To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm.
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Annexin A 5 targeting in the non dominant thenar muscle after ischemic
exercise, as a indicator for ischemia reperfusion injury
Secondary outcome
Fasting lipid profile before and after three day therapy with atorvastatin
80mg. Workload performed during ischemic exercise.
Background summary
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as
statins) have been found to reduce cardiovascular events. This protective
effect has been traditionally explained by lowering plasma cholesterol and
subsequent reduced progression of atherosclerosis. However in animal
experiments statins have also shown the ability to induce pharmacologic
preconditioning and thereby reduce infarct size. This effect contributes to the
beneficial effect of statins on reducing of cardiovascular events. In order to
differentiate between these two mechanisms of protection we will study the
effect of atorvastatin on ischemia reperfusion damage after a short exposure to
atorvastatin, before the lipid lowering effect of atorvastatin becomes
apparent.
Study objective
To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5
targeting after ischemic exercise in the non-dominant forearm.
Study design
Double blind-placebo controlled intervention study, cross-over design, single
centre.
Intervention
in a cross-over design all volunteers receive 3 day treatment with atorvastatin
80mg daily or placebo. Between the active treatment period and the placebo
period, a wash-out period of at least 4 weeks will be respected
Study burden and risks
Treatment with atorvastatin or placebo is not expected to harm the volunteers.
Most reported side effects of atorvastatin are gastro-intestinal complains and
myalgia. Ischemic hand gripping will temporarily result in pain in the forearm.
This is completely reversible upon reperfusion. Administration of radiolabeled
Annexin A5 results in an effective dose of less than 5 mSv, well within the
range of accepted exposure to radioactivity for human research. Occurrence of
an allergic reaction is theoretically possible upon administration of Annexin
A5, however there have been no allergic reaction reported in all volunteers
exposed to Annexin A5. The volunteers will not benefit directly from
participating in this study.
postbus 9101
6500 HB Nijmegen
Nederland
postbus 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
-Male
-Age 18-50 years
-Informed consent
-Physical able to perform ischemic exercise
Exclusion criteria
-History of any cardiovascular disease
-Hypertension (in supine position: systole > 140 mmHg, diastole > 90 mmHg)
-Diabetes mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
-Hyperlipidaemia (random total cholesterol > 6 mmol/l)
-Alanine-Amino-Transferase (ALAT) >90 U/L (more than twice the upper level of the normal range)
-Creatinine Kinase (CK) >340 U/L (more than twice the upper level of the normal range)
-Drug abuse
-Concomitant chronic use of medication
-Administration of radioactivity in research setting during the last 5 years
-Participation to any drug-investigation during the previous 60 days as checked with VIP check according to CRCN standard procedures
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 | EUCTR2006-006706-29-NL |
| CCMO | NL15624.091.06 |