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Effect of Polymorphisms in the Adenosine a2a Receptor Gene and AMPD2 Gene on Adenosine-Induced Vasodilation and Reactive Hyperemia

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00253929
First Posted: November 15, 2005
Last Update Posted: April 5, 2007
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.
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
Radboud University
  Purpose
The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral effects by stimulation of specific adenosine receptors. taken together these effects protect against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes involved in the formation or breakdown of adenosine could potentially modulate these effects. In this study, we aim to determine the functional effects of two frequent genetic polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of adenosine) on the vascular effects of adenosine.

Condition Intervention
Blood Flow in Healthy Volunteers Drug: Intra-arterial infusion of adenosine Drug: intra-arterial infusion of caffeine Drug: intra-arterial infusion of acetylcholine Drug: intra-arterial infusion of sodium nitroprusside Procedure: Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 minutes

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: The Influence of the 1976T>C Polymorphism in the Adenosine A2A Receptor Gene on Adenosine-Induced Vasodilation and the Influence of the 34C>T Polymorphism in the AMP Deaminase Gene on Post-Occlusive Reactive Hyperemia.

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • A2A: adenosine- and caffeine induced vasomotion (blood flow)
  • AMPD:post-occlusive reactibe hyperemic blood flow

Estimated Enrollment: 100
Study Start Date: November 2005
Estimated Study Completion Date: February 2006
Detailed Description:

The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral effects by stimulation of specific adenosine receptors. taken together these effects protect against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes involved in the formation or breakdown of adenosine could potentially modulate these effects. In this study, we aim to determine the functional effects of two frequent genetic polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of adenosine) on the vascular effects of adenosine.

In 100 healthy young volunteers, we will determine the genotype of the adenosine A2A receptor gene. We expect to find approximately 15 subjects with the 1976T>C polymorphisms. It is known that this polymorphism is associated with an increased neuropsychological sensitivity to caffeine administration.

We will explore whether this polymorphism is associated with a different vasodilating response to the administration of adenosine and caffeine into the brachial artery. Blood flow will be measured with venous occlucion plethysmography.

Secondly, we will also determine the genotype of the AMPD1 gene. We expect to find 15 subjects with the 34C>T mutation, which is a loss-of-function-mutation. Cardiovascular patients with this mutation are known to have a survival benefit. We will explore whether the post-occlusive reactive hyperemia in the forearm is potentiated, because during ischaemia, more adenosine is formed in these subjects.

  Eligibility

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-40 year

Exclusion Criteria:

  • hypertension
  • diabetes
  • cardiovascular or pulmonary disease
  • asthma
  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): NCT00253929


Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Gerard Rongen, MD, PhD Radboud University
Principal Investigator: Paul Smits, MD, PhD Radboud University
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00253929     History of Changes
Other Study ID Numbers: SNPAdenosine
ZonMw Nr. 920-03-249
First Submitted: November 11, 2005
First Posted: November 15, 2005
Last Update Posted: April 5, 2007
Last Verified: February 2006

Keywords provided by Radboud University:
adenosine
polymorphisms
blood flow
adenosine A2a receptor
AMP deaminase

Additional relevant MeSH terms:
Hyperemia
Vascular Diseases
Cardiovascular Diseases
Caffeine
Adenosine
Acetylcholine
Nitroprusside
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
Antihypertensive Agents
Nitric Oxide Donors
Cholinergic Agonists
Cholinergic Agents