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

Phase 4

Completed

• Conditions: Restenosis; Diabetes; Atherosclerosis
• Interventions: Drug: Bydureon; Drug: Humulin kwickpen; Drug: Metformin

• Registration Number: NCT02621489
• Lead Sponsor: Karolinska Institutet

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.

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-11-22
• Study Start: 2015-12
• Study First Submitted QC: 2015-12-01
• Study First Posted: 2015-12-03
• Primary Completion: 2022-08
• Study Completion: 2022-10
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-19
• Last Update Posted: 2023-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bydureon 2 mg Once Weekly	Humulin kwickpen	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.
Bydureon 2 mg Once Weekly	Bydureon	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.
Humulin kwickpen	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.
Bydureon 2 mg Once Weekly	Metformin	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.
Humulin kwickpen	Metformin	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Late lumen loss/neointima thickness measured with OCT	12 weeks
Recovery from endothelial damage, measured by high resolution ultrasound, after PCI	12 weeks	Non-invasive ultrasound over the radialis artery after the PCI procedure using Standard 6-7F guiding catheters.
Plasma markers of inflammation i.e., CRP, IL-1β, IL-6 and IL-8.	12 weeks
Coronary Flow velocity Reserve (CRF)	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)	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	12 weeks
Plasma markers of matrix remodeling enzymes i.e., MMP-2 and MMP9	12 weeks
Gene expression (Affymetrix) e.g., transcription factors of sirtuins (SIRT) and nitric oxide synthase (NOS)	12 weeks
Fractional Flow Reserve (FFR)	12 weeks	FFR is a unitless index calculated as the ratio between distal coronary and aortic pressure during maximum hyperemia.
Circulating endothelial progenitor cells	12 weeks
Target lesion failure	12 weeks	Need of unplanned PCI in the treated stenosis or significant re-stenosis in the follow-up
Change in minimal lumen area by OCT	12 weeks
Left ventricular systolic and diastolic function assessed by echocardiography	12 weeks
Acute coronary syndrome (ACS) and/or repeat revascularization	12 weeks
Plasma markers of endothelial activation i.e., E-Selectin, VCAM-1, ICAM-1, nitrotyrosine levels	12 weeks

Trial Locations

Locations (1)

Dept of clinical science and education Karolinska Institutet Södersjukhuset; 🇸🇪 Stockholm, Other, Sweden