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

Ischemia Reperfusion Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00457652
• Other study ID #: Rosuva01
• Status: Completed
• Phase: Phase 4
• First received: April 4, 2007
• Last updated: April 14, 2008
• Start date: June 2007
• Est. completion date: November 2007

Study information

• Verified date: April 2008
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ischemia
• Ischemia Reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• Rosuvastatin
7 day treatment rosuvastatin 20mg

Locations

Country	Name	City	State
Netherlands	UMCN st.Radboud	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

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