Can Metformin Prevent Endothelial Ischemia and Reperfusion Injury? The Metformin-FMD Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.
研究概览
简要总结
In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Ischemia and reperfusion (IR)-induced endothelial dysfunction seems to play a pivotal role in this process, resulting in vasoconstriction and reduced blood flow to the already ischemic tissue. Recently, it has been shown that the glucose-lowering drug metformin is able to limit IR-injury in murine models of myocardial infarction, probably by increased formation of the endogenous nucleoside adenosine. In the current research proposal, the investigators aim to translate this finding to the human in vivo situation, using flow-mediated dilation (FMD) of the brachial artery as a well-validated model of (endothelial) IR-injury.
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
- None
入排标准
- 年龄范围
- 30 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 30-50 years
- •Written informed consent
排除标准
- •Hypertension (in supine position: systolic BP > 140 mmHg, diastolic BP > 90 mmHg)
- •Hyperlipidaemia (fasting total cholesterol > 5.5 mmol/L or random > 6.5 mmol/L)
- •Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
- •History of any cardiovascular disease
- •Concomitant use of medication
- •Renal dysfunction (MDRD < 60 ml/min)
- •Professional athletes
研究组 & 干预措施
Pretreatment with metformin
Pretreatment with metformin 500 mg three times a day for 3 days.
干预措施: Metformin (Drug)
Pretreatment with Metformin/caffeine
to study whether caffeine (4 mg/kg intravenously over 10 minutes) attenuates the protective effect of metformin (500 mg three times a day for 3 days) on FMD after ischemia/reperfusion
干预措施: Pretreatment with metformin in combination of infusion of caffeine. (Drug)
No metformin, only pretreatment with caffeine
No pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes).
干预措施: No pretreatment with metformin in combination with infusion of caffeine (Drug)
结局指标
主要结局
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.
时间窗: approx. 6 months
Metformin-FMD trial: To study the effect of oral pretreatment with metformin (500 mg three times ad ay for 3 days) on flow mediated dilation of the brachial artery after 20 minutes of forearm ischemia and 20 minutes of reperfusion in healthy volunteers.
Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.
时间窗: approx. 6 months
Control trial: when metformin displays a protective effect on endothelial function, we will conduct a second experiment to study whether caffeine, an adenosine receptor antagonist, attenuates the protective effect of metformin on flow mediated dilation after 20 minutes of ischemia and 20 minutes of reperfusion in healthy volunteers.
次要结局
未报告次要终点