clinic visits for physical exams, laboratory tests, and assessments of symptoms and safety\n* Provide blood samples for pharmacokinetic and safety evaluations\n* Complete questionnaires about constipation symptoms and quality of life","detailedDescription":"This Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of plecanatide administered orally once daily in pediatric participants with functional constipation (FC). Approximately 180 participants will be enrolled at up to 30 investigational sites in the United States and randomized in a 1:1:1 ratio to receive low-dose plecanatide, high-dose plecanatide, or matching placebo. Randomization will be stratified by age group (6 to 11 years and 12 to less than 18 years) and sex.\n\nBackground and Rationale Functional constipation is a common condition in children and adolescents and is characterized by infrequent bowel movements, hard stool consistency, and associated symptoms such as straining and abdominal discomfort. Available treatment options in the pediatric population are limited, and there remains a need for additional therapies.\n\nPlecanatide is an orally administered guanylate cyclase-C (GC-C) agonist that acts locally in the gastrointestinal tract to increase intestinal fluid secretion and transit. Clinical studies in adults with chronic idiopathic constipation have demonstrated improvements in bowel movement frequency and stool consistency, as well as an acceptable safety profile. The current study is designed to evaluate plecanatide in a pediatric population using a weight-based dosing approach intended to achieve exposure levels comparable to those associated with efficacy in adults.\n\nStudy Design The study consists of three periods: a Screening/Baseline Period, an 8-week Treatment Period, and a Post-treatment Follow-up Period. The total duration of participation is approximately 14 weeks (98 days).\n\nDuring the Screening/Baseline Period (up to 28 days), participants and/or caregivers complete daily assessments using an electronic diary (eDiary) to record bowel movements, stool characteristics, and constipation-related symptoms. Data from the eDiary are used to establish baseline values and confirm eligibility prior to randomization.\n\nParticipants who meet all eligibility criteria are randomized on Day 1 and enter the Treatment Period. Study drug is administered once daily for 8 weeks. Participants are required to continue daily eDiary entries throughout the Treatment Period to capture bowel movement frequency, stool consistency, symptom severity, and use of rescue medication.\n\nFollowing completion of the Treatment Period, participants enter a 2-week Post-treatment Follow-up Period, during which eDiary assessments continue. A final study visit is conducted at the end of follow-up.\n\nTreatment and Randomization Participants are randomized via an interactive web-based system to receive low-dose plecanatide, high-dose plecanatide, or placebo. Dose assignment is based on treatment group and participant body weight at the time of randomization in order to achieve predefined weight-based dosing ranges.\n\nStudy drug is administered orally once daily, preferably in the morning, with or without food. Participants who are unable to swallow tablets may have the study drug administered in a suitable alternative form as described in the protocol.\n\nA rescue medication (bisacodyl) is provided for use if a participant has not had a bowel movement for at least 72 hours. Use of rescue medication is recorded in the eDiary and is subject to protocol-defined limitations.\n\nEfficacy Evaluations Efficacy evaluations are based primarily on data collected through the eDiary and participant-reported outcome (PRO) instruments administered at study visits.\n\nThe primary efficacy variable is the change from baseline in spontaneous bowel movement (SBM) frequency at Week 8. Secondary efficacy variables include responder endpoints based on SBM and complete spontaneous bowel movement (CSBM) frequency, stool consistency assessed using the Bristol Stool Form Scale (BSFS) or modified BSFS, and changes from baseline in constipation-related symptoms. Additional assessments include time to first bowel movement, use of rescue medication, and global and symptom-specific PRO measures.\n\nSafety Evaluations Safety is monitored throughout the study by assessment of adverse events (AEs), clinical laboratory parameters, vital signs, physical examinations, and electrocardiograms (ECGs).\n\nGastrointestinal events, including diarrhea, are of particular interest due to the mechanism of action of plecanatide. Criteria for dose interruption or discontinuation are specified in the protocol for participants experiencing clinically significant adverse events.\n\nTreatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events will be summarized descriptively by treatment group.\n\nPharmacokinetic Assessments Pharmacokinetic evaluations include measurement of plasma concentrations of plecanatide and its metabolite at specified time points following dosing. Given the minimal systemic absorption observed in prior studies, PK analyses are exploratory and are intended to further characterize exposure in the pediatric population.\n\nStatistical Considerations Approximately 30 participants per treatment group within each age cohort are planned. The sample size is considered sufficient for evaluation of the primary objective in this Phase 2b study.\n\nThe primary efficacy analysis will be performed on the intent-to-treat population using a mixed-effects model for repeated measures, including treatment group, time, and relevant baseline covariates. Secondary endpoints will be analyzed using appropriate statistical methods based on endpoint type.\n\nSafety analyses will be performed on the safety population and will be summarized descriptively.\n\nData Collection and Study Conduct Study data are collected using electronic case report forms (eCRFs) and participant eDiaries. Compliance with study procedures, including study drug administration and diary completion, is monitored throughout the study.\n\nThe study is conducted in accordance with the principles of Good Clinical Practice (GCP), applicable regulatory requirements, and institutional review board or ethics committee approval. Written informed consent and, where applicable, assent are obtained prior to participation.","peptideSlugs":["plecanatide"],"peptideNames":["Plecanatide"],"conditions":["Functional Constipation (FC)"],"keywords":["constipation","pediatric","functional constipation","chronic idiopathic constipation","children","plecanatide","trulance","FC","CIC","chronic constipation"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Bausch Health Americas, Inc.","slug":"bausch-health-americas-inc","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":180,"dates":{"start":"2026-06-01","primaryCompletion":"2027-10-18","completion":"2027-10-18","firstPosted":"2026-07-23","resultsPosted":null,"lastUpdated":"2026-07-23"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"AppleMedical Research Group, Inc","status":null,"city":"Miami","state":"Florida","country":"United States","latitude":25.77427,"longitude":-80.19366}],"eligibility":{"criteria":"Inclusion Criteria:• Male or female children and adolescents aged 6 to \\<18 years at time of consent.\n\n* Diagnosis of functional constipation (FC) based on Rome IV criteria for children/adolescents.\n* Participant and/or legally authorized representative able to provide informed consent/assent.\n* Participant/caregiver willing and able to comply with study procedures, including electronic diary (eDiary).\n* Completion of ≥5 out of 7 daily diary entries during each of the 2 baseline weeks.\n* Stable diet for at least 14 days prior to screening.\n* Females of childbearing potential must use highly effective contraception and have negative pregnancy tests.\n\nExclusion Criteria:\n\n* Weight \\<15 kg at screening/randomization.\n* History of anorectal malformations, neurological deficits, or anatomical abnormalities affecting bowel function.\n* Use of prohibited medications within 15 days prior to randomization (e.g., anticholinergics, 5-HT agents, opioids, other laxatives).\n* Use of any laxatives other than study-provided Dulcolax®.\n* Pregnant or breastfeeding participants.\n* Active eating disorder within the past 6 months.\n* Clinically significant medical conditions (hepatic, renal, gastrointestinal, endocrine, infectious) that may interfere with study.\n* Known hypersensitivity to plecanatide.\n* History of drug or alcohol abuse within 12 months.\n* Participation in another clinical trial within 30 days.\n* Non-compliance with eDiary requirements (\\<5/7 entries per week).\n* Use of rescue medication more than 2 days per week during baseline.\n* ≥3 spontaneous bowel movements (SBMs) per week during baseline.","minimumAge":"6 Years","maximumAge":"17 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"plecanatide","description":"Plecanatide is administered orally once daily for 8 weeks. Participants receive weight-based dosing corresponding to assigned treatment arm (low-dose or high-dose) to achieve target exposure ranges. Tablets may be taken with or without food and may be swallowed whole or administered in an alternative form if necessary, as specified in the protocol."},{"type":"DRUG","name":"Placebo","description":"Placebo tablets matching plecanatide in appearance are administered orally once daily for 8 weeks. Placebo is used to maintain blinding and is administered under the same conditions as active study drug."