Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?

Study Overview
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Brief Summary
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Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

Detailed Description
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Rosuvastatin is a proven cholesterol lowering medicine, which hereby is assumed to achieve a reduction in cardiovascular events. Apart from it's cholesterol lowering action, rosuvastatin may also increase tolerance against ischemia-reperfusion injury. In dogs rosuvastatin increases the endogenous concentration of adenosine, by enhancing the activity of the enzyme ecto-5'-nucleotidase, which converts adenosine monophosphate into adenosine. We hypothesize that rosuvastatin increases tolerance against ischemia-reperfusion injury by induction of ecto-5'-nucleotidase and thereby increasing adenosine activity. This protective effect of rosuvastatin can be abrogated by using the adenosine receptor antagonist caffeine.

Official Title
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Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?

Conditions
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Ischemia Reperfusion Injury

Intervention / Treatment
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* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male age between 18-50 yrs signed informed consent Exclusion Criteria: Cardiovascular disease Hypertension (systole > 140 mmHg, diastole > 90 mmHg) Hypercholesterolemia (fasting total cholesterol > 6,0 mmol/l) Drug abuse Concomitant medication use Inability to perform the ischemic isometric muscle contraction Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L) Alanine-Amino-Transferase (ALAT) >90U/L (more than twice the upper level of the normal range) Creatinine Kinase (CK) >340U/L (more than twice the upper level of the normal range) Participation in any trial concerning medicinal products during the last 60 days prior to this study. Participation in clinical trial involving

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>7 day treatment rosuvastatin | Drug: Rosuvastatin<br>* 7 day treatment rosuvastatin 20mg<br>|
| Placebo Comparator: 2<br>7 day treatment placebo | Drug: Rosuvastatin<br>* 7 day treatment rosuvastatin 20mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The targeting of Technetium 99 labeled Annexin A5 is recorded with a gamma camera as a endpoint measure of ischemia-reperfusion damage. |  | 60 and 240 minutes after ischemic exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Workload (product of 50% of the maximum forearm force and duration of the ischemic exercise) |  | during 10 minutes of ischemic exercise | 
| The effect of one-week treatment of rosuvastatin 20mg once daily on lipid spectrum. |  | before and after 7day treatment | 
| The caffeine serum concentration after 24 hour abstinence . |  | morning after 24 hours abstinence of caffeine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rosuvastatin, Caffeine, Ischemia, Reperfusion