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
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
More Related Trials
-
Examining Genetic Influence on Response to Beta-Blocker Medications in People With Type 2 Diabetes
NCT00925119 ·Status: TERMINATED ·Phase: PHASE4
-
Clinical Outcome and Cost-effectiveness of Reduced Noradrenaline by Using a Lower Blood Pressure Target in Patients With Cardiogenic Shock From Acute Myocardial Infarction
NCT05168462 ·Status: RECRUITING ·Phase: PHASE4
-
Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
NCT01798992 ·Status: COMPLETED ·Phase: PHASE4
-
Sympathetic and Vascular Function in Takotsubo Syndrome
NCT05768542 ·Status: COMPLETED ·Phase: PHASE1/PHASE2
-
Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial.
NCT01311700 ·Status: COMPLETED ·Phase: PHASE4
-
Real-life Experience of the Use of Isomers as METPURE XL (S (-) Metoprolol Succinate) for Evaluation of Efficacy, Safety and Tolerability in the Management of Cardiovascular Disease in Colombian Patients
NCT01426594 ·Status: UNKNOWN
-
Transplanted-like Heart in Critical Ill Patients
NCT01930669 ·Status: COMPLETED ·Phase: NA
-
Use of Beta Blockers in Elderly Trauma Patients
NCT00302692 ·Status: UNKNOWN ·Phase: PHASE2
-
Leptin Infusion and Endothelial Vasomotor Response
NCT04374500 ·Status: COMPLETED ·Phase: EARLY_PHASE1
-
Role of Sympathetic Overactivity and Angiotensin II in PTSD and CV
NCT02560805 ·Status: RECRUITING ·Phase: PHASE2
-
Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial
NCT00401882 ·Status: TERMINATED ·Phase: PHASE2
-
Adenosine Activity in Producing Venoarteriolar Reflexes
NCT01280071 ·Status: UNKNOWN ·Phase: NA
-
Pathophysiology of Cardiometabolic Risk Factors in African Americans
NCT01122407 ·Status: COMPLETED ·Phase: PHASE1
-
Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation
NCT01157572 ·Status: COMPLETED ·Phase: PHASE4
-
The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03532802 ·Status: COMPLETED ·Phase: PHASE2
-
Effect of BMS-914392 on Pharmacokinetics of Metoprolol
NCT01211821 ·Status: COMPLETED ·Phase: PHASE1
-
The Role of Nitrite in Preconditioning Mediated Tolerance to Ischemic Stress
NCT00250185 ·Status: COMPLETED ·Phase: PHASE1
-
Daily Stress and Vascular Function in Midlife as a Risk Factor for Cognitive Decline
NCT06466655 ·Status: COMPLETED ·Phase: NA
-
Nesiritide Therapy to Preserve Function of the Left Ventricle After Myocardial Infarction
NCT00573144 ·Status: COMPLETED ·Phase: PHASE2
-
Renal Denervation in Patients After Acute Coronary Syndrome
NCT01901549 ·Status: UNKNOWN ·Phase: PHASE2
-
Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol
NCT01404767 ·Status: TERMINATED ·Phase: PHASE4
-
Effect of Beta Blocker Treatment on Endothelial Function in Patients With Type 2 Diabetes or Chronic Heart Failure
NCT00497003 ·Status: COMPLETED ·Phase: PHASE4
-
Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT04133532 ·Status: COMPLETED ·Phase: PHASE4
-
Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT00588965 ·Status: COMPLETED ·Phase: NA
-
Sex-related Differences in Sympathetic Vascular Transduction in the Setting of Hypoxemia
NCT05256069 ·Status: COMPLETED ·Phase: EARLY_PHASE1