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Adenosine Receptors Influence Ischemia-Reperfusion Injury

This study has suspended participant recruitment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00184847
First Posted: September 16, 2005
Last Update Posted: March 28, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Radboud University
  Purpose

Ischemic preconditioning is defined as the development of tolerance to ischemia-reperfusion injury by a previous short bout of ischemia resulting in a marked reduction in infarct size. This mechanism can be mimicked by several pharmacological substances such as acetylcholine and adenosine.

To detect ischemia-reperfusion injury in humans in vivo Kharbanda et al. developed a method in which endothelial dysfunction represents the effects of ischemic preconditioning. This method, however, uses acetylcholine to measure endothelial function before and after forearm ischemia. We, the investigators at Radboud University, hypothesize that the use of acetylcholine in this model reduces ischemia-reperfusion injury. Therefore, we will compare this protocol with a protocol in which endothelial function is only measured after ischemia. We expect an increase in ischemia-reperfusion injury when endothelial function is only measured after the forearm ischemia.

After determining the optimal method to measure ischemia-reperfusion injury of the vascular endothelium we will determine the effect of acute and chronic caffeine, an adenosine receptor antagonist, on ischemic preconditioning. With this study we expect to find that adenosine mimics ischemic preconditioning of the vascular endothelium. Moreover, we expect to find that acute caffeine intake reduces ischemia-reperfusion injury whereas chronic caffeine intake does not. This study will increase our knowledge about the mechanism of ischemic preconditioning and may also provide leads to exploit this endogenous protective mechanism in a clinical setting.


Condition Intervention
Ischemia-Reperfusion Injury Drug: acetylcholine Procedure: twenty minutes of forearm ischemia Procedure: three 5-minute periods of forearm ischemia Drug: adenosine Drug: caffeine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Official Title: Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia

Estimated Enrollment: 8
Study Start Date: March 2005
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00184847


Locations
Netherlands
Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Gerard Rongen, MD, PhD Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00184847     History of Changes
Other Study ID Numbers: ACAD
First Submitted: September 12, 2005
First Posted: September 16, 2005
Last Update Posted: March 28, 2008
Last Verified: March 2008

Keywords provided by Radboud University:
acetylcholine
adenosine
caffeine
ischemic preconditioning

Additional relevant MeSH terms:
Ischemia
Reperfusion Injury
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Caffeine
Adenosine
Acetylcholine
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Cholinergic Agonists
Cholinergic Agents