The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response

Ischemic Preconditioning Clinical Trial

Official title:

The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01164618
• Other study ID #: 1000015862
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 14, 2010
• Last updated: August 14, 2013
• Start date: May 2010
• Est. completion date: January 2014

Study information

• Verified date: August 2013
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the effects of repeated RIPC and exercise, on exercise performance, skeletal muscle responses and circulating cellular and humoral biology in humans

Description:

Remote ischemic preconditioning (RIPC) results in a powerful and widespread protective effect against subsequent prolonged ischemia-reperfusion (IR) injury of distant organs and systemic inflammatory responses, both of which are key elements in the evolution of local and multiorgan effects of many clinical IR syndromes. The signal transduction within the target organ to generate ischemia tolerance, and the effects of RIPC on systemic anti-inflammatory pathways, however, remain to be elucidated fully. Particularly, data regarding the mechanisms of 'second window' protection (a resurgence of protection 24-72 hrs after the initial RIPC stimulus) is scant; even less is known of the effects of repeated RIPC, and a potential 'third window' of protection. Our preliminary data and several recent publications have shown that the biology of RIPC and exercise show considerable overlap. This research has raised the possibility of a reciprocal effect between RIPC and exercise, with chronic exercise being a model of the potential effects of 'chronic preconditioning'. This is relevant, as repeated RIPC might be a strategy to improve exercise function in those with limited exercise tolerance e.g. heart failure.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: January 2014
• Est. primary completion date: February 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years,

2. Informed consent

Exclusion Criteria:

1. Contraindication to exercise,

2. Vigorous aerobic/anaerobic exercise in duration of =15 minutes during the 21 days prior to commencement of the study, or either of the RIPC or exercise protocol arms,

3. Overt viral or bacterial infection in the 10 days prior to commencement of the study, or during either of the RIPC or exercise protocol arms,

4. Alcohol and/or caffeine consumption in the 10 days prior to, or at any time during the study period

5. Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Ischemic Preconditioning

Intervention

Procedure:
• Remote ischemic preconditioning (RIPC)
RIPC will be induced using a standard blood pressure cuff and hand anaeroid sphygmomanometer, on the right arm. The subject will be seated, the blood pressure cuff placed on the arm and inflated to a pressure of 200mmHg for 5 minutes (ischemia). The cuff will then be deflated for 5 minutes (reperfusion) completing one cycle of ischemia reperfusion. A total of 4 inflation and deflation cycles will be applied. This protocol of RIPC will be applied daily, for 10 consecutive days.

Other:
• Exercise
Subjects will then undergo exercise daily, for 10 consecutive days. A chronic high-intensity interval exercise training protocol standardized to subjects' aerobic power (VO¬2max) will be used. Each exercise session will consist of a 5 min warm-up period followed by 4 sets of 2 min high intensity intervals interspersed with 3 min recovery periods.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 1 of the Excercise intervention	No
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 1 of the RIPC intervention	No
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 2 of the Excercise intervention	No
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 2 of the RIPC intervention	No
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 10 of the Excercise intervention	No
Primary	Ischemia-reperfusion injury tolerance	This will be done to assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.; This measure will be compared over time within groups and between groups.	Day 10 of the RIPC intervention	No
Secondary	Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups		Days 1, 2 and 10 days of each intervention (RIPC and Excercise)	No
Secondary	Neutrophil Function - adhesion, phagocytotic index, and superoxide production over time within groups and between groups		Days 1, 2 and 10 of each intervention (RIPC and Excercise)	No
Secondary	Neutrophil Gene Expression over time within groups and between groups		Days 1, 2 and 10 of each intervention (RIPC and Excercise)	No
Secondary	Ischemia-reperfusion injury tolerance	We will assess whether chronic preconditioning in humans generates a circulating effector(s) responsible for the generation of cardioprotection in our mouse model of ischemia-reperfusion injury.	Days 1, 2 and 10 of each intervention (RIPC and Excercise)	No
Secondary	Exercise Capacity (VO2max) over time within groups and between groups		Day 10 of each intervention (RIPC and Exercise)	No