NCT02621489

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Dec 2015

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 22, 2015

Completed
9 days until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 3, 2015

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2022

Completed
Last Updated

April 20, 2023

Status Verified

April 1, 2023

Enrollment Period

6.7 years

First QC Date

November 22, 2015

Last Update Submit

April 19, 2023

Conditions

AtherosclerosisDiabetesRestenosis

Keywords

Glucagon-like peptide-1EndothelializationCardiac FunctionExenatideOptical Coherence Tomography

Outcome Measures

Primary Outcomes (1)

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

    12 weeks

Secondary Outcomes (15)

  • Fractional Flow Reserve (FFR)

    12 weeks

  • Coronary Flow velocity Reserve (CRF)

    12 weeks

  • Index of Microcirculatory Resistance (IMR)

    12 weeks

  • Fractional flow reserve positive re-stenosis

    12 weeks

  • Target lesion failure

    12 weeks

  • +10 more secondary outcomes

Study Arms (2)

Bydureon 2 mg Once Weekly

EXPERIMENTAL

Patients randomised to Bydureon will be treated with Metformin 1g BID, and only receive 10U of Humulin kwickpen QD at bedtime, with no more up-titration of insulin during the study.

Drug: BydureonDrug: Humulin kwickpenDrug: Metformin

Humulin kwickpen

ACTIVE COMPARATOR

Patients randomised to the comparator group will be treated with Meformin 1g BID and Humulin kwickpen to reach a fP-glucose level of 6 mmol/l. For that reason patients will be instructed to increase the bedtime Insulin dose of 2-4U every third day until this goal is reached.

Drug: Humulin kwickpenDrug: Metformin

Interventions

BydureonDRUG

2 mg Once Weekly

Also known as: Exenatide
Bydureon 2 mg Once Weekly
Humulin kwickpenDRUG

Humulin kwickpen 10U QD at bedtime

Also known as: Insulin Aspart
Bydureon 2 mg Once WeeklyHumulin kwickpen
MetforminDRUG

Metformin 1g BID

Also known as: Biguanide
Bydureon 2 mg Once WeeklyHumulin kwickpen

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients eligible for PCI with application of DES, due to ACS.
  • 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)
  • Male and female subjects 18-80 years.
  • HbA1c (accordingly to IFCC) 47 mmol/mol - 110 mmol/mol.
  • Signed informed consent form.

You may not qualify if:

  • Type 1 diabetes (autoantibody positive).
  • Any history of receiving GLP-1 analogues or dipeptidyl peptidase inhibitors within 6 months
  • Known severe heart failure, classified as NYHA 4.
  • Active myocarditis; malfunctioning artificial heart valve.
  • History of ventricular tachycardia within 3 months before study entry; second- or third-degree atrioventricular block.
  • Supine systolic blood pressure \<85 mm Hg or \>200 mm Hg at screening.
  • Primary renal impairment, creatinine clearance \< 45 ml/min if treated with metformin.
  • Uncorrected hypokalemia or hyperkalemia (potassium \<3.5 mmol/l or \>5.5 mmol/l).
  • Significant anemia (Hb \< 90 g/l)
  • Severe gastrointestinal disease, including gastroparesis. As judged by the Investigator.
  • Body mass index (BMI) \> 45 kg/m2.
  • 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.
  • Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant.
  • Current drug and alcohol abuse.
  • History of acute or chronic pancreatitis
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dept of clinical science and education Karolinska Institutet Södersjukhuset

Stockholm, Other, 11883, Sweden

Location

Related Publications (8)

  • Eriksson 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: 25966620RESULT

  • Erdogdu 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: 23343509RESULT

  • Erdogdu 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: 20452396RESULT

  • Erdogdu 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: 22390929RESULT

  • Nystrom 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: 15353407RESULT

  • Dokken 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: 23241323RESULT

  • Guagliumi 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: 20630463RESULT

  • Santos-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.

    PMID: 38066597DERIVED

MeSH Terms

Conditions

AtherosclerosisDiabetes Mellitus

Interventions

ExenatideInsulin AspartMetforminBiguanides

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological FactorsInsulin, Short-ActingInsulinsPancreatic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Thomas Nyström

    Karolinska Institutet

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

November 22, 2015

First Posted

December 3, 2015

Study Start

December 1, 2015

Primary Completion

August 1, 2022

Study Completion

October 1, 2022

Last Updated

April 20, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will not share

Locations

SE(1)