Clinical trial NCT01164618: The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
Official title: The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemic Preconditioning
Keywords: pediatrics
Remote ischemic preconditioning
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2010-07-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 1 of the Excercise intervention
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 1 of the RIPC intervention
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 2 of the Excercise intervention
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 2 of the RIPC intervention
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 10 of the Excercise intervention
measure: Ischemia-reperfusion injury tolerance
timeFrame: Day 10 of the RIPC intervention
Secondary outcomes:
measure: Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups
timeFrame: Days 1, 2 and 10 days of each intervention (RIPC and Excercise)
measure: Neutrophil Function - adhesion, phagocytotic index, and superoxide production over time within groups and between groups
timeFrame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
measure: Neutrophil Gene Expression over time within groups and between groups
timeFrame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
measure: Ischemia-reperfusion injury tolerance
timeFrame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
measure: Exercise Capacity (VO2max) over time within groups and between groups
timeFrame: Day 10 of each intervention (RIPC and Exercise)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Andrew Redington, MD
role: PRINCIPAL_INVESTIGATOR
References: