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Sponsors and Collaborators: |
Radboud University ZonMw: The Netherlands Organisation for Health Research and Development |
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Information provided by: | Radboud University |
ClinicalTrials.gov Identifier: | NCT00253929 |
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 |
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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: | Diagnostic, Non-Randomized, Open Label, Active Control, Parallel Assignment, Pharmacodynamics Study |
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. |
Estimated Enrollment: | 100 |
Study Start Date: | November 2005 |
Estimated Study Completion Date: | February 2006 |
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.
Ages Eligible for Study: | 18 Years to 40 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Netherlands, Gelderland | |
Radboud University Nijmegen Medical Centre | |
Nijmegen, Gelderland, Netherlands, 6500HB |
Principal Investigator: | Gerard Rongen, MD, PhD | Radboud University |
Principal Investigator: | Paul Smits, MD, PhD | Radboud University |
Study ID Numbers: | SNPAdenosine, ZonMw Nr. 920-03-249 |
Study First Received: | November 11, 2005 |
Last Updated: | April 4, 2007 |
ClinicalTrials.gov Identifier: | NCT00253929 |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
adenosine polymorphisms blood flow adenosine A2a receptor AMP deaminase |
Nitric Oxide Caffeine citrate Hyperemia Nitroprusside Vascular Diseases |
Caffeine Acetylcholine Healthy Adenosine |
Neurotransmitter Agents Vasodilator Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Cardiovascular Agents Antihypertensive Agents Cholinergic Agents Pharmacologic Actions |
Nitric Oxide Donors Sensory System Agents Therapeutic Uses Cardiovascular Diseases Anti-Arrhythmia Agents Analgesics Peripheral Nervous System Agents Central Nervous System Agents |