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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Andrew Redington, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01164618
First received: July 14, 2010
Last updated: August 14, 2013
Last verified: August 2013

July 14, 2010
August 14, 2013
May 2010
February 2013   (final data collection date for primary outcome measure)
  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 1 of the Excercise intervention ] [ Designated as safety issue: No ]

    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.

  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 1 of the RIPC intervention ] [ Designated as safety issue: No ]

    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.

  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 2 of the Excercise intervention ] [ Designated as safety issue: No ]

    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.

  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 2 of the RIPC intervention ] [ Designated as safety issue: No ]

    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.

  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 10 of the Excercise intervention ] [ Designated as safety issue: No ]

    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.

  • Ischemia-reperfusion injury tolerance [ Time Frame: Day 10 of the RIPC intervention ] [ Designated as safety issue: No ]

    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.

Same as current
Complete list of historical versions of study NCT01164618 on ClinicalTrials.gov Archive Site
  • Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups [ Time Frame: Days 1, 2 and 10 days of each intervention (RIPC and Excercise) ] [ Designated as safety issue: No ]
  • Neutrophil Function - adhesion, phagocytotic index, and superoxide production over time within groups and between groups [ Time Frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise) ] [ Designated as safety issue: No ]
  • Neutrophil Gene Expression over time within groups and between groups [ Time Frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise) ] [ Designated as safety issue: No ]
  • Ischemia-reperfusion injury tolerance [ Time Frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise) ] [ Designated as safety issue: No ]
    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.
  • Exercise Capacity (VO2max) over time within groups and between groups [ Time Frame: Day 10 of each intervention (RIPC and Exercise) ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Ischemic Preconditioning
  • 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.
  • Experimental: Group 1
    The subjects in this arm will begin on the daily remote ischemic preconditioning (RIPC) protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily exercise.
    Interventions:
    • Procedure: Remote ischemic preconditioning (RIPC)
    • Other: Exercise
  • Experimental: Group 2
    The subjects in this arm will begin on the exercise protocol for 10 days. After a 21 day washout period they will then crossover to 10 days of daily remote ischemic preconditioning (RIPC).
    Interventions:
    • Procedure: Remote ischemic preconditioning (RIPC)
    • Other: Exercise
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
January 2014
February 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01164618
1000015862
No
Andrew Redington, The Hospital for Sick Children
The Hospital for Sick Children
Not Provided
Principal Investigator: Andrew Redington, MD The Hospital for Sick Children, Toronto Canada
The Hospital for Sick Children
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP