NCT01595789已完成4 期
Adding Liraglutide to the Backbone Therapy of Biguanide in Patients With Coronary Artery Disease and Newly Diagnosed Type-2 Diabetes
Haugaard, Steen Bendix, M.D., DMSc1 个研究点 分布在 1 个国家目标入组 41 人开始时间: 2012年5月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- LVEF
研究概览
简要总结
The purpose of this study is to investigate the effect of combined glucagon-like-peptide-1 (GLP-1) analogue and metformin therapy on glucose metabolic and cardiovascular endpoints compared to metformin monotherapy in patients with coronary artery disease (CAD) and newly diagnosed type 2 diabetes (T2D).
It is hypothesized that GLP-1 analogue added to backbone therapy of metformin in CAD patients with T2D will improve beta-cell function, left ventricular ejection fraction (LVEF), heart rate variability and lower 24h blood pressure among other selected endpoints.
The present study on CAD patients with newly diagnosed T2D will address these selected endpoints during an investigator initiated, randomized, double blind, crossover, placebo-controlled 12 + 12 weeks intervention study with a 2 week wash-out period.
详细描述
The total study period for each patient will be 26 weeks (12 plus 12 weeks of intervention with a 2 week wash-out period).
The endpoints will be evaluated at baseline (week 0), at week 12, at week 14 (following 2 weeks of wash-out) and finally at week 26.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stable CAD documented by one of the following:
- •Previous MI (a minimum of 6 weeks after an acute MI)
- •Previous coronary revascularization
- •CAD confirmed by an abnormal coronary angiography (CAG) or CT-angiography showing stenosis > 50% of any major coronary arteries.
- •Body mass index (BMI) >/= 25,0 kg/m2
- •Age >/= 18 years and </= 85 years
- •Type 2 diabetes diagnosed by one of the following criteria:
- •HbA1c >/= 6.5%
- •HbA1c < 6.5 % and fasting plasma glucose >/= 7.0 mmol/l (confirmed)
- •HbA1c < 6.5 % and a 2 h plasma glucose value during OGTT >/= 11.1 mmol/l
- •The data for glucose metabolism are accepted provided that they have been obtained within 24 months prior to inclusion of the patient. The glucose metabolic categories are defined by ADA and WHO criteria.
排除标准
- •Type 1 diabetes mellitus defined as C-peptide < 450 pM
- •Previously diagnosed diabetes mellitus for more than 24 months prior to the screening procedure for this trial, except from gestational diabetes
- •Use of more than 2 types of oral antidiabetic medication and/or use of parenteral antidiabetic medication in the period of 3 months prior to the screening visit. It is accepted that the patient continues his usual antidiabetic medication after the screening visit but antidiabetic medication must be discontinued 2 weeks prior to the baseline visit.
- •Significant heart disease (NYHA > 2; Ejection Fraction < 40% and unstable angina pectoris) and known severe valve disease
- •Documented atrial fibrillation or atrial flutter within 6 weeks previous to the screening. Paroxysmal atrial fibrillation is accepted if sinus rhythm is achieved at the screening.
- •Uncontrolled arterial hypertension (> 180/100 mmHg) at the time of screening
- •Liver (transaminases greater than x 2 the upper normal level) or renal diseases (eGFR < 60 ml/min)
- •Amylase greater than x 3 the upper reference value
- •Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators
- •Dysregulated myxedema or hyperthyroid condition defined by a value of TSH < 0,1 and > 10,0 milli U/L
- •Anemia (< 85% of lower normal limit), leucopenia (< 85% of lower normal limit), or thrombocytopenia (< 85% of lower normal limit)
- •Pregnancy or failure to comply with contraception planning within two years, or breastfeeding
- •Abuse of alcohol or drugs, or any other co-existing condition that would make patients unsuitable to participate in the study, as judged by the investigators
- •Use of immunosuppressive therapy in the preceding 12 months
- •Chronic pancreatitis or previous acute pancreatitis
- •Known or suspected hypersensitivity to trial product(s) or related products
- •Treatment with oral glucocorticoids, calcineurin inhibitors, or dipeptidyl peptidase 4 (DPP4) inhibitors, or other GLP-1 mimetics (e.g. exenatide), which in the Investigator's opinion could interfere with glucose metabolism
- •Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, which in the Investigator's opinion could interfere with the results of the trail
- •Inflammatory bowel disease
- •Previous bowel resection
- •Clinical signs of diabetic gastroparesis
- •Plasma calcium-ion >/= 1,45 mmol/L
- •Plasma calcitonin >/= 50 ng/L
- •Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2
- •Refusal to sign informed consent.
研究组 & 干预措施
Placebo + metformin
Placebo Comparator
干预措施: Placebo (Drug)
Liraglutide + metformin
Active Comparator
干预措施: Liraglutide (Drug)
结局指标
主要结局
LVEF
时间窗: after 12 weeks of intervention
Changes in LVEF assessed by dobutamine stress echocardiography
Beta-cell function
时间窗: after 12 weeks of intervention
Beta-cell function (disposition index) as measured during an intravenous glucose tolerance test (By Bergman Minimal Model)
次要结局
- ST-depression and ectopic activity(Baseline (week 0), week 12, week 14, week 26)
- Diurnal blood pressure(Baseline (week 0), week 12, week 14, week 26)
- Glucagon, incretin, glucose, NEFA, insulin and C-peptide response during meal test(Baseline (week 0), week 12, week 14, week 26)
- Non esterified fatty acids (NEFA)(Baseline (week 0), week 12, week 14, week 26)
- Heart rate variability (HRV)(Baseline (week 0), week 12, week 14, week 26)
- Diastolic heart function (E/E*)(Baseline (week 0), week 12, week 14, week 26)
- Maximal velocity of the myocardium in systole (s´) and in diastole (e´)(Baseline (week 0), week 12, week 14, week 26)
- Insulin sensitivity (Si), acute insulin and C-peptide response to intravenous glucose (AIRg, ACRg), glucose clearance (Kg), glucose effectiveness (Sg) and hepatic extraction of insulin (HEXi)(Baseline (week 0), week 12, week 14, week 26)
- CRP, TNF-alfa and IL-6 in plasma and gene expression of IL6 and TNF-alfa in subcutaneous fat(Baseline (week 0), week 12, week 14, week 26)
- Changes in exercise tolerance test variables: Total exercise duration (sec), time to limiting angina (sec) and time to 1 mm ST-segment depression (sec)(Baseline (week 0), week 12, week 14, week 26)
研究者
研究点 (1)
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