}],"primaryOutcomes":[{"measure":"Change From Baseline in Weekly Spontaneous Bowel Movement (SBM) Frequency at Week 8","description":"Spontaneous bowel movements (SBMs) are defined as bowel movements that occur without the use of rescue medication within the preceding 24 hours. Weekly SBM frequency will be calculated based on daily electronic diary entries. The endpoint is the change from baseline in the number of SBMs per week at Week 8.","timeFrame":"Baseline to week 8"}],"secondaryOutcomes":[{"measure":"Proportion of Participants Who Are SBM Responders at Week 8","description":"An SBM responder is defined as a participant who achieves an increase from baseline of ≥1 spontaneous bowel movement (SBM) per week. The proportion of responders will be assessed at Week 8 based on electronic diary data.","timeFrame":"week 8"},{"measure":"Change From Baseline in Weekly Complete Spontaneous Bowel Movement (CSBM) Frequency at Week 8","description":"Complete spontaneous bowel movements (CSBMs) are defined as SBMs associated with a sensation of complete evacuation. Weekly CSBM frequency will be calculated based on daily electronic diary entries. The endpoint is the change from baseline in the number of CSBMs per week at Week 8.","timeFrame":"Baseline to week 8"},{"measure":"Change From Baseline in Stool Consistency as Measured by the Bristol Stool Form Scale (BSFS) at Week 8","description":"Stool consistency will be assessed using the Bristol Stool Form Scale (BSFS) recorded in the electronic diary. Scores range from 1 (hard stools) to 7 (watery stools). The endpoint is the change from baseline in mean BSFS score at Week 8.","timeFrame":"Baseline to week 8"},{"measure":"Time to First Spontaneous Bowel Movement (SBM)","description":"Time to first spontaneous bowel movement (SBM) is defined as the time from first dose of study drug to the first SBM recorded in the electronic diary.","timeFrame":"up to 8 weeks"},{"measure":"Use of Rescue Medication Over 8 Weeks","description":"Rescue medication use is defined as the number of days participants use rescue medication (bisacodyl) due to lack of bowel movement. Use will be recorded daily in the electronic diary.","timeFrame":"Baseline and Weeks 1 through 8"},{"measure":"Incidence of Treatment-Emergent Adverse Events (TEAEs)","description":"A treatment-emergent adverse event (TEAE) is any adverse event that begins or worsens after the first dose of study drug through the end of the follow-up period.","timeFrame":"Up to 10 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07723924"},{"nctId":"NCT03363464","title":"Comparative Effectiveness of Empagliflozin in the US","officialTitle":"EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Study Program","summary":"Empagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor, was launched as a treatment for type 2 diabetes mellitus (T2DM) in the U.S. in August 2014. In contrast with several previous cardiovascular outcomes trials, which failed to demonstrate an association with a higher or a lower risk of cardiovascular outcomes associated with members of other recently marketed antidiabetic classes, the EMPA-REG OUTCOME trial has shown that patients at high cardiovascular risk randomized to empagliflozin vs. placebo, were associated with a reduced risk of hospitalization for heart failure, cardiovascular mortality, and all-cause mortality.\n\nHowever, these and other findings arising from an extensive clinical trial program aimed at evaluating the efficacy and safety profile for empagliflozin have yet to be demonstrated in a non-trial environment. This study aims to investigate the transferability of the effects demonstrated in dedicated randomized clinical studies to a broader population under real world conditions.","detailedDescription":null,"peptideSlugs":["glucagon"],"peptideNames":["Glucagon"],"conditions":["Diabetes Mellitus, Type 2"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Boehringer Ingelheim","slug":"boehringer-ingelheim","class":"INDUSTRY"},"collaborators":[{"name":"Eli Lilly","slug":"eli-lilly","class":"INDUSTRY"}],"status":{"raw":"COMPLETED","group":"completed","label":"Completed"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":230000,"dates":{"start":"2017-10-16","primaryCompletion":"2026-07-09","completion":"2026-07-09","firstPosted":"2017-12-06","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Bringham Women Hospital","status":null,"city":"Boston","state":"Massachusetts","country":"United States","latitude":42.35843,"longitude":-71.05977}],"eligibility":{"criteria":"Inclusion criteria:\n\n* Patients \\>= 18 years old for Marketscan and Optum, and \\>=65 years old for Medicare only\n* Patients initiating empagliflozin or a DPP-4 inhibitor within the study period. Initiation was defined as no use of SGLT-2 inhibitors (canagliflozin, dapagliflozin, ertugliflozin) or DPP-4 inhibitors in the previous 12 months.\n* Restriction to patients with a diagnosis of T2DM (ICD-9 Dx code of 250.x0 or 250.x2; ICD-10 Dx code of E11.x) in the 12 months prior to drug initiation.\n\nExclusion criteria:\n\n* Patients with missing or ambiguous age or sex information.\n* All patients who have less than 12 months of continuous registration in the database prior to initiation of empagliflozin or a DPP-4 inhibitor will be excluded.\n* Patients with type 1 diabetes mellitus (T1DM) defined as at least 1 inpatient or outpatient codes in the 12 months prior to drug initiation.\n* Secondary diabetes, and gestational diabetes in the 12 months prior to drug initiation\n* History of cancer in the 5 years prior to drug initiation\n* End-stage renal disease (ESRD) in the 12 months prior to drug initiation\n* HIV diagnosis or treatment in the 12 months prior to drug initiation\n* Organ transplant in the 12 months prior to drug initiation\n* Patients that were in nursing homes in the 12 months prior to drug initiation\n* Patients with concomitant SGLT-2 inhibitor and DPP-4 inhibitor initiation will also be excluded.\n* Patients initiating more than one DPP-4i on cohort entry date will additionally be excluded Additional exclusion criteria apply.","minimumAge":"18 Years","maximumAge":null,"sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Empagliflozin","description":"Empagliflozin"},{"type":"DRUG","name":"DPP-4 inhibitor","description":"dipeptidyl peptidase-4 inhibitor"},{"type":"DRUG","name":"GLP-1 receptor agonist","description":"Glucagon-like peptide-1 receptor agonist"}],"primaryOutcomes":[{"measure":"3-point major adverse cardiovascular events (MACE)","description":"i.e., non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular (CV) mortality; as well as each individual component:\n\n* Hospital admission for MI (for purposes of this individual component, fatal MI is included)\n* Hospital admission for stroke (for purposes of this individual component, fatal stroke is included)\n* CV mortality","timeFrame":"60 months"},{"measure":"Hospitalization for heart failure (specific, based on primary inpatient diagnosis code)","description":null,"timeFrame":"60 months"},{"measure":"Hospitalization for heart failure (broad, based on any inpatient diagnosis code)","description":null,"timeFrame":"60 months"},{"measure":"Modified MACE","description":"i.e., composite of MI, stroke or all-cause mortality","timeFrame":"60 months"},{"measure":"Composite of MI or stroke hospital admission for heart failure","description":null,"timeFrame":"60 months"},{"measure":"All-cause mortality","description":null,"timeFrame":"60 months"}],"secondaryOutcomes":[{"measure":"Coronary revascularization procedure","description":null,"timeFrame":"60 months"},{"measure":"Hospitalization for unstable angina","description":null,"timeFrame":"60 months"},{"measure":"Composite of MI, stroke, unstable angina hospitalization or coronary revascularization","description":null,"timeFrame":"60 months"},{"measure":"End-stage renal disease (ESRD)","description":null,"timeFrame":"60 months"},{"measure":"Bone fracture","description":null,"timeFrame":"60 months"},{"measure":"Diabetic ketoacidosis (Inpatient, primary position)","description":null,"timeFrame":"60 months"},{"measure":"Diabetic ketoacidosis (Inpatient, any position)","description":null,"timeFrame":"60 months"},{"measure":"Severe hypoglycemia","description":null,"timeFrame":"60 months"},{"measure":"Urinary tract cancers","description":null,"timeFrame":"60 months"},{"measure":"Lower-limb amputation","description":null,"timeFrame":"60 months"}],"publications":[{"pmid":"30955357","citation":"Patorno E, Pawar A, Franklin JM, Najafzadeh M, Deruaz-Luyet A, Brodovicz KG, Sambevski S, Bessette LG, Santiago Ortiz AJ, Kulldorff M, Schneeweiss S. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. Circulation. 2019 Jun 18;139(25):2822-2830. doi: 10.1161/CIRCULATIONAHA.118.039177. Epub 2019 Apr 8."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT03363464"},{"nctId":"NCT03796884","title":"Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer","officialTitle":"Phase II Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Bioactivity in Patients With Sporadic Colorectal Adenomas and With Colorectal Cancer","summary":"This phase II trial studies the how well linaclotide works in treating patients with stages 0-3 colorectal cancer. Linaclotide is a very small protein that binds to receptors on intestinal cells and makes them secrete water and salt.","detailedDescription":"PRIMARY OBJECTIVES:\n\nI. To determine whether, compared to placebo, linaclotide administered as a single oral daily dose x 7 days, induces a pharmacodynamics (PD) effect on cGMP levels, based on biopsy samples of adenomas or resected colorectal adenocarcinomas.\n\nSECONDARY OBJECTIVES:\n\nI. To compare Ki-67, guanylin levels and GUCY2C expression in adenomas and cancers versus normal tissue after exposure to linaclotide or placebo.\n\nII. To confirm the safety and tolerability of linaclotide in sporadic adenoma and cancer patients.\n\nTRANSLATIONAL OBJECTIVE:\n\nI. To assess the pharmacodynamic effect of linaclotide on pathway-specific biomarkers relevant to GUCY2C signaling (i.e. VASP phosphorylation), markers of mutant APC-beta-catenin signaling (beta-catenin levels, beta-catenin nuclear localization, axin levels, c-Myc levels, guanylin levels, PCNA expression), based on adenoma/cancer and normal mucosa biopsy samples obtained by endoscopy following linaclotide or placebo exposure.\n\nOUTLINE: Patients are randomized to 1 of 2 arms.\n\nARM I: Patients receive linaclotide orally (PO) daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.\n\nARM II. Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.