The Metformin-FMD Trial (MetFMD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01610401
First received: May 25, 2012
Last updated: May 17, 2013
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Ischemia Reperfusion Injury
Endothelial Function
Drug: Metformin
Drug: Pretreatment with metformin in combination of infusion of caffeine.
Drug: No pretreatment with metformin in combination with infusion of caffeine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Can Metformin Prevent Endothelial Ischemia and Reperfusion Injury? The Metformin-FMD Trial

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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. [ Time Frame: approx. 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 26
Study Start Date: May 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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).

  Eligibility

Ages Eligible for Study:   30 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610401

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: N. Riksen, MD, PhD Radboud University
Principal Investigator: G.A. Rongen, M.D. Radboud University
Principal Investigator: D.H. Thijssen, PhD Radboud University
  More Information

No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01610401     History of Changes
Other Study ID Numbers: Metformin-FMD 001
Study First Received: May 25, 2012
Last Updated: May 17, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Metformin
Caffeine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 16, 2014