Current partner codePEPTIDESDE
NCT02621489·Phase 4·INTERVENTIONAL

Effects on Re-endothelialisation With Bydureon Treatment in Type 2 Diabetes Subjects

Status

Completed

Phase

Phase 4

Enrollment

38

Locations

1

Results

Not posted

Publications

8

Study summary

What the protocol is testing.

The aim of the study is to use Exenatide long-acting release (LAR) \[Bydureon\] to minimize vascular remodeling and neointima formation after Percutaneous Coronary Intervention (PCI) and to accelerate stent endothelialisation.

Full detailed description

Exenatide LAR will be given as a once-weekly (s.c.) dose of Bydureon (2 mg) add on to Insulin in combination with Metformin. If patients are Insulin naïve (both groups) an initial dose of 10U (s.c.) at bedtime will be started, and further up-titrated to achieve a fP-glucose levels at 6 mmol/l. Standard care for post myocardial infarction will be given after PCI. Primary objectives: To test whether Bydureon, add on to Insulin Neutral Protamine Hagedorn (NPH) + Metformin, is superior vs. Insulin NPH + Metformin alone, in covered stent struts Secondary objectives: To test whether Bydureon, add on to Insulin NPH + Metformin, is superior vs. Insulin NPH + Metformin alone: in cardiac and endothelial functions

Interventions

Treatment arms and agents.

DRUG

Bydureon

2 mg Once Weekly

DRUG

Humulin kwickpen

Humulin kwickpen 10U QD at bedtime

DRUG

Metformin

Metformin 1g BID

Timeline

From registration to results.

  1. First posted

    Dec 3, 2015

  2. Study start

    Dec 2015

  3. Primary completion

    Aug 2022

  4. Study completion

    Oct 2022

  5. Results posted

    Not reported

  6. Registry updated

    Apr 20, 2023

Outcomes

What the study measures.

Primary outcomes

The degree of non-covered stent struts by Bydureon add on to Insulin over that of Insulin as analyzed by optical coherence tomography (OCT).

Time frame · 12 weeks

Secondary outcomes

Fractional Flow Reserve (FFR)

Time frame · 12 weeks

FFR is a unitless index calculated as the ratio between distal coronary and aortic pressure during maximum hyperemia.

Coronary Flow velocity Reserve (CRF)

Time frame · 12 weeks

CFR is a unitless index calculated as the ratio between the the mean transit time recorded at maximum hyperemia and at baseline using the thermodilution.

Index of Microcirculatory Resistance (IMR)

Time frame · 12 weeks

IMR is a unitless index calculated by dividing the mean distal coronary pressure by the inverse of the mean transit time recorded using the thermodilution technique during maximum hyperemia

Fractional flow reserve positive re-stenosis

Time frame · 12 weeks

Target lesion failure

Time frame · 12 weeks

Need of unplanned PCI in the treated stenosis or significant re-stenosis in the follow-up

Acute coronary syndrome (ACS) and/or repeat revascularization

Time frame · 12 weeks

Late lumen loss/neointima thickness measured with OCT

Time frame · 12 weeks

Change in minimal lumen area by OCT

Time frame · 12 weeks

Left ventricular systolic and diastolic function assessed by echocardiography

Time frame · 12 weeks

Recovery from endothelial damage, measured by high resolution ultrasound, after PCI

