Official Title: “Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: March 2007

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.

Intervention(s) in this Clinical Trial

• Drug: Dipyridamole
  • Dipyridamole 2x200mg 7day per os
• Drug: caffeine
  • caffeine 4mg/kg iv

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
• Placebo Comparator: 2
  • dipyridamol during 7 days and before ischemic exercise placebo

Primary Measures

• Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion
  • Time Frame: 60 and 240 minutes after ischemic exercise
    Safety Issue?: No

Secondary Measures

• Plasma dipyridamole concentration
  • Time Frame: at the morning of day 7 of treatment with dipyridamole/placebo
    Safety Issue?: No
• ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)
  • Time Frame: before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol)
    Safety Issue?: No
• Workload (duration of exercise and developed force)
  • Time Frame: during 10 minutes of ischemic exercise
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

Gerard Rongen, MD PhD Principal Investigator Radboud University  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00430170

Study ID Number: dipy001

ClinicalTrials.gov Identifier: NCT00430170

Health Authority: Netherlands: Medical Ethics Review Committee (METC)