Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00430170
First received: January 31, 2007
Last updated: July 28, 2008
Last verified: July 2008
  Purpose

The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.


Condition Intervention Phase
Cardiovascular Disease
Ischemia-Reperfusion Injury
Drug: Dipyridamole
Drug: caffeine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion [ Time Frame: 60 and 240 minutes after ischemic exercise ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma dipyridamole concentration [ Time Frame: at the morning of day 7 of treatment with dipyridamole/placebo ] [ Designated as safety issue: No ]
  • ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days) [ Time Frame: before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol) ] [ Designated as safety issue: No ]
  • Workload (duration of exercise and developed force) [ Time Frame: during 10 minutes of ischemic exercise ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: January 2007
Study Completion Date: April 2007
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
Drug: Dipyridamole
Dipyridamole 2x200mg 7day per os
Other Name: persatin
Drug: caffeine
caffeine 4mg/kg iv
Other Name: n.a.
Placebo Comparator: 2
dipyridamol during 7 days and before ischemic exercise placebo
Drug: Dipyridamole
Dipyridamole 2x200mg 7day per os
Other Name: persatin

Detailed Description:

Dipyridamole has been proven to reduce targeting of Annexin A5 in responses to ischemic exercise, indicating protection against ischemia-reperfusion injury in humans (pharmacological preconditioning). Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury. We hypothesize that endogenous adenosine mediates the protective effect of dipyridamole against ischemia-reperfusion injury. Therefore the adenosine receptor antagonist caffeine will reduce the benefit of dipyridamole on forearm ischemia-reperfusion injury.

  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 (random total cholesterol > 6.5 mmol/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 two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00430170

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500hb
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Gerard Rongen, MD PhD Radboud University
  More Information

Publications:
Responsible Party: G Rongen, dept Pharmacology Toxicology
ClinicalTrials.gov Identifier: NCT00430170     History of Changes
Other Study ID Numbers: dipy001
Study First Received: January 31, 2007
Last Updated: July 28, 2008
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
ischemia-reperfusion injury
adenosine
dipyridamole
caffeine

Additional relevant MeSH terms:
Cardiovascular Diseases
Ischemia
Reperfusion Injury
Pathologic Processes
Postoperative Complications
Vascular Diseases
Caffeine
Dipyridamole
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Stimulants
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 29, 2014