Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?
Condition: Ischemia-Reperfusion Injury; Atherosclerosis
MeSH terms: Atherosclerosis; Reperfusion Injury; Ischemia; Wounds and Injuries
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): dipyridamole
Intervention type(s): Drug
Intervention description(s): dipyridamole 200mg twice daily
Other intervention name(s): persantin
Intervention MeSH terms: Dipyridamole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ischemia-reperfusion injury; atherosclerosis; dipyridamole; annexin A5 targeting