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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00319059
Recruitment Status : Completed
First Posted : April 27, 2006
Last Update Posted : April 22, 2016
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Radboud University

Brief Summary:

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 or disease Intervention/treatment Phase
AMPD Ischemic Tolerance Drug: systemic administration of 99mTc-HYNIC-Annexin A5 Behavioral: 10 minutes of ischemic handgripping Not Applicable

Study Type : Interventional  (Clinical Trial)
Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single
Primary Purpose: Diagnostic
Official Title: The Influence of the 34C>T Variant in the AMPD1 Gene on Individual Susceptibility for Ischemia-reperfusion.
Study Start Date : March 2006
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. 99mTc-Annexin A5 targeting

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

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

Exclusion Criteria:

  • cardiovascular / pulmonary disease
  • diabetes / hypertension

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00319059

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

Responsible Party: Radboud University Identifier: NCT00319059     History of Changes
Other Study ID Numbers: AMPD-Annexin
First Posted: April 27, 2006    Key Record Dates
Last Update Posted: April 22, 2016
Last Verified: April 2016

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