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Sponsors and Collaborators: |
Radboud University ZonMw: The Netherlands Organisation for Health Research and Development |
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Information provided by: | Radboud University |
ClinicalTrials.gov Identifier: | NCT00319059 |
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 |
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AMPD Ischemic Tolerance |
Drug: systemic administration of 99mTc-HYNIC-Annexin A5 Behavioral: 10 minutes of ischemic handgripping |
Study Type: | Interventional |
Study Design: | Diagnostic, Non-Randomized, Single Blind, Placebo Control, Parallel Assignment, Pharmacodynamics Study |
Official Title: | The Influence of the 34C>T Variant in the AMPD1 Gene on Individual Susceptibility for Ischemia-Reperfusion. |
Ages Eligible for Study: | 18 Years to 40 Years |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Study ID Numbers: | AMPD-Annexin |
Study First Received: | April 27, 2006 |
Last Updated: | October 12, 2006 |
ClinicalTrials.gov Identifier: | NCT00319059 History of Changes |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Disease Susceptibility Annexin A5 Genetic Predisposition to Disease Ischemia |
Pathologic Processes Ischemia |