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

Sponsored by:	Radboud University
Information provided by:	Radboud University
ClinicalTrials.gov Identifier:	NCT00457405

Purpose

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.

Condition	Intervention	Phase
Ischemia-Reperfusion Injury Atherosclerosis	Drug: dipyridamole	Phase IV

MedlinePlus related topics: Exercise and Physical Fitness

Drug Information available for: Dipyridamole

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?

Further study details as provided by Radboud University:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Plasma dipyridamole concentration [ Time Frame: in the morning of day seven of treatment ] [ Designated as safety issue: No ]
Workload (duration of exercise and developed force) [ Time Frame: during 10 minutes ischemic exercise ] [ Designated as 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 ] [ Designated as safety issue: No ]

Enrollment:	10
Study Start Date:	June 2007
Study Completion Date:	March 2008
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator first 7 day treatment with dipyridamol and at least two weeks later 7 day treatment with placebo	Drug: dipyridamole dipyridamole 200mg twice daily
2: Active Comparator first 7 day treatment with placebo and at least two weeks later 7 day treatment with atorvastatin	Drug: dipyridamole dipyridamole 200mg twice daily

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00457405

Locations

Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500HB

Sponsors and Collaborators

Radboud University

Investigators

Principal Investigator:

G Rongen, MD PhD

RUNMC

More Information

Publications:

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.

Responsible Party:	dept Pharmacology Toxicology ( G Rongen )
Study ID Numbers:	dipy003
Study First Received:	April 4, 2007
Last Updated:	April 14, 2008
ClinicalTrials.gov Identifier:	NCT00457405
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:

ischemia-reperfusion injury
atherosclerosis
dipyridamole
annexin A5 targeting

Study placed in the following topic categories:

Arterial Occlusive Diseases
Atherosclerosis
Postoperative Complications
Vascular Diseases
Annexin A5

Arteriosclerosis
Ischemia
Dipyridamole
Reperfusion Injury

Additional relevant MeSH terms:

Vasodilator Agents
Phosphodiesterase Inhibitors
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Hematologic Agents

Platelet Aggregation Inhibitors
Enzyme Inhibitors
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009