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:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00253929
First received: November 11, 2005
Last updated: April 4, 2007
Last verified: February 2006
  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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-40 year

Exclusion Criteria:

  • hypertension
  • diabetes
  • cardiovascular or pulmonary disease
  • asthma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided by Radboud University

Additional 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
Study First Received: November 11, 2005
Last Updated: April 4, 2007
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

Additional relevant MeSH terms:
Acetylcholine
Adenosine
Nitroprusside
Analgesics
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nitric Oxide Donors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 29, 2014