Effects on Re-endothelialisation With Bydureon Treatment Add on to Insulin Versus Insulin Alone, Both in Combination With Metformin in Type 2 Diabetic Subjects
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- The degree of non-covered stent struts by Bydureon add on to Insulin over that of Insulin as analyzed by optical coherence tomography (OCT).
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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/m
- •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
- •Subjects considered by the Investigator to be unsuitable for the study.
研究组 & 干预措施
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.
干预措施: Bydureon (Drug)
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.
干预措施: Humulin kwickpen (Drug)
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.
干预措施: Metformin (Drug)
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.
干预措施: Humulin kwickpen (Drug)
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.
干预措施: Metformin (Drug)
结局指标
主要结局
The degree of non-covered stent struts by Bydureon add on to Insulin over that of Insulin as analyzed by optical coherence tomography (OCT).
时间窗: 12 weeks
次要结局
- Plasma markers of inflammation i.e., CRP, IL-1β, IL-6 and IL-8.(12 weeks)
- Circulating endothelial progenitor cells(12 weeks)
- Target lesion failure(12 weeks)
- 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)
- Coronary Flow velocity Reserve (CRF)(12 weeks)
- Index of Microcirculatory Resistance (IMR)(12 weeks)
- 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)
- Late lumen loss/neointima thickness measured with OCT(12 weeks)
- Recovery from endothelial damage, measured by high resolution ultrasound, after PCI(12 weeks)
研究者
Thomas Nystrom
MD, PhD
Karolinska Institutet