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

NCT ID: NCT00319059

Last Updated: 2016-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2006-04-30

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.

Conditions

AMPD; Ischemic Tolerance

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Interventions

systemic administration of 99mTc-HYNIC-Annexin A5

Intervention Type: DRUG

10 minutes of ischemic handgripping

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• cardiovascular / pulmonary disease
• diabetes / hypertension

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerard Rongen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Other Identifiers

AMPD-Annexin

Identifier Type: -

Identifier Source: org_study_id