\n\nAfter completion of study treatment, patients are followed up at day 14.","peptideSlugs":["linaclotide"],"peptideNames":["Linaclotide"],"conditions":["Colorectal Adenoma","Stage 0 Colorectal Cancer AJCC v8","Stage I Colorectal Cancer AJCC v8","Stage II Colorectal Cancer AJCC v8","Stage IIA Colorectal Cancer AJCC v8","Stage IIB Colorectal Cancer AJCC v8","Stage IIC Colorectal Cancer AJCC v8","Stage III Colorectal Cancer AJCC v8","Stage IIIA Colorectal Cancer AJCC v8","Stage IIIB Colorectal Cancer AJCC v8","Stage IIIC Colorectal Cancer AJCC v8"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University","slug":"sidney-kimmel-comprehensive-cancer-center-at-thomas-jefferson-university","class":"OTHER"},"collaborators":[{"name":"United States Department of Defense","slug":"united-states-department-of-defense","class":"FED"}],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":150,"dates":{"start":"2019-10-30","primaryCompletion":"2026-09-30","completion":"2026-09-30","firstPosted":"2019-01-08","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":3,"countries":["United States"],"locations":[{"facility":"Fox Chase Cancer Center","status":null,"city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University","status":null,"city":"Philadelphia","state":"Pennsylvania","country":"United States","latitude":39.95238,"longitude":-75.16362},{"facility":"VA Puget Sound Health Care Sysem","status":null,"city":"Seattle","state":"Washington","country":"United States","latitude":47.60621,"longitude":-122.33207}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* History of 1 or more sporadic colorectal adenoma on previous endoscopy (adenoma cohort) or stage 0-3 biopsy proven colorectal cancer (CRC) (colorectal cancer cohort) who are scheduled for a surgical procedure\n* Ability to understand and willingness to sign a written informed consent document and follow study procedures\n* Ability to swallow capsules without difficulty\n* Ability to maintain pill diaries\n* Willingness to employ adequate contraception for men and women of childbearing potential for the duration of the study. Acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status, and/or documentation of surgical sterilization\n* Participants must have no chronic, clinically severe health issues which, in the opinion of their physician or the research team, could preclude trial activities including the one week drug exposure phase\n\nExclusion Criteria:\n\n* History of gastroparesis\n* History of celiac disease\n* Inflammatory bowel disease (Crohn's disease, ulcerative colitis)\n* Microscopic colitis, including collagenous colitis\n* Has taken linaclotide within 30 days prior to consent\n* Any malignancy except colorectal cancer or any active radiotherapy or cytotoxic chemotherapy within the last 6 months of baseline. Participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator\n* Participants may not be receiving any other investigational agents, or be active participants in any clinical trials. If participants previously participated in a clinical trial, a 30 day washout period for the investigational drug is needed before the participant can be considered for this study\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to linaclotide\n* Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant or lactating women\n* History of bleeding/coagulation problems. Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin is acceptable\n* Any medical condition judged by the investigator to constitute a risk to safe participation\n* At risk for obstructing or near-obstructing mechanical gastrointestinal obstruction\n* Chronic use of anti-coagulants or non-NSAID anti-platelet agents will serve as an exclusion only when such medications cannot be safely discontinued before study related endoscopy or surgery","minimumAge":"18 Years","maximumAge":"80 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Linaclotide","description":"Given PO"},{"type":"OTHER","name":"Placebo","description":"Given PO"}],"primaryOutcomes":[{"measure":"Pharmacodynamics effect on cGMP levels","description":"Will compare cGMP levels in adenomas between study arms using a two-sample t-test (alpha=.05; two-sided) or Wilcoxon rank sum test.","timeFrame":"Up to 2 years, plus an additional 12 months for primary analysis"}],"secondaryOutcomes":[{"measure":"Incidence of adverse events (AEs)","description":"All participants will be evaluated for toxicity. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be used to summarize adverse events associated with linaclotide.","timeFrame":"From the time of first dose of linaclotide or placebo until resolution, if related to linaclotide, or through 30 days after occurrence"},{"measure":"Ki-67 expression","description":"Wilcoxon rank sum test will be used to compare Ki-67 expression in adenomas across arms.","timeFrame":"Up to 2 years"},{"measure":"GUCY2C expression","description":"Wilcoxon rank sum and Fisher's exact tests will be used to compare GUCY2C expression between study arms.","timeFrame":"Up to 2 years"},{"measure":"Guanylin levels","description":"Wilcoxon rank sum and Fisher's exact tests will be used to compare guanylin levels between study arms.","timeFrame":"Up to 2 years"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT03796884"},{"nctId":"NCT03884075","title":"Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)","officialTitle":"Non-Alcoholic Fatty Liver Disease, the Hepatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)","summary":"Background:\n\nIn non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help.\n\nObjective:\n\nTo find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide.\n\nEligibility:\n\nPeople with NAFLD and healthy volunteers ages 18 and older\n\nDesign:\n\nParticipants will be screened with:\n\nMedical history\n\nPhysical exam\n\nBlood tests\n\nImaging: A machine will take pictures of the participant s body.\n\nWithin 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes:\n\nBlood, urine, heart, and imaging tests\n\nFor NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue.\n\nParticipants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times.\n\nThe baseline visit concludes participation for healthy volunteers but NAFLD participants will contine.\n\nAbout 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection.\n\nParticipants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests.\n\nParticipants will inject semaglutide once a week at home.\n\nAt week 30, participants will stay in the clinic again and repeat the tests.\n\nParticipants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests.\n\n...","detailedDescription":"Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are leading causes of liver injury and are tightly associated with obesity, diabetes and the metabolic syndrome. Despite recent advances, there is still a considerable knowledge gap regarding the fundamental pathogenic mechanisms, and especially regarding the transition from benign steatosis to steatohepatitis. Although NAFLD reflects disordered energy metabolism in the liver, little information exists on the response of the human liver to the acute caloric load of a meal. We hypothesize, based on preliminary non-invasive results, that in patients with NAFLD, an oral carbohydrate load results in preferential de novo lipogenesis (due to selective insulin resistance) and generation of fatty acids (FA). We further hypothesize a spillover effect, wherein NASH patients have an impairment of the hepatic ability to esterify the load of FA to triglycerides (TG) compared to patients with steatosis, resulting in accumulation of lipotoxic intermediary metabolites.\n\nGLP-1 receptor agonists (GLP-1RA) have demonstrated significant benefit in the treatment of diabetes and obesity. Liraglutide was shown in a prospective trial to improve NASH histology and other GLP-1RA have shown benefit in secondary analyses, consistent with a class effect. However, response rates to GLP-1RA, as well as to other pharmacological interventions in NAFLD, have not exceeded 50%, and there are no adequate baseline predictors of response that could allow for selection of subjects for personalized treatment. Given that GLP-1RAs exert their main activity in the post-prandial state, it is plausible that post-prandial parameters may be more effective in predicting treatment response and can shed light on its mechanism.\n\nOur aims in this study are (1) to assess the hepatic response to an acute oral carbohydrate load; (2) to identify which baseline parameters can predict the clinical response of NAFLD patients to a course of semaglutide, a novel GLP-1RA.\n\nWe propose a non-randomized, single-center, pilot exploratory study in which 32 subjects with steatosis (12-20) or NASH (12-20) will initially undergo two liver biopsies, one in the fasting state and one performed 2 hours after an oral 75g glucose load (OGTT biopsy). Tissue samples obtained will be subjected to a comparative, paired analysis of gene expression, protein phosphorylation in key signaling pathways, composition of tissue lipid species and oxidative stress. Subjects will be treated with semaglutide (escalated to 1 mg/week) for 30 weeks in all subjects, and their clinical response will be assessed by ALT and 1H-Magnetic resonance spectroscopy and a final (3rd) liver biopsy. Clinical responders will be compared to non-responders with regards to their baseline fasting and post-prandial parameters, to identify predictors of response.\n\nThe human hepatic response to a meal has never been studied at the tissue level and the findings of this study are likely to generate important data and clarify some of the fundamental questions regarding mechanisms of injury and insulin resistance. Furthermore, our study aims at identifying predictors of response to GLP-1RA and allow for appropriate selection of subjects for this class of medications, as well as to shed light on mechanism of response.","peptideSlugs":["semaglutide"],"peptideNames":["Semaglutide"],"conditions":["Non-Alcoholic Steatohepatitis","Non-Alcoholic Fatty Liver Disease"],"keywords":["Non-Alcoholic Steatohepatitis (NASH)","Steatosis","Caloric Load"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","slug":"national-institute-of-diabetes-and-digestive-and-kidney-diseases-niddk","class":"NIH"},"collaborators":[{"name":"National Cancer Institute (NCI)","slug":"national-cancer-institute-nci","class":"NIH"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":104,"dates":{"start":"2019-07-24","primaryCompletion":"2026-08-31","completion":"2026-10-02","firstPosted":"2019-03-21","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institutes of Health Clinical Center","status":"RECRUITING","city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026}],"eligibility":{"criteria":"* INCLUSION CRITERIA:\n\n  1. Male or female Aged \\>= 18 years of age.\n  2. Histological evidence of hepatic steatosis on a liver biopsy within 12 months OR evidence of fatty liver disease, as documented by imaging (ultrasound, CT, MRI, MRI-PDFF, MR spectroscopy, or Fibroscan CAP \\>= 285 db/M25) within 12 months.\n  3. Estimated average alcohol consumption \\< 30 g/d for men or \\< 20 g/d for women in the 6 months prior to enrollment and no binge-drinking behavior.\n  4. Ability of subject to understand and the willingness to sign a written informed consent document.\n\nAdditional Inclusion Criteria for Treatment Phase\n\n1. Presence of NAFLD (steatosis grade greater than or equal to 1 on NASH-CRN scoring scale) on baseline admission liver biopsy.\n2. Liver fat content greater than or equal to 10% by 1H-MRS on initial admission.\n\nEXCLUSION CRITERIA:\n\n1. Pregnant or breast-feeding\n2. Chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who were treated successfully for HCV and achieved sustained virological response can be eligible for enrollment \\> 18 months after treatment cessation. Patients receiving antiviral therapy are ineligible.