Trial of the Effects of Remote Preconditioning on the Tissue Metabolism During Exercise and Ischemia

Phase 2

• Conditions: Ischemia
• Interventions: Procedure: Real preconditioning; Procedure: Sham preconditioning

• Registration Number: NCT00791206
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Previously, the preconditioning signaling pathways have been studied on molecular level or in animal model. By using MR spectroscopy and imaging in a dynamic human model of preconditioning, we will have a better understanding how mitochondrial and endothelial function are affected by preconditioning in-vivo.

Detailed Description

Ischemic preconditioning is a mechanism that protects tissue against ischemia-reperfusion injury. The protective effect of preconditioning is induced by short periods (1-5 minutes) of non-lethal ischemia to the target tissue, which becomes resistant to a prolonged, otherwise lethal, period of ischemia. Despite its proven potency in experimental models, ischemic preconditioning has not reached widespread clinical application because of the difficulties in applying the stimulus to the target organ (eg Heart, Brain), and even brief ischemia to the target organ can cause dysfunction.

Remote ischemic preconditioning (RIPC) is a more clinically relevant stimulus. It has been shown that preconditioning of one coronary territory induces ischemia protection in other parts of the heart. Subsequently, other studies have shown, in rodent models, that preconditioning of one organ (eg kidney) could induce protection in other organs (eg heart). We recently have confirmed, in a series of animal and human preclinical studies, that this concept can be widened; ultimately showing that four 5-minute episodes of ischemia to the skeletal limb muscles (induced by inflating a standard blood pressure cuff to a level higher than the blood pressure) protects the heart and lungs against ischemia-reperfusion injury in children undergoing cardiac surgery using cardiopulmonary bypass.

The current research is designed to investigate with MRI spectroscopy techonology, the potential physiological mechanisms involved in the protective effects of preconditioning, and the effects of ischemia and exercise.

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2008-11-13
• Study First Submitted QC: 2008-11-13
• Study First Posted: 2008-11-14
• Primary Completion: 2013-06
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-13
• Last Update Posted: 2013-12-16
• Study Completion: 2014-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Healthy male and female volunteers
• Post-pubescent non-athletes between the ages of >16 and <40 years of age.

Exclusion Criteria

• Older than 40 year old.
• Younger than 16 year old.
• Major medical condition
• Illness, surgery or medical intervention in the last 48 hours.
• Diabetes Mellitus
• Caffeine intake in the last 48 hours
• Athlete (more than 5 training sessions per week)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	Real preconditioning	-
2	Sham preconditioning	-

Primary Outcome Measures

Name	Time	Method
Improvement of endothelial and microvascular dysfunction induced by 20 minutes of forearm ischemia.	1 hour
Improvement in mitochondrial function following the preconditioning as evidenced by a faster rate of recovery of phosphocreatinine after exercise.	2 hours