The Metformin-FMD Trial

NCT01610401 | Completed Phase 4

• 1 other identifier: Metformin-FMD 001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemia Reperfusion Injury; Endothelial Function

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (4)

Pretreatment with metformin

ACTIVE COMPARATOR

Pretreatment with metformin 500 mg three times a day for 3 days.

Drug: Metformin

No pretreatment.

NO INTERVENTION

no intervention

Pretreatment with Metformin/caffeine

ACTIVE COMPARATOR

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.

No metformin, only pretreatment with caffeine

OTHER

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

Interventions

Metformin DRUG

metformin 500 mg three times a day, for 3 days

Pretreatment with metformin

Pretreatment with metformin in combination of infusion of caffeine. DRUG

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

Pretreatment with Metformin/caffeine

No pretreatment with metformin in combination with infusion of caffeine DRUG

No pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes).

No metformin, only pretreatment with caffeine

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 30-50 years
• Written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Publications (1)

• El Messaoudi S, Schreuder TH, Kengen RD, Rongen GA, van den Broek PH, Thijssen DH, Riksen NP. Impact of metformin on endothelial ischemia-reperfusion injury in humans in vivo: a prospective randomized open, blinded-endpoint study. PLoS One. 2014 Apr 22;9(4):e96062. doi: 10.1371/journal.pone.0096062. eCollection 2014.

  PMID: 24755906 DERIVED

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Metformin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• N. Riksen, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• G.A. Rongen, M.D.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• D.H. Thijssen, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2012
• First Posted: June 4, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 20, 2013

Record last verified: 2012-02

Locations

NL (1)