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

This study has been completed.
Information provided by:
Radboud University Identifier:
First received: April 4, 2007
Last updated: April 14, 2008
Last verified: April 2008
Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

Condition Intervention Phase
Ischemia Reperfusion Injury
Drug: Rosuvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?

Resource links provided by NLM:

Further study details as provided by Radboud University:

Primary Outcome 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 ] [ Designated as safety issue: No ]

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

Enrollment: 24
Study Start Date: June 2007
Study Completion Date: November 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
7 day treatment rosuvastatin
Drug: Rosuvastatin
7 day treatment rosuvastatin 20mg
Placebo Comparator: 2
7 day treatment placebo
Drug: Rosuvastatin
7 day treatment rosuvastatin 20mg

Detailed Description:
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.

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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
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Please refer to this study by its identifier: NCT00457652

UMCN st.Radboud
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Principal Investigator: Gerard Rongen, MD, Phd UMCN st. Radboud
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: G Rongen, dept Pharmacology toxicology UMCN Identifier: NCT00457652     History of Changes
Other Study ID Numbers: Rosuva01 
Study First Received: April 4, 2007
Last Updated: April 14, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

Additional relevant MeSH terms:
Reperfusion Injury
Cardiovascular Diseases
Pathologic Processes
Postoperative Complications
Vascular Diseases
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on May 03, 2016