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Clinical Trials/NCT00791206
NCT00791206UnknownPhase 2

Single Blind Randomized Controlled Crossover Trial of the Effects of Remote Preconditioning on the Tissue Metabolism During Exercise and Ischemia

The Hospital for Sick Children0 sites20 target enrollmentStarted: November 1, 2008Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Phase 2
Enrollment
20
Primary Endpoint
Improvement of endothelial and microvascular dysfunction induced by 20 minutes of forearm ischemia.

Study Overview

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 Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Masking
Single (Participant)

Eligibility Criteria

Ages
16 Years to 40 Years (Child, Adult)
Sex
All
Accepts Healthy Volunteers
Yes

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)

Arms & Interventions

2

Other

Intervention: Sham preconditioning (Procedure)

1

Experimental

Intervention: Real preconditioning (Procedure)

Outcomes

Primary Outcomes

Improvement of endothelial and microvascular dysfunction induced by 20 minutes of forearm ischemia.

Time Frame: 1 hour

Improvement in mitochondrial function following the preconditioning as evidenced by a faster rate of recovery of phosphocreatinine after exercise.

Time Frame: 2 hours

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Andrew Redington

Head, Heart Centre-Cardiology Division

The Hospital for Sick Children

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