Clinical trial NCT00457652: Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?
Official title: Does Caffeine Reduce Rosuvastatin-Induced Protection Against Ischemia-Reperfusion Injury?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemia Reperfusion Injury
Keywords: Rosuvastatin
Caffeine
Ischemia
Reperfusion
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2007-04-06
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Does caffeine reduce rosuvastatin induced protection against ischemia reperfusion injury?

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 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

Primary outcomes:
measure: The targeting of Technetium 99 labeled Annexin A5 is recorded with a gamma camera as a endpoint measure of ischemia-reperfusion damage.
timeFrame: 60 and 240 minutes after ischemic exercise
Secondary outcomes:
measure: Workload (product of 50% of the maximum forearm force and duration of the ischemic exercise)
timeFrame: during 10 minutes of ischemic exercise
measure: The effect of one-week treatment of rosuvastatin 20mg once daily on lipid spectrum.
timeFrame: before and after 7day treatment
measure: The caffeine serum concentration after 24 hour abstinence .
timeFrame: morning after 24 hours abstinence of caffeine
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: UMCN st.Radboud
Study officials:
affiliation: UMCN st. Radboud
name: Gerard Rongen, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
citation: 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. doi: 10.1161/ATVBAHA.108.179622. Epub 2009 Apr 9.