The Metformin-FMD Trial

Endothelial Function Clinical Trial

— MetFMD  

Official title:

Can Metformin Prevent Endothelial Ischemia and Reperfusion Injury? The Metformin-FMD Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01610401
• Other study ID #: Metformin-FMD 001
• Status: Completed
• Phase: Phase 4
• First received: May 25, 2012
• Last updated: May 17, 2013
• Start date: May 2012
• Est. completion date: January 2013

Study information

• Verified date: February 2012
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 50 Years

Eligibility

Inclusion Criteria:

• Age 30-50 years

• Written informed consent

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endothelial Function
• Ischemia
• Ischemia Reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• Metformin
metformin 500 mg three times a day, for 3 days
• Pretreatment with metformin in combination of infusion of caffeine.
Pretreatment with metformin 500 mg three times a day for 3 days, in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes) prior to FMD measurement
• No pretreatment with metformin in combination with infusion of caffeine
No pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes).

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.	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.	approx. 6 months	No
Primary	Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.	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.	approx. 6 months	No