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

NCT ID: NCT00791206

Last Updated: 2013-12-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-06-30

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.

Conditions

Ischemia

Keywords

exercise; ischemia; MRI; MRI spectroscopy; Ischemia preconditioning

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: SINGLE

Study Groups

1

Group Type: EXPERIMENTAL

Real preconditioning

Intervention Type: PROCEDURE

Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 15 mmHg greater than systolic arterial pressure.

2

Group Type: OTHER

Sham preconditioning

Intervention Type: PROCEDURE

Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 10mmHg with the same cycling protocol as the real preconditioning.

Interventions

Real preconditioning

Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 15 mmHg greater than systolic arterial pressure.

Intervention Type: PROCEDURE

Sham preconditioning

Preconditioning will consist of four 5 minutes cycles of upper limb ischemia interspaced with 5 minutes of reperfusion, using a blood-pressure cuff inflated to a pressure 10mmHg with the same cycling protocol as the real preconditioning.

Intervention Type: PROCEDURE

Eligibility Criteria

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)

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Andrew Redington

Head, Heart Centre-Cardiology Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew Redington, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Other Identifiers

1000012859

Identifier Type: -

Identifier Source: org_study_id