\n3. HIV infection.\n4. Concomitant liver disease such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson s disease, alpha-1 antitrypsin deficiency, hereditary hemochromatosis.\n5. Presence of definite or probable drug-induced liver injury. In the case of lipid-lowering, anti-hypertensive or anti-diabetic medications that are suspected to cause aminotransferase elevation, patients will be eligible if treatment is associated with stable enzyme levels for at least 6 months.\n6. Decompensated advanced liver disease, defined as direct bilirubin \\> 0.5 g/dL, PT \\> 18 , albumin \\< 3 g/dL, MELD score \\> 12 (applicable only in patients without Gilbert s syndrome), or history of ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis or liver transplant\n7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen\n8. Uncontrolled hypo- or hyperthyroidism.\n9. Thyroid nodules with ultrasonographic features suggestive of an increased risk of thyroid cancer per radiologist reporting (hypoechoic, microcalcifications, twinkling on B flow imaging, central vascularity, irregular margins, incomplete halo, nodule taller than wide and documented enlargement of a nodule), or nodules associated with an abnormal TSH (0.4 to 5 mU/L).\n10. Active coronary artery disease, defined as persistent angina pectoris, reversible ischemia on cardiac stress test or imaging, or the presence of significant coronary artery disease on imaging or catheterization. Patients with coronary artery disease that was treated by angioplasty or bypass surgery may be eligible if they have no evidence of active disease \\>= 1 year after intervention, can safely stop antiplatelet and anticoagulant medications before the performance of invasive procedures, and have adequate ventricular function as assessed by echocardiography or cardiology consultation. These patients will require cardiology consultation and clearance prior to enrollment.\n11. Congestive heart failure.\n12. Chronic kidney disease, with creatinine clearance \\< 60 ml/min or eGFR \\< 60/ml/min/m(2).\n13. Uncontrolled diabetes mellitus with HbA1c \\> 9% will exclude subjects. Patients with diabetes may be enrolled only if they have HbA1c \\<=9%, have been on stable therapy with lifestyle and/or metformin for at least 3 months prior to enrollment, and are not foreseen to require change of antidiabetic medication or dose during the trial.\n14. Use of insulin, sulfonylurea agents, thiazolidinediones, SGLT2 inhibitors, GLP-1 receptor agonists or DPP-4 inhibitors unless discontinued greater than or equal to 3 months before enrollment.\n15. Contraindication or inability to perform a liver biopsy.\n\n    1. Patients with coagulopathy (PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of the normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (\\< 70,000), abnormal bleeding time or platelet dysfunction. Antiplatelet agents taken for cardiovascular prevention will not exclude patients, unless they cannot be stopped safely for the performance of a liver biopsy.\n    2. Hemoglobin level \\< 11 g/dL\n16. Contraindications to MRI (heart pacemakers, unless MRI safe, insulin pumps, implanted hearing aids, neurostimulators, intracranial metal clips, metallic bodies in the eye, metal hip replacements, sutures, extreme anxiety or fear of small spaces.)\n17. History of gastric bypass or other bariatric surgery, partial or complete gastrectomy and known maldigestion or malabsorption.\n18. Treatment with orlistat.\n19. Patients with uncontrolled eating disorders including anorexia and bulimia nervosa.\n20. Patients with proliferative diabetic retinopathy.\n21. Use of medications or supplements to treat NAFLD (approved or unapproved) unless withdrawn greater than or equal to 3 months prior to enrollment or taken at a stable dose for greater than or equal to 6 months.\n22. Patients who had a liver biopsy performed less than or equal to 2 years before enrollment, unless they are willing to undergo all of the trial biopsies, knowing that these biopsies are purely for research and are not clinically indicated. This will be clearly documented in the patients charts prior to enrollment.\n23. Inability or unwillingness to receive subcutaneous injections.\n24. Known or suspected allergy to trial medication(s), excipients, or related products.\n25. Alcohol or substance abuse within the past 12 months.\n26. For women of childbearing potential, breast-feeding, pregnancy or inability or unwillingness to practice contraception for the duration of the study.\n27. Personal or first-degree family member with history of medullary thyroid carcinoma or subjects with known multiple endocrine neoplasia syndrome type 2 (MEN-2).\n28. Actively pursuing an intensive weight loss regiment, aimed at losing \\> 10% of current body weight, by following a different diet or exercise regimen over the study time period or recent (\\<3 months) significant weight loss (\\>10%).\n29. The receipt of any investigational drug within 3 months prior to enrollment in this trial.\n30. Assessment by the principal investigator that the subject will be unlikely to complete the study procedures, or that enrollment puts the subject at a significant risk unspecified by the criteria above.\n\nINCLUSION CRITERIA for Healthy Volunteers (arm C)\n\n1. Male or female Aged greater than or equal to 18 years of age.\n2. No evidence of hepatic steatosis by imaging or histology.\n3. No history of known liver disease.\n4. Individuals on regular systemic medications may be considered eligible, and their eligibility will be determined by the principal investigator.\n5. BMI less than or equal to 25 kg/m2\n6. Non-diabetic.\n7. Normal transaminases (ALT less than or equal to 31 U/L for men or less than or equal to 19 U/L for women, and AST less than or equal to 30 U/L).\n8. Fasting glucose less than or equal to 95 mg/dL.\n9. Ability of subject to understand and the willingness to sign a written informed consent document.\n\nEXCLUSION CRITERIA for Healthy Volunteers (arm C)\n\n1. Pregnant or breastfeeding\n2. Excessive alcohol consumption, defined as an average alcohol consumption over \\> 1 drink per day over the past month\n3. Assessment by the principal investigator that the subject is unsuitable for participation in the study or that enrollment puts the subject at significant risk.","minimumAge":"18 Years","maximumAge":"100 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"Semaglutide","description":"Semaglutide injection once weekly"}],"primaryOutcomes":[{"measure":"Histological Improvement","description":"\\>= point decrease in NAFLD activity score (range 0-8, high scores indicate more activity)","timeFrame":"30 weeks"},{"measure":"Clinical Improvement","description":"Reduction of liver fat content (measure with 1H-magnetic resonance spectroscopy) by \\>= 25% and reduction of ALT by \\>=25% or normalization of ALT","timeFrame":"30 weeks"},{"measure":"Change in hepatic gene expression","description":"Change in hepatic gene expression for biopsies performed at baseline and 2 hours after an oral 75g glucose load","timeFrame":"2 hours after an oral 75g glucose load"}],"secondaryOutcomes":[],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT03884075"},{"nctId":"NCT05202353","title":"A Study in People With Obesity to Test the Effects of BI 456906 Compared With Semaglutide on Glucagon Receptor Activity in the Liver","officialTitle":"Open-label, Randomised, 4 Parallel-group, Phase I Clinical Trial to Investigate BI 456906 Occupancy of Glucagon Receptors in Liver and Glucagon-like Peptide 1 Receptors in Pancreas in Comparison With Semaglutide After Administration of Radiolabeled Tracer in Male and Female Subjects With Obesity Using PET and MRI","summary":"This study is open to adults with obesity. People with a body mass index (BMI) in the range from 30 to 40 kg/m2 and a body weight of 70 to 150 kg can participate in the study. The purpose of this study is to find out whether treatment with a medicine called BI 456906 changes the occupancy of receptors in the liver and in the pancreas. These receptors are involved in appetite and weight regulation. To measure the occupancy of these receptors, doctors use injectable tracers. Doctors visualise the binding of the tracers to these receptors with imaging methods.\n\nParticipants are put into 4 groups randomly, which means by chance. 2 groups get BI 456906 and 2 groups get semaglutide. Semaglutide is an approved medicine for body weight reduction. For 17 weeks, participants get injections under the skin. They either get BI 456906 twice a week or semaglutide once a week. The injected doses increase in small steps. Before and after 17 weeks of treatment, the receptor occupancy is determined.\n\nParticipants are in the study for up to 6 months. At the beginning and at the end of the treatment participants stay at the study site with an overnight stay. At the beginning, the study staff trains participants how to inject the study treatment at home. Participants who get BI 456906 visit the study site 18 times and have 19 visits at home. Participants who get semaglutide visit the study site 15 times and have 6 home visits. The doctors also regularly check participants' health and take note of any unwanted effects.","detailedDescription":null,"peptideSlugs":["semaglutide","survodutide","glucagon"],"peptideNames":["Semaglutide","Survodutide","Glucagon"],"conditions":["Obesity"],"keywords":[],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Boehringer Ingelheim","slug":"boehringer-ingelheim","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"ACTIVE_NOT_RECRUITING","group":"active","label":"Active, not recruiting"},"phases":{"raw":["PHASE1"],"slugs":["phase-1"],"labels":["Phase 1"],"label":"Phase 1","highest":1},"studyType":"INTERVENTIONAL","enrollment":29,"dates":{"start":"2024-10-01","primaryCompletion":"2026-12-02","completion":"2027-01-01","firstPosted":"2022-01-21","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":1,"countries":["Netherlands"],"locations":[{"facility":"Amsterdam UMC, location VUMC","status":null,"city":"Amsterdam","state":null,"country":"Netherlands","latitude":52.37403,"longitude":4.88969}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests\n* Age of 18 to 65 years (inclusive)\n* Body mass index (BMI) of ≥ 30 and ≤ 40 kg/m2 and body weight ≥70 kg and ≤150 kg\n* Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation\n* Women of childbearing potential (WOCBP) must be willing and able to use two forms of effective contraception where at least one form is a highly effective method of birth control per International Council for Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly\n\nExclusion Criteria:\n\n* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator\n* Resting heart rate \\> 100 beats per minute (bpm) and/or systolic blood pressure ≥ 160 millimetre of mercury (mmHg) and/or diastolic blood pressure ≥95 mmHg at screening.