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

• ClinicalTrials.gov Identifier: NCT00791206
• Recruitment Status: Unknown
• First Posted: November 14, 2008
• Last Update Posted: December 16, 2013
• Sponsor: The Hospital for Sick Children
• Information provided by (Responsible Party): Andrew Redington, The Hospital for Sick Children

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ischemia	Procedure: Real preconditioning; Procedure: Sham preconditioning	Phase 2

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 (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Official Title: Single Blind Randomized Controlled Crossover Trial of the Effects of Remote Preconditioning on the Tissue Metabolism During Exercise and Ischemia
• Study Start Date: November 2008
• Actual Primary Completion Date: June 2013
• Estimated Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Procedure: 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.
2	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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 40 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Sponsors and Collaborators

The Hospital for Sick Children

Investigators

• Principal Investigator: Andrew Redington, MD; The Hospital for Sick Children

More Information

• Responsible Party: Andrew Redington, Head, Heart Centre-Cardiology Division, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT00791206
• Other Study ID Numbers: 1000012859
• First Posted: November 14, 2008
• Last Update Posted: December 16, 2013
• Last Verified: December 2013

Keywords provided by Andrew Redington, The Hospital for Sick Children:

exercise; ischemia; MRI; MRI spectroscopy; Ischemia preconditioning

Additional relevant MeSH terms:

Ischemia; Pathologic Processes