Time frame · 12 weeks

Non-invasive ultrasound over the radialis artery after the PCI procedure using Standard 6-7F guiding catheters.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
80 Years
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: 1. Patients eligible for PCI with application of DES, due to ACS. 2. Patients with known or newly diagnosed T2D (type 2 diabetes is diagnosed according to current WHO criteria or by the use of anti-diabetic drugs) 3. Male and female subjects 18-80 years. 4. HbA1c (accordingly to IFCC) 47 mmol/mol - 110 mmol/mol. 5. Signed informed consent form. Exclusion Criteria: 1. Type 1 diabetes (autoantibody positive). 2. Any history of receiving GLP-1 analogues or dipeptidyl peptidase inhibitors within 6 months 3. Known severe heart failure, classified as NYHA 4. 4. Active myocarditis; malfunctioning artificial heart valve. 5. History of ventricular tachycardia within 3 months before study entry; second- or third-degree atrioventricular block. 6. Supine systolic blood pressure \<85 mm Hg or \>200 mm Hg at screening. 7. Primary renal impairment, creatinine clearance \< 45 ml/min if treated with metformin. 8. Uncorrected hypokalemia or hyperkalemia (potassium \<3.5 mmol/l or \>5.5 mmol/l). 9. Significant anemia (Hb \< 90 g/l) 10. Severe gastrointestinal disease, including gastroparesis. As judged by the Investigator. 11. Body mass index (BMI) \> 45 kg/m2. 12. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. Patients with intraepithelial squamous cell carcinoma of the skin treated with topical 5FU and subjects with basal cell skin cancer are allowed to enter the trial. 13. Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant. 14. Current drug and alcohol abuse. 15. History of acute or chronic pancreatitis 16. Subjects considered by the Investigator to be unsuitable for the study.

Study locations

1 registered sites.

Sweden. Showing up to 24 locations stored in the fast local snapshot.

Dept of clinical science and education Karolinska Institutet Södersjukhuset

Stockholm, Other, Sweden

Publications

Results and literature.

PMID 25966620Eriksson L, Saxelin R, Rohl S, Roy J, Caidahl K, Nystrom T, Hedin U, Razuvaev A. Glucagon-Like Peptide-1 Receptor Activation Does not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury. J Vasc Res. 2015;52(1):41-52. doi: 10.1159/000381097. Epub 2015 May 7.PMID 23343509Erdogdu O, Eriksson L, Xu H, Sjoholm A, Zhang Q, Nystrom T. Exendin-4 protects endothelial cells from lipoapoptosis by PKA, PI3K, eNOS, p38 MAPK, and JNK pathways. J Mol Endocrinol. 2013 Mar 18;50(2):229-41. doi: 10.1530/JME-12-0166. Print 2013 Apr.PMID 20452396Erdogdu O, Nathanson D, Sjoholm A, Nystrom T, Zhang Q. Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor. Mol Cell Endocrinol. 2010 Aug 30;325(1-2):26-35. doi: 10.1016/j.mce.2010.04.022. Epub 2010 May 7.PMID 22390929Erdogdu O, Eriksson L, Nystrom T, Sjoholm A, Zhang Q. Exendin-4 restores glucolipotoxicity-induced gene expression in human coronary artery endothelial cells. Biochem Biophys Res Commun. 2012 Mar 23;419(4):790-5. doi: 10.1016/j.bbrc.2012.02.106. Epub 2012 Feb 27.PMID 15353407Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, Sjoholm A. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1209-15. doi: 10.1152/ajpendo.00237.2004. Epub 2004 Sep 7.PMID 23241323Dokken BB, Piermarini CV, Teachey MK, Gura MT, Dameff CJ, Heller BD, Krate J, Ashgar AM, Querin L, Mitchell JL, Hilwig RW, Kern KB. Glucagon-like peptide-1 preserves coronary microvascular endothelial function after cardiac arrest and resuscitation: potential antioxidant effects. Am J Physiol Heart Circ Physiol. 2013 Feb 15;304(4):H538-46. doi: 10.1152/ajpheart.00282.2012. Epub 2012 Dec 15.PMID 20630463Guagliumi G, Sirbu V, Bezerra H, Biondi-Zoccai G, Fiocca L, Musumeci G, Matiashvili A, Lortkipanidze N, Tahara S, Valsecchi O, Costa M. Strut coverage and vessel wall response to zotarolimus-eluting and bare-metal stents implanted in patients with ST-segment elevation myocardial infarction: the OCTAMI (Optical Coherence Tomography in Acute Myocardial Infarction) Study. JACC Cardiovasc Interv. 2010 Jun;3(6):680-7. doi: 10.1016/j.jcin.2010.04.005.PMID 38066597Santos-Pardo I, Witt N, Angeras O, Nystrom T. Effects of exenatide on coronary stent's endothelialization in subjects with type 2 diabetes: a randomized controlled trial. The Rebuild study. Cardiovasc Diabetol. 2023 Dec 8;22(1):337. doi: 10.1186/s12933-023-02071-4.

Primary links

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