PROCEDURE
Biopsy
Undergo biopsy
Status
Completed
Phase
Phase 1
Enrollment
43
Locations
4
Results
Not posted
Publications
0
Study summary
This early phase I trial studies the guanylyl cyclase C (GCC) agonist effect on cGMP signal in duodenal tissue. Plecanatide and linaclotide are drugs approved by the Food and Drug Administration for the treatment of conditions related to constipation. This trial aims to see the effects of taking either one of two drugs, plecanatide or linaclotide, or no drug, on a certain chemical found in the tissue collected from small intestine and how they compare.
PRIMARY OBJECTIVE: I. To assess and compare participants randomly assigned 1:1:1 to one of three intervention arms (plecanatide 3 mg versus linaclotide 145 mcg versus no active agent) with respect to change in cyclic guanosine monophosphate (cGMP) accumulation in normal appearing duodenal mucosa specimens. SECONDARY OBJECTIVES: I. Characterization and comparison of the following outcomes (in prioritized order): Ia. cGMP levels in luminal fluid from participants receiving either linaclotide or plecanatide to fluid from participants receiving no agent; Ib. Vasodilator stimulated phosphoprotein (VASP) phosphorylation in normal-appearing duodenal mucosa biopsy specimens from participants receiving either linaclotide or plecanatide to those specimens from participants receiving no agent. EXPLORATORY OBJECTIVES: I. Comparison of cGMP and VASP phosphorylation between the plecanatide and linaclotide arms. II. Transcriptome analysis of cellular response (ribonucleic acid \[RNA\] sequencing analyses) to define whether GCC ligand exposure induces reproducible changes in duodenal messenger \[m\]RNA expression that can serve as a reliable biomarker of GCC-cGMP signaling in future studies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive a single dose of plecanatide (3 mg) orally (PO) 60-120 minutes prior to standard of care esophagogastroduodenoscopy (EGD) with biopsy and luminal fluid collection. Patients also undergo biopsy on study. ARM II: Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study. ARM III: Patients undergo standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study. After completion of study intervention, patients are followed up at day 7.
Interventions
PROCEDURE
Undergo biopsy
PROCEDURE
Undergo collection of luminal fluid
PROCEDURE
Undergo EGD
DRUG
Given PO
DRUG
Given PO
Timeline
First posted
Nov 4, 2021
Study start
Nov 30, 2022
Primary completion
Feb 6, 2026
Study completion
Feb 6, 2026
Results posted
Not reported
Registry updated
Apr 7, 2026
Outcomes
Cyclic guanosine monophosphate (cGMP) levels
Time frame · Up to 2 years
Will compare cGMP levels measured in normal-appearing duodenal mucosa biopsy specimens from participants receiving linaclotide or plecanatide to cGMP levels in specimens from participants receiving no active treatment. Will evaluate the difference between the control and each treated arm in cGMP levels using two-tailed two-sample Student t-tests. If necessary, a log transformation or Wilcoxon rank-sum will be used, as appropriate.
cGMP levels in luminal fluid
Time frame · Up to 2 years
Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa
Time frame · Up to 2 years
Eligibility
Inclusion Criteria: * Scheduled for clinically indicated esophagogastroduodenoscopy (EGD) * Age \>= 18 years of age. Note: Because no dosing or adverse event (AE) data are currently available on the use of plecanatide or linaclotide in participants \< 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable * Willing to provide mandatory biospecimens as specified in the protocol * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Not pregnant or breastfeeding, as determined by pregnancy test prior to EGD procedure. Note: The effects of plecanatide and linaclotide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, 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 2 weeks after discontinuing study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Breastfeeding should be discontinued if the mother is treated with plecanatide or linaclotide * Ability to understand and the willingness to sign a written informed consent document * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * 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 * Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible Exclusion Criteria: * Prior treatment in the past week with plecanatide, linaclotide, or other agent whose primary mechanism of action is that of a GCC agonist * History of allergic reactions attributed to compounds of similar chemical or biologic composition of plecanatide or linaclotide * Use of any other investigational agents =\< 12 weeks prior to registration * Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements * History of gastric bypass, gastric sleeve, or bariatric surgery
Study locations
United States. Showing up to 24 locations stored in the fast local snapshot.
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Publications
No PMID-linked publications were present in this registry snapshot.
Related trials
Mayo Clinic · Irritable Bowel Syndrome With Constipation
Not applicable
Recruiting
65
2026-07
Bausch Health Americas, Inc. · Functional Constipation (FC)
Phase 2
Active, not recruiting
180
2026-07
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Colorectal Adenoma · Stage 0 Colorectal Cancer AJCC v8
Phase 2
Active, not recruiting
150
2026-07
AbbVie · Functional Constipation (FC) · Chronic Idiopathic Constipation (CIC)
Phase 3
Completed
123
2026-05
University of Nottingham · Cystic Fibrosis (CF)
Early Phase 1
Recruiting
26
2026-05
Texas Tech University Health Sciences Center, El Paso · Chronic Constipation · Diabete Mellitus
Phase 4
Active, not recruiting
23
2026-04
Md Mehedi Shahriar · Chronic Idiopathic Constipation · Irritable Bowel Syndrome (IBS-C)
Phase 4
Not yet recruiting
90
2026-02
University of Florida · Patients Scheduled for Colonoscopy
Phase 1 / Phase 2
Recruiting
10
2026-01
Related PeptideStat pages
Research pages describe evidence. Vendor pages, where available, describe independently tracked research-product listings and are not clinical recommendations.