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

Cardiovascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00430170
• Other study ID #: dipy001
• Status: Completed
• Phase: Phase 4
• First received: January 31, 2007
• Last updated: July 28, 2008
• Start date: January 2007
• Est. completion date: April 2007

Study information

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

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Ischemia
• Ischemia-Reperfusion Injury
• Reperfusion Injury

Intervention

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

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View 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. Epub 2004 Dec 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Plasma dipyridamole concentration		at the morning of day 7 of treatment with dipyridamole/placebo	No
Secondary	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)	No
Secondary	Workload (duration of exercise and developed force)		during 10 minutes of ischemic exercise	No