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

NCT00319059 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 14

Last updated 2016-04-22

No results posted yet for this study

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.

Conditions

  • AMPD
  • Ischemic Tolerance

Interventions

DRUG

systemic administration of 99mTc-HYNIC-Annexin A5

BEHAVIORAL

10 minutes of ischemic handgripping

Sponsors & Collaborators

  • ZonMw: The Netherlands Organisation for Health Research and Development

    collaborator OTHER
  • Radboud University Medical Center

    lead OTHER

Principal Investigators

  • Gerard Rongen, MD, PhD · Radboud University Medical Center

Study Design

Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
40 Years
Sex
MALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2006-03-31
Primary Completion
2006-04-30
Completion
2006-04-30

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Read the full study record

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View NCT00319059 on ClinicalTrials.gov