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

Sponsor:	Radboud University
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00457652

Purpose

Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

Condition	Intervention	Phase
Ischemia Reperfusion Injury	Drug: Rosuvastatin	Phase IV

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:

MedlinePlus related topics: Caffeine

Drug Information available for: 3,7-Dihydro-1,3,7-trimethyl-1H-purine-2,6-dione Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

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

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:

Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. Epub 2004 Dec 27.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Meijer P, Oyen WJ, Dekker D, van den Broek PH, Wouters CW, Boerman OC, Scheffer GJ, Smits P, Rongen GA. Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):963-8. Epub 2009 Apr 9.

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
Caffeine
Rosuvastatin
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on February 09, 2012