Official Title: “Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?”

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.

Study Type: Interventional

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

Study Primary Completion Date: October 2007

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.

Intervention(s) in this Clinical Trial

• Drug: dipyridamole
  • dipyridamole 200mg twice daily

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • first 7 day treatment with dipyridamol and at least two weeks later 7 day treatment with placebo
• Active Comparator: 2
  • first 7 day treatment with placebo and at least two weeks later 7 day treatment with atorvastatin

Primary Measures

• Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.
  • Time Frame: 60 and 240 minutes after reperfusion
    Safety Issue?: No

Secondary Measures

• Plasma dipyridamole concentration
  • Time Frame: in the morning of day seven of treatment
    Safety Issue?: No
• Workload (duration of exercise and developed force)
  • Time Frame: during 10 minutes ischemic exercise
    Safety Issue?: No
• Heart rate (preceded by a 7day treatment of dipyridamol or placebo)
  • Time Frame: during 30 minutes at day seven of treatment with dipyridamol and placebo
    Safety Issue?: No

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

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

G Rongen, MD PhD Principal Investigator RUNMC  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00457405

Study ID Number: dipy003

ClinicalTrials.gov Identifier: NCT00457405

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)