The Metformin-FMD Trial

Phase 4

Completed

• Conditions: Ischemia Reperfusion Injury; Endothelial Function
• Interventions: Drug: Pretreatment with metformin in combination of infusion of caffeine.; Drug: No pretreatment with metformin in combination with infusion of caffeine; Drug: Metformin

• Registration Number: NCT01610401
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2012-02
• Study Start: 2012-05
• Study First Submitted: 2012-05-25
• Study First Submitted QC: 2012-06-01
• Study First Posted: 2012-06-04
• Primary Completion: 2013-01
• Study Completion: 2013-01
• Last Update Submitted: 2013-05-17
• Last Update Posted: 2013-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Age 30-50 years
• Written informed consent

Read More

Exclusion Criteria

• Smoking
• 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Pretreatment with Metformin/caffeine	Pretreatment with metformin in combination of infusion of 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
No metformin, only pretreatment with caffeine	No pretreatment with metformin in combination with infusion of caffeine	No pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes).
Pretreatment with metformin	Metformin	Pretreatment with metformin 500 mg three times a day for 3 days.

Primary Outcome Measures

Name	Time	Method
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.	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.	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.

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Gelderland, Netherlands