The Influence of the 34C>T Variant in the AMPD1 Gene Ischemic Tolerance

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2006 by Radboud University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00319059
First received: April 27, 2006
Last updated: October 12, 2006
Last verified: April 2006
  Purpose

Previous epidemiological studies have shown that in cardiovascular patients, the 34C>T variant in the gene encoding for the enzyme Adenosine Mono Phosphate Deaminase (AMPD1) is associated with prolonged survival.

The 34 C>T variant encodes a severely truncated, metabolically inactive protein. We hypothesize that during ischemia, in these patients AMP in preferentially converted into adenosine instead of IMP. Adenosine receptor stimulation, in turn, will increase resistance to ischemia-reperfusion in the myocardial tissue.

To test this hypothesis, 7 male healthy volunteers heterozygous for the 34C>T variant will be selected from 100 healthy volunteers, which we have previously genotyped. These subjects will be compared with 7 matched control subjects. Individual ischemic tolerance will be assessed in the thenar muscle using 99mTc-Annexin A5 scintigraphy.

Briefly, the circulation of the nondominant forearm will be interrupted for 10 minutes by inflation of an upperarm cuff to 200mmHg en concomitantly, the subjects will perform isometric rhythmic handgripping until exhaustion. Immediately upon reperfusion, 400 MBq of 99mTc-Annexin A5 will be administered intravenously. Finally, 1 and 4 hours post-injection, scintigrapghi imaging of both hand will be performed. Targeting of annexin A5 will be expressed as percentage difference between the experimental and control hand.


Condition Intervention
AMPD
Ischemic Tolerance
Drug: systemic administration of 99mTc-HYNIC-Annexin A5
Behavioral: 10 minutes of ischemic handgripping

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Diagnostic
Official Title: The Influence of the 34C>T Variant in the AMPD1 Gene on Individual Susceptibility for Ischemia-Reperfusion.

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 99mTc-Annexin A5 targeting

Estimated Enrollment: 14
Study Start Date: March 2006
Estimated Study Completion Date: April 2006
  Eligibility

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

Inclusion Criteria:

  • male
  • 18-40 years
  • healthy
  • AMPD1 34C>T variant (heterozygous) or matched control

Exclusion Criteria:

  • cardiovascular / pulmonary disease
  • diabetes / hypertension
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00319059

Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Gerard Rongen, MD, PhD Radboud University
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00319059     History of Changes
Other Study ID Numbers: AMPD-Annexin
Study First Received: April 27, 2006
Last Updated: October 12, 2006
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Ischemia
Pathologic Processes
Annexin A5
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014