Clinical Trial on Acetylcholine, Adenosine, Intra-arterial infusion of adenosine, intra-arterial infusion of caffeine, intra-arterial infusion of acetylcholine, intra-arterial infusion of sodium nitroprusside - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Blood Flow in Healthy Volunteers

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

100

Phase

Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Netherlands
- Gelderland
  - Nijmegen, Gelderland, Netherlands, 6500HB
    - Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 36 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

18-40 year

Exclusion Criteria:

hypertension
diabetes
cardiovascular or pulmonary disease
asthma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

Principal Investigator: Gerard Rongen, MD, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Study Completion

February 1, 2006

Study Registration Dates

First Submitted

November 11, 2005

First Submitted That Met QC Criteria