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

NCT ID: NCT00253929

Last Updated: 2007-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-11-30

Study Completion Date

2006-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Blood Flow in Healthy Volunteers

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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Intra-arterial infusion of adenosine

Intervention Type DRUG

intra-arterial infusion of caffeine

Intervention Type DRUG

intra-arterial infusion of acetylcholine

Intervention Type DRUG

intra-arterial infusion of sodium nitroprusside

Intervention Type DRUG

Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 minutes

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 18-40 year

Exclusion Criteria

* hypertension
* diabetes
* cardiovascular or pulmonary disease
* asthma
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Principal Investigators

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Gerard Rongen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Paul Smits, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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Riksen NP, Franke B, van den Broek P, Naber M, Smits P, Rongen GA. The 22G>A polymorphism in the adenosine deaminase gene impairs catalytic function but does not affect reactive hyperaemia in humans in vivo. Pharmacogenet Genomics. 2008 Oct;18(10):843-6. doi: 10.1097/FPC.0b013e328305e630.

Reference Type DERIVED
PMID: 18794722 (View on PubMed)

Other Identifiers

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ZonMw Nr. 920-03-249

Identifier Type: -

Identifier Source: secondary_id

SNPAdenosine

Identifier Type: -

Identifier Source: org_study_id