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

Phase 4

Completed

• Conditions: Cardiovascular Disease; Ischemia-Reperfusion Injury
• Interventions: Drug: Dipyridamole; Drug: caffeine

• Registration Number: NCT00430170
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2007-01-31
• Study First Submitted QC: 2007-01-31
• Study First Posted: 2007-02-01
• Primary Completion: 2007-03
• Study Completion: 2007-04
• Status Verified: 2008-07
• Last Update Submitted: 2008-07-28
• Last Update Posted: 2008-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Dipyridamole	dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
1	caffeine	dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
2	Dipyridamole	dipyridamol during 7 days and before ischemic exercise placebo

Primary Outcome Measures

Name	Time	Method
Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion	60 and 240 minutes after ischemic exercise

Secondary Outcome Measures

Name	Time	Method
Plasma dipyridamole concentration	at the morning of day 7 of treatment with dipyridamole/placebo
ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)	before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol)
Workload (duration of exercise and developed force)	during 10 minutes of ischemic exercise

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands