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CompletedNCT02621489RebuildUpdated Apr 20, 2023

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

A Phase 4 interventional study of Bydureon and Humulin kwickpen in Atherosclerosis, Diabetes and Restenosis, sponsored by Karolinska Institutet. Completed at 1 site in Sweden. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-04-20.

Sponsored by Karolinska Institutet · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
38
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

  • Atherosclerosis
  • Diabetes
  • Restenosis

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Keywords

  • Glucagon-like peptide-1
  • Endothelialization
  • Cardiac Function
  • Exenatide
  • Optical Coherence Tomography
03

In context

Atherosclerosis

1,567 studies on the registry are indexed under Atherosclerosis; 264 are open to participants now.

This study's enrollment of 38 is below the median of 106 across 882 interventional studies indexed under Atherosclerosis.

Browse Atherosclerosis studies →

Lead sponsor

Karolinska Institutet is the lead sponsor of 1,113 studies on the registry; 267 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
38 participants (actual)

Study arms

  • Experimental
    Bydureon 2 mg Once Weekly

    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: Bydureon · Drug: Humulin kwickpen · Drug: Metformin

  • Active comparator
    Humulin kwickpen

    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 kwickpen · Drug: Metformin

Interventions

  • DrugBydureon

    2 mg Once Weekly

    Also known as: Exenatide

  • DrugHumulin kwickpen

    Humulin kwickpen 10U QD at bedtime

    Also known as: Insulin Aspart

  • DrugMetformin

    Metformin 1g BID

    Also known as: Biguanide

06

What researchers measure

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).

    Time frame: 12 weeks

Secondary outcomes

  1. Fractional Flow Reserve (FFR)

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

    Time frame: 12 weeks

  2. Coronary Flow velocity Reserve (CRF)

    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.

    Time frame: 12 weeks

  3. Index of Microcirculatory Resistance (IMR)

    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

    Time frame: 12 weeks

  4. Fractional flow reserve positive re-stenosis

    Time frame: 12 weeks

  5. Target lesion failure

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

    Time frame: 12 weeks

  6. Acute coronary syndrome (ACS) and/or repeat revascularization

    Time frame: 12 weeks

  7. Late lumen loss/neointima thickness measured with OCT

    Time frame: 12 weeks

  8. Change in minimal lumen area by OCT

    Time frame: 12 weeks

  9. Left ventricular systolic and diastolic function assessed by echocardiography

    Time frame: 12 weeks

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

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

    Time frame: 12 weeks

  11. Plasma markers of endothelial activation i.e., E-Selectin, VCAM-1, ICAM-1, nitrotyrosine levels

    Time frame: 12 weeks

  12. Plasma markers of inflammation i.e., CRP, IL-1β, IL-6 and IL-8.

    Time frame: 12 weeks

  13. Plasma markers of matrix remodeling enzymes i.e., MMP-2 and MMP9

    Time frame: 12 weeks

  14. Circulating endothelial progenitor cells

    Time frame: 12 weeks

  15. Gene expression (Affymetrix) e.g., transcription factors of sirtuins (SIRT) and nitric oxide synthase (NOS)

    Time frame: 12 weeks

07

Study locations

1 site
  • Dept of clinical science and education Karolinska Institutet Södersjukhuset
    Stockholm, Other 11883, Sweden
08

References and documents

Publications

  • 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. PubMed 25966620 ↗
  • 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. PubMed 23343509 ↗
  • 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. PubMed 20452396 ↗
  • 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. PubMed 22390929 ↗
  • 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. PubMed 15353407 ↗
  • 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. Erratum In: Am J Physiol Heart Circ Physiol. 2018 Dec 1;315(6):H1861. doi: 10.1152/ajpheart.zh4-0651-corr.2018. PubMed 23241323 ↗
  • 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. PubMed 20630463 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 20, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02621489
Lead sponsor
Karolinska Institutet
Responsible party
Thomas Nystrom (MD, PhD, Karolinska Institutet) — Principal investigator
First posted
Dec 3, 2015
Start date
Dec 2015
Primary completion
Aug 2022
Completion
Oct 2022
Last update
Apr 20, 2023

Study contacts

Thomas Nyström
principal investigator · Karolinska Institutet

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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