\n* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance. Subjects with the following abnormal values are not eligible for the trial participation:\n\n  * Low-density lipoprotein (LDL) \\> 160 mg/dL (4.15 mmol/L)\n  * total cholesterol \\>240 mg/dL (6.22 mmol/L)\n  * triglyceride \\>200 mg/dL (2.26 mmol/L)\n  * blood glucose \\> 126 mg/dl (\\>7 mmol/L) fasting and/or glycated haemoglobin (HbA1c) \\>6.5% (\\>48 mmol/mol)\n* Any evidence of a concomitant disease assessed as clinically relevant by the investigator. Subjects with type 1 and type 2 diabetes mellitus are not eligible for the trial\n* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator\n* Diseases of the central nervous system (including but not limited to any kind of seizures), and other relevant neurological or psychiatric disorders\n* History of relevant orthostatic hypotension, fainting spells, or blackouts\n* Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, manifest hypo- or hyperthyroidism at Visit 1\n\nFurther criteria apply","minimumAge":"18 Years","maximumAge":"65 Years","sex":"ALL","healthyVolunteers":true},"interventions":[{"type":"DRUG","name":"BI 456906","description":"BI 456906"},{"type":"DRUG","name":"Semaglutide","description":"Semaglutide"}],"primaryOutcomes":[{"measure":"Percentage of glucagon (GCG) receptors occupancy in the liver using Positron emission tomography (PET) imaging at End of Treatment (EOT) visit","description":null,"timeFrame":"up to Week 17"}],"secondaryOutcomes":[{"measure":"Percentage of glucagon-like Peptide 1 (GLP-1) receptors occupancy in the pancreas using PET imaging at EOT visit","description":null,"timeFrame":"up to Week 17"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT05202353"},{"nctId":"NCT06164795","title":"Sequential Therapies After Osteoanabolic Treatment","officialTitle":"Efficacy of Sequential Therapies After Osteoanabolic Treatment in Postmenopausal Women With Severe Osteoporosis: the Sequential Treatment After Romosozumab and Teriparatide/Abaloparatide (START) Study","summary":"12-month prospective, open-label, multicenter, international, observational study evaluating sequential treatments after osteoanabolics","detailedDescription":"Caucasian women with severe postmenopausal osteoporosis who have completed their course with romosozumab or a PTH analog will be assigned to one of the following 3 options: i) zoledronate 5mg infusion or ii) denosumab subcutaneous injections or iii) teriparatide or abaloparatide (for those previously treated with romosozumab) or romosozumab (for those previously treated with teriparatide or abaloparatide).\n\nEndpoints: Primary: BMD changes at the lumbar spine at 12 months. Secondary: i) BMD changes at the non-dominant femoral neck and total hip at 12 and 24 months; ii) changes at levels of bone turnover markers throughout the study; iii) incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral","peptideSlugs":["teriparatide","abaloparatide"],"peptideNames":["Teriparatide","Abaloparatide"],"conditions":["Osteoporosis, Postmenopausal"],"keywords":[],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"424 General Military Hospital","slug":"424-general-military-hospital","class":"OTHER"},"collaborators":[{"name":"Laikο General Hospital, Athens","slug":"laik-general-hospital-athens","class":"OTHER"},{"name":"251 Hellenic Air Force & VA General Hospital","slug":"251-hellenic-air-force-and-va-general-hospital","class":"OTHER"},{"name":"KAT General Hospital","slug":"kat-general-hospital","class":"OTHER"},{"name":"Campus Bio-Medico University","slug":"campus-bio-medico-university","class":"OTHER"},{"name":"Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Milano","slug":"fondazione-irccs-ca-granda-ospedale-maggiore-policlinico-milano","class":"UNKNOWN"},{"name":"Azienda Ospedaliero Universitaria, Santa Maria della Misericordia di Udine, Italy","slug":"azienda-ospedaliero-universitaria-santa-maria-della-misericordia-di-udine-italy","class":"OTHER"},{"name":"University of Siena","slug":"university-of-siena","class":"OTHER"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":[],"slugs":[],"labels":[],"label":"Not applicable","highest":0},"studyType":"OBSERVATIONAL","enrollment":150,"dates":{"start":"2023-11-25","primaryCompletion":"2027-06-01","completion":"2027-12","firstPosted":"2023-12-11","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":8,"countries":["Greece","Italy"],"locations":[{"facility":"251 Airforce & VA General Hospital","status":"RECRUITING","city":"Athens","state":null,"country":"Greece","latitude":37.98376,"longitude":23.72784},{"facility":"First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens","status":"RECRUITING","city":"Athens","state":null,"country":"Greece","latitude":37.98376,"longitude":23.72784},{"facility":", KAT General Hospital","status":"RECRUITING","city":"Athens","state":null,"country":"Greece","latitude":37.98376,"longitude":23.72784},{"facility":"424 General Military Hospital","status":"RECRUITING","city":"Thessaloniki","state":null,"country":"Greece","latitude":40.64072,"longitude":22.93493},{"facility":"Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico","status":"RECRUITING","city":"Milan","state":null,"country":"Italy","latitude":45.46427,"longitude":9.18951},{"facility":"Campus Bio-Medico University","status":"RECRUITING","city":"Roma","state":null,"country":"Italy","latitude":44.99364,"longitude":11.10642},{"facility":"Department of Medicine, Surgery and Neurosciences, University of Siena","status":"RECRUITING","city":"Siena","state":null,"country":"Italy","latitude":43.31822,"longitude":11.33064},{"facility":"University-Hospital S. Maria della Misericordia","status":"RECRUITING","city":"Udine","state":null,"country":"Italy","latitude":46.0693,"longitude":13.23715}],"eligibility":{"criteria":"Inclusion Criteria:\n\n• Postmenopausal women treated with severe osteoporosis completing their course with romosozumab or teriparatide\n\nExclusion Criteria:\n\n* a bone disease other than postmenopausal osteoporosis\n* use of medications other than romosozumab or teriparatide affecting bone metabolism during the last 12 months before entering the study\n* creatinine clearance \\<60 mL/min/1.73 m2\n* liver failure\n* any type of cancer\n* uncontrolled endocrine diseases\n* serum 25-hydroxy vitamin D (25-OHD) concentrations lower than 20 ng/mL (50 nmol/L)\n* hypersensitivity to denosumab or zoledronate or teriparatide or romosozumab or any of the excipients","minimumAge":"50 Years","maximumAge":"85 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Zoledronate","description":"intravenous infusion"},{"type":"DRUG","name":"Denosumab","description":"subcutaneous injection"},{"type":"DRUG","name":"Teriparatide","description":"subcutaneous injection"},{"type":"DRUG","name":"Romosozumab","description":"subcutaneous injection"},{"type":"DRUG","name":"Abaloparatide Injection (80 mcg)","description":"daily subcutaneous injection"}],"primaryOutcomes":[{"measure":"lumbar spine bone mineral density","description":"bone mineral density changes at the lumbar spine at 12 months measured by dual-energy absorptiometry (DXA)","timeFrame":"baseline to 12 months"}],"secondaryOutcomes":[{"measure":"femoral neck bone mineral density","description":"bone mineral density changes at the femoral neck at 12 months measured by dual-energy absorptiometry (DXA)","timeFrame":"baseline to 12 months"},{"measure":"total hip bone mineral density","description":"bone mineral density changes at the total hip at 12 months measured by dual-energy absorptiometry (DXA)","timeFrame":"baseline to 12 months"},{"measure":"P1NP","description":"bone turnover (formation) marker","timeFrame":"baseline, 3 months, 6 months, 12 months"},{"measure":"CTx","description":"bone turnover (resorption) marker","timeFrame":"baseline, 3 months, 6 months, 12 months"},{"measure":"Fractures","description":"incident fractures: vertebral (clinical and morphometric identified on VFA scans) and non-vertebral","timeFrame":"12 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06164795"},{"nctId":"NCT06502990","title":"Open-label Study to Evaluate Metreleptin in Children Under 6 Years of Age With Generalised Lipodystrophy","officialTitle":"Open-label, Phase 3b Study to Evaluate Effectiveness, Safety and Pharmacokinetic Parameters of Metreleptin in Patients Under 6 Years of Age With Generalised Lipodystrophy and Associated Diabetes Mellitus and/or Hypertriglyceridaemia","summary":"This is an open-label, Phase 3b study to evaluate effectiveness, safety and pharmacokinetic parameters of metreleptin in patients under 6 years of age with generalised lipodystrophy and associated diabetes mellitus and/or hypertriglyceridaemia","detailedDescription":null,"peptideSlugs":["metreleptin"],"peptideNames":["Metreleptin"],"conditions":["Generalized Lipodystrophy"],"keywords":["Metreleptin"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Amryt Pharma","slug":"amryt-pharma","class":"INDUSTRY"},"collaborators":[],"status":{"raw":"TERMINATED","group":"terminated","label":"Terminated"},"phases":{"raw":["PHASE3"],"slugs":["phase-3"],"labels":["Phase 3"],"label":"Phase 3","highest":3},"studyType":"INTERVENTIONAL","enrollment":1,"dates":{"start":"2025-05-23","primaryCompletion":"2026-02-11","completion":"2026-02-11","firstPosted":"2024-07-16","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":12,"countries":["Belgium","France","Germany","Italy"],"locations":[{"facility":"UZ Leuven","status":null,"city":"Leuven","state":"Leuven","country":"Belgium","latitude":50.87959,"longitude":4.70093},{"facility":"Hôpital Necker - Enfants Malades","status":null,"city":"Paris","state":"Paris","country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Universitaire Robert-Debre","status":null,"city":"Paris","state":null,"country":"France","latitude":48.85341,"longitude":2.3488},{"facility":"Universitätsklinikum Hamburg-Eppendorf","status":null,"city":"Hamburg","state":"Free and Hanseatic City of Hamburg","country":"Germany","latitude":53.55073,"longitude":9.99302},{"facility":"Universitaetsklinikum Ulm - Klinik fuer Kinder- und Jugendmedizin","status":null,"city":"Ulm","state":"Ulm","country":"Germany","latitude":48.39841,"longitude":9.99155},{"facility":"IRCCS Ospedale Pediatrico Bambino