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

Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: September 2007

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.

Intervention(s) in this Clinical Trial

• Drug: Rosuvastatin
  • 7 day treatment rosuvastatin 20mg

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • 7 day treatment rosuvastatin
• Placebo Comparator: 2
  • 7 day treatment placebo

Primary Measures

• The targeting of Technetium 99 labeled Annexin A5 is recorded with a gamma camera as a endpoint measure of ischemia-reperfusion damage.
  • Time Frame: 60 and 240 minutes after ischemic exercise
    Safety Issue?: No

Secondary Measures

• Workload (product of 50% of the maximum forearm force and duration of the ischemic exercise)
  • Time Frame: during 10 minutes of ischemic exercise
    Safety Issue?: No
• The effect of one-week treatment of rosuvastatin 20mg once daily on lipid spectrum.
  • Time Frame: before and after 7day treatment
    Safety Issue?: No
• The caffeine serum concentration after 24 hour abstinence .
  • Time Frame: morning after 24 hours abstinence of caffeine
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

Gerard Rongen, MD, Phd Principal Investigator UMCN st. Radboud  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00457652

Study ID Number: Rosuva01

ClinicalTrials.gov Identifier: NCT00457652

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)