The Metformin-FMD Trial (MetFMD)

Radboud University Medical Center

Status and phase: Completed; Phase 4

Conditions: Endothelial Function; Ischemia Reperfusion Injury

Treatments: Drug: No pretreatment with metformin in combination with infusion of caffeine; Drug: Metformin; Drug: Pretreatment with metformin in combination of infusion of caffeine.

Study type: Interventional

Funder types: Other

Identifiers

NCT01610401

Metformin-FMD 001

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 30 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

26 participants in 4 patient groups

Pretreatment with metformin

Active Comparator group

Description:

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

Treatment:

Drug: Metformin

No pretreatment.

No Intervention group

Description:

no intervention

Pretreatment with Metformin/caffeine

Active Comparator group

Description:

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

Treatment:

Drug: Pretreatment with metformin in combination of infusion of caffeine.

No metformin, only pretreatment with caffeine

Other group

Description:

No pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes).

Treatment:

Drug: No pretreatment with metformin in combination with infusion of caffeine