Clinical trial NCT00430170: Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Official title: Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Disease
Ischemia-Reperfusion Injury
Keywords: ischemia-reperfusion injury
adenosine
dipyridamole
caffeine
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2007-02-01
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.

Detailed description: Dipyridamole has been proven to reduce targeting of Annexin A5 in responses to ischemic exercise, indicating protection against ischemia-reperfusion injury in humans (pharmacological preconditioning). Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury. We hypothesize that endogenous adenosine mediates the protective effect of dipyridamole against ischemia-reperfusion injury. Therefore the adenosine receptor antagonist caffeine will reduce the benefit of dipyridamole on forearm ischemia-reperfusion injury.

Eligibility criteria: Inclusion Criteria:

* Male
* Age between 18-50yr.

Exclusion Criteria:

* cardiovascular disease
* hypertension (systole \> 140 mmHg, diastole \> 90 mmHg)
* hypercholesterolemia (random total cholesterol \> 6.5 mmol/l)
* diabetes mellitus (fasting glucose \> 7.0 mmol/L or random glucose \> 11.0 mmol/L)
* asthma (recurrent episodes of dyspnea and wheezing, or usage of prescribed inhalation medication: i.e. corticosteroids or B2-agonists)
* participation in any clinical trial during the last 60 days prior to this study.
* administration of two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.

Primary outcomes:
measure: Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion
timeFrame: 60 and 240 minutes after ischemic exercise
Secondary outcomes:
measure: Plasma dipyridamole concentration
timeFrame: at the morning of day 7 of treatment with dipyridamole/placebo
measure: ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)
timeFrame: before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol)
measure: Workload (duration of exercise and developed force)
timeFrame: during 10 minutes of ischemic exercise
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Gerard Rongen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riksen NP, Oyen WJ, Ramakers BP, Van den Broek PH, Engbersen R, Boerman OC, Smits P, Rongen GA. Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans. Clin Pharmacol Ther. 2005 Jul;78(1):52-9. doi: 10.1016/j.clpt.2005.03.003.
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.