Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Study Overview
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Brief Summary
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To study the impact of 3 day exposure to atorvastatin 80mg on Annexin A5 targeting after ischemic exercise in the non-dominant forearm.

Detailed Description
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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.

Official Title
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Does Atorvastatin Reduce Ischemia-Reperfusion Injury in Humans in-Vivo?

Conditions
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Ischemia Reperfusion Injury, Cardiovascular Disease

Intervention / Treatment
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* Drug: atorvastatin


Participation Criteria
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Eligibility Criteria
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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 (fasting total cholesterol > 5.5 mmol/l) Alanine-Amino-Transferase (ALAT) >90 U/L Creatinine Kinase (CK) >440 U/L Drug or alcohol abuse Concommitant 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>first 3 day treatment placebo and 4 weeks later three day treatment with atorvastatin 80 mg | Drug: atorvastatin<br>* atorvastatine 80mg, during 3 days<br>* Other names: lipitor;|
| Active Comparator: 2<br>first 3 day treatment atorvastatin 80 mg and 4 weeks later three day treatment with placebo | Drug: atorvastatin<br>* atorvastatine 80mg, during 3 days<br>* Other names: lipitor;|
| No Intervention: 3<br>3 days treatment with placebo twice | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annexin A 5 targeting in the non dominant thenar muscle after ischemic exercise, as a indicator for ischemia reperfusion injury. |  | 60 and 240 minutes after ischemic exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| workload during ischemic exercise |  | workload during 10minutes of ischemic exercise | 
| effect of 3-day treatment with atorvastatin 80mg daily on serum lipid levels |  | fasting lipid levels before and at first day after 3 day treatment with atorvastatin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemia reperfusion injury, atorvastatine, preconditioning, cardiovascular disease