Gesù","status":null,"city":"Chieti","state":"Chieti","country":"Italy","latitude":42.34827,"longitude":14.16494},{"facility":"Azienda Ospedaliera Universitaria \"Federico II\"","status":null,"city":"Naples","state":"Naples","country":"Italy","latitude":40.85216,"longitude":14.26811},{"facility":"Azienda Ospedaliero Universitaria Maggiore della Carità di Novara","status":null,"city":"Novara","state":"Novara","country":"Italy","latitude":45.44694,"longitude":8.62118},{"facility":"Azienda Ospedaliero-Universitaria di Parma","status":null,"city":"Parma","state":"Parma","country":"Italy","latitude":44.79935,"longitude":10.32618},{"facility":"Azienda Ospedaliero Universitaria Pisana","status":null,"city":"Pisa","state":"Pisa","country":"Italy","latitude":43.70853,"longitude":10.4036},{"facility":"IRCCS Ospedale Pediatrico Bambino Gesù","status":null,"city":"Rome","state":"Rome","country":"Italy","latitude":41.89193,"longitude":12.51133},{"facility":"Ospedale Filippo Del Ponte Varese - ASST Sette Laghi","status":null,"city":"Varese","state":"Varese","country":"Italy","latitude":45.82058,"longitude":8.82511}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Confirmed diagnosis of Generalised Lipodystrophy\n* Metreleptin treatment naive\n\nExclusion Criteria:\n\n* Weight \\<9 kg at Screening (Visit 1)","minimumAge":null,"maximumAge":"5 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Metreleptin","description":"Metreleptin is a recombinant human leptin analog that is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency"}],"primaryOutcomes":[{"measure":"Percent change from baseline in fasting serum TG levels at Month 12 for subjects with fasting TG levels ≥2.3 mmol/L (200 mg/dL) at baseline","description":"To evaluate the effectiveness of metreleptin in patients under 6 years of age with GL and associated diabetes mellitus and/or hypertriglyceridaemia","timeFrame":"12 months"},{"measure":"Absolute change from baseline in glycated haemoglobin (HbA1c) at Month 12 for subjects with HbA1c ≥6.5% at baseline","description":"To evaluate the effectiveness of metreleptin in patients under 6 years of age with GL and associated diabetes mellitus and/or hypertriglyceridaemia","timeFrame":"12 months"}],"secondaryOutcomes":[{"measure":"Proportion of subjects of those with Baseline HbA1c ≥6.5% achieving target actual decreases of at least 0.5%, 1%, 1.5%, 2% absolute decrease in HbA1c or HbA1c <6.5% or HbA1c <5.7% at Month 12","description":"To evaluate the efficacy of metreleptin treatment in patients with GL","timeFrame":"12 months"},{"measure":"Proportion of subjects of those with Baseline HbA1c ≥5.7% achieving target actual decreases of at least 0.5%, 1%, 1.5%, 2% absolute decrease in HbA1c or HbA1c <5.7% at Month 12","description":"To evaluate the efficacy of metreleptin treatment in patients with GL","timeFrame":"12 months"},{"measure":"Proportion of subjects of those with fasting serum TG ≥ 1.7 mmol/L (150 mg/dL) achieving target actual decreases from baseline of at least 15%, 20%, 25%, 30%, 35%, 40% at Month 12","description":"To evaluate the efficacy of metreleptin treatment in patients with GL","timeFrame":"12 months"},{"measure":"Proportion of subjects of those with fasting serum TG ≥ 2.3 mmol/L (200 mg/dL) achieving target actual decreases from baseline of at least 15%, 20%, 25%, 30%, 35%, 40% at Month 12","description":"To evaluate the efficacy of metreleptin treatment in patients with GL","timeFrame":"12 months"},{"measure":"Change from baseline in liver volume and liver span as assessed by ultrasound at each post-baseline visit through Month 12","description":"To evaluate the efficacy of metreleptin treatment in patients with GL","timeFrame":"12 months"},{"measure":"Incidence of, treatment emergent adverse events (TEAEs), serious adverse events (SAEs), treatment related adverse events (AEs), AEs of special interest (AESIs) and AEs leading to study drug discontinuation","description":"To assess safety and tolerability of metreleptin","timeFrame":"12 months"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT06502990"},{"nctId":"NCT07046819","title":"Tirzepatide in MetALD","officialTitle":"A Randomized, Double-Blind, Placebo-Controlled, Flexible Dose Phase 2 Study of Efficacy and Safety of Tirzepatide in Individuals With Alcohol Use Disorder and Metabolic Alcohol-associated Liver Disease","summary":"Background:\n\nPeople with alcohol use disorder (AUD) often develop metabolic alcohol-associated liver disease (MetALD). MetALD is a term for the heart, liver, obesity, and other issues that can accompany AUD. MetALD can be fatal. An approved weight management drug (Tirzepatide) may be able to help people with AUD and MetALD control their alcohol intake.\n\nObjective:\n\nTo test Tirzepatide in people with AUD and MetALD.\n\nEligibility:\n\nPeople aged 21 years and older with AUD and MetALD.\n\nDesign:\n\nParticipants will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They will have a Fibroscan: This test uses ultrasound to measure how stiff the liver is. They will answer questions about their alcohol drinking, eating habits, and mental health. Participants may opt to have imaging scans of their brain and liver.\n\nThese tests will be repeated in a baseline visit. This visit will take up to 6 hours.\n\nTirzepatide is injected under the skin once a week for 12 weeks. Participants will visit the clinic to receive each injection. Some participants will get a placebo. A placebo is given just like a Tirzepatide injection but contains no medicine. The physical exam and other tests will be repeated during clinic visits. The Fibroscan will be repeated every 2 weeks during the study. Each weekly visit will take up to 3 hours.\n\nAll tests will be repeated on the last visit. These tests will include the imaging scans and Fibroscan. Participants will learn about treatment options for AUD; they will be given recommendations on ways to reduce alcohol intake. This visit will take up to 6 hours.","detailedDescription":"STUDY DESCRIPTION:\n\nThe GLP-1/GIP receptor dual agonist tirzepatide has been recently shown to reduce HbA1c in adults with Type 2 diabetes, achieve weight reduction in adults with obesity and reduce metabolic dysfunction associated steatohepatitis. In addition, some data suggest beneficial effects on drinking behaviors. This study will evaluate the efficacy and safety of tirzepatide as a novel treatment for alcohol use disorder (AUD) and metabolic alcohol-associated liver disease (MetALD).\n\nWe hypothesize that tirzepatide will be well tolerated and safe in this new target population and that tirzepatide will achieve reduction in alcohol use, metabolic improvement and attenuate alcohol-induced liver steatosis.\n\nOBJECTIVES:\n\nPrimary Objective:\n\nThe primary objective is to assess the efficacy of tirzepatide in individuals with AUD/MetALD.\n\nSecondary/Exploratory Objectives:\n\nSecondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage, inflammation, neuropsychiatric outcomes, drinking behaviors, epigenetic age acceleration, brain metabolites, and safety.\n\nENDPOINTS:\n\nPrimary endpoints:\n\n\\- co-primary endpoint: metabolic improvement from baseline as measured by percentage reduction of body weight and reduction in liver steatosis from baseline as measured by percentage reduction in Fibroscan controlled attenuation parameter (CAP) score.\n\nSecondary endpoints:\n\n* Reduction in liver steatosis from baseline as measured by MRI spectroscopy\n* Reduction in MRI visceral fat from baseline\n* Reduction in liver enzymes (ALT, AST, GGT) from baseline\n* Reduction in drinking behaviors/cravings from baseline\n* Reduction in one WHO risk drinking level\n\nSecondary safety endpoints:\n\n\\- Safety and tolerability\n\nExploratory endpoints:\n\n* Effects on biomarkers (i.e. Il-6, FGF21, epigenetic and genetic markers, proteomics, metabolomics)\n* Effects on depression and anxiety measures\n* Effects on epigenetic age acceleration\n* Changes in brain metabolites as measured by MRI spectroscopy\n* Changes in resting state functional connectivity","peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Metabolic Alcohol-associated Liver Disease","Alcohol Use Disorder"],"keywords":["BMI","Weight","Alcohol","Metabolism"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"National Institute on Alcohol Abuse and Alcoholism (NIAAA)","slug":"national-institute-on-alcohol-abuse-and-alcoholism-niaaa","class":"NIH"},"collaborators":[],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE2"],"slugs":["phase-2"],"labels":["Phase 2"],"label":"Phase 2","highest":2},"studyType":"INTERVENTIONAL","enrollment":120,"dates":{"start":"2026-06-11","primaryCompletion":"2026-07-30","completion":"2026-07-30","firstPosted":"2025-07-02","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"National Institutes of Health Clinical Center","status":"RECRUITING","city":"Bethesda","state":"Maryland","country":"United States","latitude":38.98067,"longitude":-77.10026}],"eligibility":{"criteria":"* INCLUSION CRITERIA\n\nTo be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Age 21 or older\n2. Ability to provide written informed consent\n3. Females: Negative urine pregnancy test, not currently breastfeeding, agree to abstain or use accepted form of contraception including use of oral contraceptives and an additional barrier method of contraceptive such as condoms; use of an approved IUD or other longacting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s)\n4. Males: Agree to abstain or use accepted form of contraception, such as condoms.\n5. Diagnosis of AUD as confirmed by MINI\n6. Current alcohol use as assessed via the TLFB (\\>14 standard drinks per week for males and \\>7 standard drinks per week for females on average for the last 8 weeks)\n7. Liver steatosis as determined by Fibroscan (CAP score \\>240) at screening\n8. BMI \\>= 25 and \\<40 kg/m\\^2\n9. metALD as defined by at least one out of 5 criteria at screening:\n\n   1. BMI \\>= 25 and \\<40 kg/m\\^2\n   2. Fasting serum glucose \\>= 5.6mmol/L \\[100mg/dL\\] or HbA1c \\>=5.7%\n   3. Blood pressure \\>=130/85 or specific antihypertensive drug treatment\n   4. Plasma triglycerides \\>=1.70mmol/L \\[150mg/dL\\] or lipid lowering treatment\n   5. Plasma HDL-cholesterol less than 1.0mmol/L \\[40mg/dL\\] or lipid lowering treatment\n\nEXCLUSION CRITERIA\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Treatment seeking for alcohol use disorder\n2. History of a serious hypersensitivity reaction to GLP-1RA/GIPRA\n3. Current/past use of GLP-1RA/GIPRA within the last 3 months\n4. Clinically significant and/or unstable cardiovascular disease over the past 12 months\n5. History of diabetes mellitus or blood hemoglobin A1c (HbA1c) \\>= 6.5 % at screening\n6. Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening, history of cirrhosis, esophageal varices\n7. Subjects with platelets count of less than 110,000/ mm\\^3\n8. Alanine aminotransferase or aspartate aminotransferase exceeding 5 times the upper limit of normal levels at screening\n9. Bilirubin 2x UNL or Creatinine \\> 2 mg/dL at screening\n10. Patients with coagulopathy defined as INR \\>1.5, prothrombin time prolonged by \\> 3s, and/or platelets \\<75,000 / mm\\^3 at screening\n11. Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at screening\n12. Chronic renal failure as estimated by glomerular filtration rate (GFR) \\< 60mL/min/1.73 m\\^2 at screening\n13. History of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)\n14. History of previous bariatric surgery or transplant surgery\n15. Patients with significant hematologic abnormalities, as defined by hemoglobin \\< 8g/dL and/or white blood count \\<1500 cells/microL\n16. Current or prior history of any clinically significant disease, including, seizure disorder, epilepsy, alcohol related seizures within 12 months of screening, uncontrolled endocrine disease, hemorrhagic stroke, cancer within the past 5 years or any other significant abnormality identified at the time of screening that, in the judgment of the investigator or study clinician, would preclude safe completion of the study\n17. Use of any medications that interfere with tirzepatide\n18. Use of the following medications with glucose lowering properties in the last 30 days: GLP-1RA, GLP-1RA/GIPRA, insulin, metformin, sulfonylurea, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors\n19. Use of the following medications: Any medication that requires intramuscular administration injections. Systemic corticosteroids\n20. Use of any investigational drugs within 1 month, or five half-lives, whichever is longer, of the study procedures\n21. Presence of any current suicidality or a lifetime history of suicide attempt or suicidal ideation within the past year\n22. History of serious mental illnesses including psychotic disorders, bipolar disorders, severe anxiety, mood, or trauma-related disorders and other psychiatric conditions which in the opinion of the investigators would impede the patient's participation or compliance in the study\n23. History of liver decompensation events such as hepatic encephalopathy or ascites\n24. History of severe gastroparesis\n25. History of pancreatitis in the last 5 years or if subject has chronic pancreatitis\n\nFor optional MRI: a) Presence of ferromagnetic objects in the body that may be adversely affected by or contraindicated for MRI, fear of enclosed spaces, or other standard contraindication to MRI, as determined by self-report b) Use of MRI- incompatible intrauterine device (IUD).\n\nIndividuals who are pregnant or breastfeeding, or with severe hepatic or renal liver impairment will be excluded from this study because there is no clinical data on the safety of tirzepatide in these populations, including the impact on the fetus or infant. To assess pregnancy status, participants who can become pregnant will be required to take a urine pregnancy test and to test negative before administering study drug.","minimumAge":"21 Years","maximumAge":"100 Years","sex":"ALL","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks."},{"type":"OTHER","name":"Placebo","description":"A 2.5mg, 5mg, and 7.5mg subcutaneous injection will be given once weekly for 12 weeks."}],"primaryOutcomes":[{"measure":"Metabolic improvement from baseline as measured by percentage reduction of body weight and reduction in liver steatosis from baseline as measured by percentage reduction in Fibroscan controlled attenuation parameter (CAP) score.","description":null,"timeFrame":"Change from baseline to week 12"}],"secondaryOutcomes":[{"measure":"Reduction from baseline in - 1) Liver steatosis as measured by MRI spectroscopy, 2) MRI visceral fat, 3) Liver enzymes (ALT, AST, GGT), 4) Drinking behaviors/cravings, 5) WHO risk drinking level","description":null,"timeFrame":"Change from baseline to week 12"}],"publications":[{"pmid":"30473097","citation":"Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3."}],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07046819"},{"nctId":"NCT07214948","title":"Open, Randomized Feasibility Trial on the Safety and Performance of the INGA Catheter for Labor Induction","officialTitle":"An Open, Parallel-group, Randomized, Early Feasibility Trial to Evaluate the Initial Safety and Performance of the INGA Catheter in Labor Induction","summary":"This study investigates the safety and usability of the new INGA catheter for labor induction.\n\nLabor induction is common, with about one in three births being induced. In this study, the INGA catheter will be compared to a currently used method. The INGA catheter is a single-balloon device that works similarly to a Foley catheter but is made from different materials. Feedback will be collected from both healthcare professionals and participating women.","detailedDescription":"Screening Phase\n\nBefore any study-related procedures are initiated, participants will be asked to read and sign the informed consent form. Once consent is obtained, the following screening assessments will be performed to determine eligibility for participation:\n\n* Confirmation of informed consent.\n* Review of inclusion and exclusion criteria to ensure suitability for the study.\n* Collection of medical and demographic information, including medical history, concurrent or previous medications, planned delivery date, gestational age, and indication for labor induction.\n* Cervical assessment by palpation.\n* Measurement of blood pressure and heart rate.\n* Cardiotocography (CTG) monitoring of fetal heart rate and uterine contractions for a minimum of 30 minutes.\n* Ultrasound examination within one week prior to induction, to evaluate fetal weight, well-being, and overall status.\n\nIf the screening assessments confirm that the participant meets all eligibility criteria, she will proceed to the study phase and receive the assigned study device.\n\nStudy Device and Randomization\n\nAfter signing the informed consent form, each eligible participant will be randomly assigned to one of two treatment groups:\n\n* 1 in 2 chance of receiving the commonly used balloon catheter for labor induction.\n* 1 in 2 chance of receiving the INGA catheter, the investigational device being studied.\n\nThis is an open-label study, meaning that both the participant and the study personnel (including the investigator and sponsor) will know which device is used.\n\nThe study procedure follows the standard clinical process for balloon catheter-based induction of labor. No additional or experimental procedures are performed beyond the use of the assigned catheter. The only difference from routine clinical practice is the use of the INGA catheter in the investigational group.\n\nStudy Procedures\n\nParticipants will undergo the following procedures as part of the study:\n\n* The catheter (either the standard or INGA catheter) will be inserted by a trained physician through the vagina and advanced through the cervical canal.\n* The balloon portion of the catheter will be inflated with sterile saline to secure its position and will be fastened to the inner thigh to maintain placement.\n* Fetal heart rate monitoring (CTG) will be performed both before and after catheter placement, following standard hospital protocol.\n* Cervical ripeness will be assessed prior to catheter insertion and again after catheter removal or spontaneous expulsion.\n* The catheter will remain in place until it detaches spontaneously or for a maximum duration of 24 hours.\n* After catheter removal, cervical status will be reassessed, and labor induction will continue according to the hospital's standard of care.\n\nThroughout the procedure, the principal investigator and hospital staff will closely monitor the induction process and ensure the safety and well-being of both the mother and the fetus.\n\nComprehensive data will be collected on:\n\n* The course of pregnancy and labor induction process.\n* Delivery outcomes, including type and duration of delivery.\n* Maternal safety data, including any adverse events or complications. Infant Assessments\n\nFollowing labor and delivery, the following evaluations will be conducted for the newborn:\n\n* Birth weight and length.\n* Apgar score at 5 minutes post-delivery.\n* Collection of clinical data related to any neonatal diagnoses, treatments, or medical conditions.\n\nQuestionnaires\n\nTo assess user experience and device tolerability, the following questionnaires will be completed:\n\n* Participants will be asked to complete a short questionnaire evaluating their overall comfort, well-being, and any discomfort or pain experienced during placement and use of the balloon catheter.\n* The physician performing the catheter placement will complete a usability questionnaire to assess the practicality, ease of use, and general handling of the device.\n\nPost-Treatment Phase\n\nAfter completion of the study procedure:\n\n* The study device (INGA catheter or standard catheter) will be used only during this research study and will not be available for use after study participation ends.\n* No additional study visits or treatments are required once labor induction and delivery are complete.\n* Routine post-delivery care will be provided according to standard hospital practices.\n\nParticipant Expectations\n\nBy agreeing to participate in this study, each participant is expected to:\n\n* Read, understand, and sign the informed consent document.\n* Meet all inclusion criteria and not meet any exclusion criteria.\n* Understand that randomization will determine which study device is used.\n* Allow collection of maternal and neonatal health data for study analysis.