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

NCT ID: NCT00457405

Last Updated: 2008-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2008-03-31

Brief 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.

Detailed 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.

Conditions

Ischemia-Reperfusion Injury; Atherosclerosis

Keywords

ischemia-reperfusion injury; atherosclerosis; dipyridamole; annexin A5 targeting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

first 7 day treatment with dipyridamol and at least two weeks later 7 day treatment with placebo

Group Type: ACTIVE_COMPARATOR

dipyridamole

Intervention Type: DRUG

dipyridamole 200mg twice daily

2

first 7 day treatment with placebo and at least two weeks later 7 day treatment with atorvastatin

Group Type: ACTIVE_COMPARATOR

dipyridamole

Intervention Type: DRUG

dipyridamole 200mg twice daily

Interventions

dipyridamole

dipyridamole 200mg twice daily

Intervention Type: DRUG

Other Intervention Names

persantin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dept Pharmacology Toxicology

Principal Investigators

G Rongen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

RUNMC

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 16003293 (View on PubMed)

Other Identifiers

dipy003

Identifier Type: -

Identifier Source: org_study_id