Effect of Polymorphisms in the Adenosine a2a Receptor Gen... | NCT00253929

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

NCT00253929

Sponsor

Radboud University Medical Center

Status

Completed

Last Update Posted

Apr 5, 2007Estimated

Enrollment

100

Phase

Not Applicable

Conditions

Blood Flow in Healthy Volunteers

Interventions

Intra-arterial infusion of adenosine
intra-arterial infusion of caffeine
intra-arterial infusion of acetylcholine
intra-arterial infusion of sodium nitroprusside
Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 minutes

Countries

Netherlands

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

ID	Type	Description	Link
ZonMw Nr. 920-03-249

Status Module

Record Verification Date

Feb 2006

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Nov 2005

Primary Completion Date

Not provided

Completion Date

Feb 2006

First Submitted Date

Nov 11, 2005

First Submission Date that Met QC Criteria

Nov 11, 2005

First Posted Date

Nov 15, 2005Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Apr 4, 2007

Last Update Posted Date

Apr 5, 2007Estimated

Sponsor/Collaborators Module

Responsible Party, by Official Title

Not provided

Lead Sponsor

Radboud University Medical CenterOTHER

Collaborators

Name	Class
ZonMw: The Netherlands Organisation for Health Research and Development	OTHER

Description Module

Brief Summary

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

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

100

Arms/Interventions Module

Arm Groups

Not provided

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Intra-arterial infusion of adenosine	Drug
intra-arterial infusion of caffeine	Drug
intra-arterial infusion of acetylcholine	Drug
intra-arterial infusion of sodium nitroprusside	Drug
Occlusion of arm-circulation by inflation of upper-arm cuff to 200mmHg for 2, 5 and 13 minutes	Procedure

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

18-40 year

Exclusion Criteria:

hypertension
diabetes
cardiovascular or pulmonary disease
asthma

Accepts Healthy Volunteers

Yes

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

40 Years

Standard Ages

Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Gerard Rongen, MD, PhD	Radboud University Medical Center	Principal Investigator
Paul Smits, MD, PhD	Radboud University Medical Center	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Radboud University Nijmegen Medical Centre		Nijmegen	Gelderland	6500HB	Netherlands

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
18794722	Derived	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.