\n* Complete the participant questionnaire regarding her experience with the catheter.","peptideSlugs":["oxytocin"],"peptideNames":["Oxytocin"],"conditions":["Induction of Birth","Cervical Ripening","Cervical Ripening and Induction of Labor"],"keywords":["Induction of labor","Balloon Catheter","Cervical ripening"],"conditionGroups":[{"slug":"other","label":"Other"}],"sponsor":{"name":"Aalto University","slug":"aalto-university","class":"OTHER"},"collaborators":[{"name":"University of Mississippi Medical Center","slug":"university-of-mississippi-medical-center","class":"OTHER"},{"name":"University of Minnesota","slug":"university-of-minnesota","class":"OTHER"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["NA"],"slugs":["not-applicable"],"labels":["Not applicable"],"label":"Not applicable","highest":0},"studyType":"INTERVENTIONAL","enrollment":40,"dates":{"start":"2026-07-03","primaryCompletion":"2026-09-30","completion":"2026-10-30","firstPosted":"2025-10-09","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":2,"countries":["United States"],"locations":[{"facility":"University of Minnesota Medical School","status":"RECRUITING","city":"Minneapolis","state":"Minnesota","country":"United States","latitude":44.97997,"longitude":-93.26384},{"facility":"University of Mississippi Medical Center","status":"NOT_YET_RECRUITING","city":"Jackson","state":"Mississippi","country":"United States","latitude":32.29876,"longitude":-90.18481}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Pregnant women aged ≥18 and ≤56 years\n* An unripe cervix, ≤6 points according to the Bishop score assessment (0-10-point scale)\n* Planned induction of labor by balloon catheter method\n* Gestational age at the time of the study ≥ 37 weeks (gestational age confirmed by ultrasound before the 21st week of pregnancy)\n* Singleton pregnancy\n* Cephalic presentation\n* The subject understands the study information and signs the informed consent\n\nExclusion Criteria:\n\n* Preterm induction of labor (\\<37 weeks of gestation)\n* Abnormal Cardiotocography (CTG) at inclusion\n* Spontaneous rupture of membranes at inclusion\n* Clinically significant vaginal bleeding with a need of hospitalization in the third trimester\n* Clinical active vaginal or uterine infection\n* Maternal Human Immunodeficiency Virus (HIV), hepatitis C, or hepatitis B\n* Uterine scar (including previous cesarean section)\n* Condition requiring immediate delivery of the fetus or mother\n* Presence of eclampsia\n* Severe Preeclampsia \\[Blood pressure (BP)≥ 160/110 and any of the following: thrombocytopenia with platelet count \\<100 × 10e9/L, HELLP- syndrome ( Hemolysis, Elevated Liver enzymes and Low Platelets), progressive renal insufficiency, pulmonary edema \\]\n* Severe fetal growth restriction (Fetal Growth Restriction (FGR) fetal growth \\<-2 SD/\\<10th percentile)\n* Estimated fetal weight ≥ 2 Standard Deviation /≥ 95th percentile\n* Reduced amniotic fluid volume (deepest vertical pocket \\<30 mill meter)\n* Breech or transverse fetal position\n* Multiple pregnancy\n* Vasa previa or placenta previa\n* Umbilical cord prolapses\n* Bishop score ≥6 on cervical assessment prior to labor induction\n* Receiving epidural anesthesia prior to catheter insertion\n* Refusal to participate in the study and/or insufficient language skills to understand the study information and/or consent form","minimumAge":"18 Years","maximumAge":"56 Years","sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DEVICE","name":"INGA Catheter","description":"Insertion of the INGA balloon catheter (medical device) through the cervical canal into the uterus is performed for labor induction. During a vaginal examination, the Investigator inserts the catheter so that the balloon tip lies between the amniotic membranes and the internal cervical os. The balloon is filled with 50-75 ml of sterile saline (NaCl) and secured to the upper thigh to maintain gentle traction. The catheter remains in place for up to 24 hours or until spontaneous expulsion. If not expelled, it is removed after 24 hours.\n\nAfter expulsion or removal, cervical status and Bishop score are assessed. If Bishop ≥ 6, amniotomy and/or oxytocin induction are initiated within one hour. If Bishop \\< 6, further management follows"},{"type":"DEVICE","name":"Currently used single balloon catheter","description":"Insertion of a balloon catheter through the cervical canal into the uterus for induction of labor."}],"primaryOutcomes":[{"measure":"Bishop Score Change","description":"Change in Bishop score (A scale from 1 to 10) during cervical ripening, with scores assessed before catheter insertion and after catheter detachment.","timeFrame":"From catheter insertion to detachment"}],"secondaryOutcomes":[{"measure":"Placement success","description":"Whether the catheter is placed successfully","timeFrame":"At catheter insertion"},{"measure":"Retention time of balloon catheter","description":"The time the balloon catheter remains in the cervix for cervical ripening","timeFrame":"From catheter placement to detachment, 0-24 hours"},{"measure":"Induction to delivery interval","description":"Time from initiation of labor induction (balloon catheter insertion) to the delivery of the neonate. This includes both the cervical ripening phase and active labor. The outcome will capture the total duration of the induction-to-delivery process.","timeFrame":"rom the start of balloon catheter insertion until the birth of the neonate, 0-48 hours"},{"measure":"Mode of delivery","description":"The type of delivery for the participant, categorized as vaginal, vaginal operative or cesarean delivery","timeFrame":"From enrolment to birth"},{"measure":"Pain experience during catheter insertion and in-place time","description":"The participants will complete a structured questionnaire to assess any potential pain experienced during catheter placement and retention","timeFrame":"Within 60 minutes from catheter insertion"},{"measure":"Professional's experience of catheter insertion and usability","description":"The Investigators will complete a structured questionnaire to evaluate the ease of catheter placement, usability, quality, appearance, and balloon inflation. The questionnaire also includes questions regarding their willingness to use technological applications in the context of labor induction.","timeFrame":"From catheter insertion to detachment"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07214948"},{"nctId":"NCT07257484","title":"Tirzepatide's Role in Postmenopausal HR+ Breast Cancer Survivors","officialTitle":"Tirzepatide's Role in Postmenopausal HR+ Breast Cancer Survivors","summary":"This study will explore whether tirzepatide is a practical and acceptable treatment for postmenopausal females with a history of hormone receptor-positive breast cancer and obesity. The investigators aim to understand whether participants are willing and able to take this medication once weekly for 6 months and whether it may help improve weight and overall health. There will be monthly check-ins to monitor progress and safety. At the beginning and end of the study, participants will undergo body composition assessments, blood tests and a stool sample will be collected, and surveys will be completed.","detailedDescription":null,"peptideSlugs":["tirzepatide","glucagon"],"peptideNames":["Tirzepatide","Glucagon"],"conditions":["Obesity (Disorder)","Breast Cancer"],"keywords":["tirzepatide","hormone receptor positive","HR+","postmenopausal"],"conditionGroups":[{"slug":"weight-loss","label":"Weight loss"}],"sponsor":{"name":"Weill Medical College of Cornell University","slug":"weill-medical-college-of-cornell-university","class":"OTHER"},"collaborators":[{"name":"National Center for Advancing Translational Sciences (NCATS)","slug":"national-center-for-advancing-translational-sciences-ncats","class":"NIH"}],"status":{"raw":"RECRUITING","group":"recruiting","label":"Recruiting"},"phases":{"raw":["PHASE4"],"slugs":["phase-4"],"labels":["Phase 4"],"label":"Phase 4","highest":4},"studyType":"INTERVENTIONAL","enrollment":30,"dates":{"start":"2026-06-08","primaryCompletion":"2027-12-03","completion":"2028-02-25","firstPosted":"2025-12-02","resultsPosted":null,"lastUpdated":"2026-07-22"},"hasResults":false,"locationCount":1,"countries":["United States"],"locations":[{"facility":"Weill Cornell Medicine","status":"RECRUITING","city":"New York","state":"New York","country":"United States","latitude":40.71427,"longitude":-74.00597}],"eligibility":{"criteria":"Inclusion Criteria:\n\n* Biologically female\n* Age ≥ 18\n* Obesity as defined by current BMI ≥ 30 kg/m² or ≥ 27.5 kg/m² for individuals of Asian ancestry\n* Postmenopausal as defined by one or more of the following\n\n  * Age ≥60 years\n  * Age \\<60 years with amenorrhea for ≥ 1 year\n  * Documented bilateral surgical oophorectomy\n  * Chemical menopause with the addition of LHRH agonists at least 12 weeks prior to enrolment, and plan to remain on LHRH agonists throughout the trial\n* HR+ (ER and/or PR) stage 0-III breast cancer\n* Completed curative treatment (surgery, chemotherapy, radiotherapy) at least 12 weeks prior to enrolment\n* Insurance approval for tirzepatide or willing to pay out of pocket\n* Willing to provide informed consent and comply with study procedures\n\nExclusion Criteria:\n\n* Stage IV breast cancer\n* Concomitant use of CDK inhibitors\n* Concomitant use of antiHER2 therapy\n* The PI may be consulted regarding enrollment of females receiving other endocrine therapy medications\n* Other active malignancy requiring treatment\n* Enrollment in another investigational clinical trial\n* Contraindication to tirzepatide\n* Treatment with a GLP-1 receptor agonist within the last 3 months\n* Diabetes requiring insulin\n* Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol","minimumAge":"18 Years","maximumAge":null,"sex":"FEMALE","healthyVolunteers":false},"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Participants will take tirzepatide weekly for 24 weeks. The dose will be adjusted on a monthly basis as clinically indicated."}],"primaryOutcomes":[{"measure":"Percentage of participants completing week 24 visit with all required assessments","description":null,"timeFrame":"24 weeks"}],"secondaryOutcomes":[{"measure":"Percent change in body weight from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Absolute change in visceral fat mass from baseline to week 24","description":"As assessed by SECA scan","timeFrame":"Baseline, 24 weeks"},{"measure":"Percent change in visceral fat mass from baseline to week 24","description":"As assessed by SECA scan","timeFrame":"Baseline, 24 weeks"},{"measure":"Absolute change in fasting glucose from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Percent change in fasting glucose from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Absolute change in fasting insulin from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Percent change in fasting insulin from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Absolute change in hemoglobin A1c from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Percent change in hemoglobin A1c from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"},{"measure":"Absolute change in IGF-1 from baseline to week 24","description":null,"timeFrame":"Baseline, 24 weeks"}],"publications":[],"sourceRegistry":"ClinicalTrials.gov","sourceUrl":"https://clinicaltrials.gov/study/NCT07257484"}]}