To study the protective effect of pre-treatment with metformin on flow mediated dilation after 20 minutes ischemia and 20 minutes reperfusion. If metformin treatment indeed limits endothelial IR-injury, a second study will be performed in the same…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in flow mediated dilation before and after 20 minutes of ischemia.
Secondary outcome
not applicable.
Background 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, we 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 objective
To study the protective effect of pre-treatment with metformin on flow mediated
dilation after 20 minutes ischemia and 20 minutes reperfusion. If metformin
treatment indeed limits endothelial IR-injury, a second study will be performed
in the same subjects to investigate whether this is mediated by adenosine
receptor stimulation.
Study design
Randomized, open label, cross over clinical trial.
Intervention
Main study (metformin FMD trial): Pre-treatment with metformin 500 mg three
times a day for 3 days or no treatment. Second study: Pre-treatment with
metformin 500 mg three times a day for 3 days or no treatment, combined with
caffeine infusion preceding FMD measurement.
Study burden and risks
Healthy volunteers will be treated with metformin (500mg three times a day) for
3 days. Short-term treatment with metformin is not expected to induce serious
side-effects. Monotherapy with metformin does not induce hypoglycemia.
Metformin can give some gastrointestinal discomfort in the first days of
treatment, but this is mild and self-limiting. Lactic acidosis is a rare, but
serious, complication of metformin, which can occur in the setting of
shock/hypoxia/renal failure in combination with metformin accumulation. This is
therefore not to be expected in case of healthy volunteers. The participants
will not benefit directly from participating in this study, but if our
hypothesis proves to be correct, these findings will help to optimize future
medical care of patients suffering from (myocardial) ischemia/infarction.
Postbus 9101
6500 HB
NL
Postbus 9101
6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Age 30-50 years
- Written informed consent
Exclusion criteria
- Smoking
- Hypertension (Psystole > 140mmHg, diastole > 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 chronic use of medication
- Renal dysfunction (MDRD < 60 ml/min)
- Professional athletes
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005343-27-NL |
| CCMO | NL38672.091.11 |