To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm. This to confirm results from our previous study.
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
workload during ischemic exercise, effect of 3-day treatment with atorvastatin
80mg daily on serum lipid levels
Background summary
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (better 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. A recent
study showed an reduction of Annexin A5 targeting (as marker for
ischemia-reperfusion injury) after a 7 day treatment with rosuvastatin 20mg.
Furthermore a recent cross-over study on the effect of short (3 day)
atorvastatin treatment on ischemia-reperfusion injury showed a possible
carry-over effect from the active treatment to the placebo treatment (with a
minimal interval of four weeks between both study arms). Possibly this
carry-over effect indicates an prolonged protective effect of atorvastatin
treatment on ischemia-reperfusion injury. In this project we study the acute
and prolonged protective effect of a 3 day treatment with atorvastatin on
ischemia-reperfusion injury.
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. This to confirm
results from our previous study.
Study design
Randomised double-blind placebo-controlled trial, in a cross-over design.
Intervention
in a cross-over design 12 volunteers will be randomised to receive 3 day
treatment with atorvastatin 80mg daily or placebo, furthermore 6 participants
will be randomised to receive placebo twice (as a time-control experiment).
Between the first and second study 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,
though is completely reversible upon reperfusion. Administration of
radiolabeled Annexin A5 twice results in an effective dose approximately 10mSv,
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 (over 200) exposed to Annexin A5. The volunteers
will not benefit directly from participating in this study.
postbus 9101
6500 HB Nijmegen
NL
postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
- Male
- Age 18-50 years
- Informed consent
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 (fasting total cholesterol > 5.0 mmol/l or random total cholesterol >6.5mmol/l)
-Alanine-Amino-Transferase (ALAT) >90 U/L (more than twice the upper level of the normal range)
-Creatinine Kinase (CK) >440 U/L (more than twice the upper level of the normal range)
-Glomerular filtration rate <60ml/min/1.72m2 (assessed using MDRD calculation using gender, age and serum creatinine level)
-Overt clinical signs of hypothyreoidy
-Concomitant chronic use of medication
-Administration of radioactivity for research purposes 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 | EUCTR2007-005789-11-NL |
| CCMO | NL20233.091.07 |