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

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00457652
First received: April 4, 2007
Last updated: April 14, 2008
Last verified: April 2008
  Purpose

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00457652

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: G Rongen, dept Pharmacology toxicology UMCN
ClinicalTrials.gov 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:
Rosuvastatin
Caffeine
Ischemia
Reperfusion

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Rosuvastatin
Caffeine
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses
Central Nervous System Stimulants
Physiological Effects of Drugs
Central Nervous System Agents
Phosphodiesterase Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on October 01, 2014