The Metformin-FMD Trial (MetFMD)

May 17, 2013 updated by: Radboud University Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Pretreatment with metformin
Pretreatment with metformin 500 mg three times a day for 3 days.
Drug: Metformin
metformin 500 mg three times a day, for 3 days
NO_INTERVENTION: No pretreatment.
no intervention
ACTIVE_COMPARATOR: 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
Drug: 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
OTHER: 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).
Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metformin-FMD trial: The effect of pretreatment with metformin on FMD of the brachial artery after forearm ischemia and reperfusion.
Time Frame: 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.
approx. 6 months
Control trial: the effect of caffeine on the protective effect of metformin on FMD after ischemia and reperfusion.
Time Frame: 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.
approx. 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: G.A. Rongen, M.D., Radboud University Medical Center
  • Principal Investigator: D.H. Thijssen, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

January 1, 2013

Study Registration Dates

First Submitted

May 25, 2012

First Submitted That Met QC Criteria

June 1, 2012

First Posted (ESTIMATE)

June 4, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

May 20, 2013

Last Update Submitted That Met QC Criteria

May 17, 2013

Last Verified

February 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Metformin-FMD 001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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