Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?

Atherosclerosis Clinical Trial

Official title:

Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00457405
• Other study ID #: dipy003
• Status: Completed
• Phase: Phase 4
• First received: April 4, 2007
• Last updated: April 14, 2008
• Start date: June 2007
• Est. completion date: March 2008

Study information

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

Clinical Trial Summary

This study is performed to determine whether a seven day treatment with dipyridamole (slow release, 200mg twice daily) can induce a protective effect against ischemia-reperfusion injury, after ischemic exercise of the non-dominant forearm in healthy volunteers.

Description:

Rationale:

Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury (pharmacologic preconditioning).

The purpose of this project is to explore whether a seven day treatment with dipyridamole can reduce ischemia-reperfusion injury in the forearm, in a randomized double blind placebo controlled trial.

Study design:

Randomized double-blind placebo-controlled trial with a cross-over design.

Study population:

Healthy male volunteers, aged 18-50 yr

Intervention:

10 Volunteers will be randomised to receive in a cross-over design either a 7 day treatment with dipyridamole (Persantin retard; 200 mg twice daily) or placebo followed by 10 minutes of ischemic isometric muscle contraction of the non-dominant forearm and upon reperfusion infusion of radiolabeled Annexin A5 (Annexin scintigraphy).

Main study parameters/endpoints:

Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

This study will be executed at the Clinical Research Centre Nijmegen under close medical supervision. Treatment with dipyridamole is not expected to harm the volunteers. During the first days of treatment with dipyridamole, a headache may occur. Ischemic hand gripping will temporarily result in pain in the forearm. This is completely reversible upon reperfusion. Administration of radiolabeled Annexin A5 results in an effective dose of less than 5 mSv, well within the range of accepted exposure to radioactivity for human research. Participation in this research does not interfere with possible diagnostic or therapeutic procedures with X-rays of radioactivity in the future.

Occurrence of an allergic reaction is theoretically possible upon administration of Annexin A5, however there have been no allergic reactions reported in all volunteers exposed to Annexin A5.

The volunteers will not benefit directly from participating in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2008
• Est. primary completion date: October 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 (fasting total cholesterol > 5.5 mmol/l or not fasting total cholesterol > 6.5mmol/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 any radioactivity for research purposes during the last 5 years prior to this study.

• concomitant medication

Study Design

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

Related Conditions & MeSH terms

• Atherosclerosis
• Ischemia
• Ischemia-Reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• dipyridamole
dipyridamole 200mg twice daily

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 (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.		60 and 240 minutes after reperfusion	No
Secondary	Plasma dipyridamole concentration		in the morning of day seven of treatment	No
Secondary	Workload (duration of exercise and developed force)		during 10 minutes ischemic exercise	No
Secondary	Heart rate (preceded by a 7day treatment of dipyridamol or placebo)		during 30 minutes at day seven of treatment with dipyridamol and placebo	No