Ischemic PreconditioningPhase 2NCT01164618
The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
A Phase 2 study testing Remote ischemic preconditioning (RIPC) and Exercise in people with Ischemic Preconditioning, run by The Hospital for Sick Children at 1 site in Canada.
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 Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ischemic Preconditioning
- What is being tested?
- Remote ischemic preconditioning (RIPC) and Exercise
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- May 2010to Jan 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years,
- Informed consent
Who cannot join
- Contraindication to exercise,
- 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,
- 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,
- Alcohol and/or caffeine consumption in the 10 days prior to, or at any time during the study period
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Ischemic Preconditioning
- Being tested
- Remote ischemic preconditioning (RIPC), Exercise
- Keywords
- pediatrics, Remote ischemic preconditioning
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic preconditioning (RIPC)Procedure or surgery
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.
ExerciseOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 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. Receives: Procedure: Remote ischemic preconditioning (RIPC); Other: Exercise |
| Group 2 | Experimental | 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). Receives: Procedure: Remote ischemic preconditioning (RIPC); Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 of the Excercise intervention
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.
Measured: Day 1 of the RIPC intervention
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.
Measured: Day 2 of the Excercise intervention
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.
Measured: Day 2 of the RIPC intervention
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.
Measured: Day 10 of the Excercise intervention
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.
Measured: Day 10 of the RIPC intervention
Secondary outcomes (5)
Change in skeletal muscle metabolic parameters metabolism as measured by 31P-MRS and BOLD fMRI over time within groups and between groups
Measured: Days 1, 2 and 10 days of each intervention (RIPC and Excercise)
Neutrophil Function - adhesion, phagocytotic index, and superoxide production over time within groups and between groups
Measured: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Neutrophil Gene Expression over time within groups and between groups
Measured: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
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.
Measured: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Exercise Capacity (VO2max) over time within groups and between groups
Measured: Day 10 of each intervention (RIPC and Exercise)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2010 (estimated)
- Study startMay 2010
- Primary completionFeb 2013
- Study completionJan 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic PreconditioningStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Redington, The Hospital for Sick Children
- Investigators
- Andrew Redington, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01164618
- Sponsor's protocol ID
- 1000015862
- Status last verified
- Aug 2013
- First submitted
- 14 Jul 2010
- Last updated
- 15 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Biology of Chronic Preconditioning: Genomic and Physiologic Mechanisms of Response
- ClinicalTrials.gov ID
- NCT01164618
- Acronym / sponsor ID
- 1000015862
- Conditions
- Ischemic Preconditioning
- Keywords
- pediatrics, Remote ischemic preconditioning
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jan 2014 (estimated)
- First posted
- 16 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Procedure: Remote ischemic preconditioning (RIPC), Other: ExerciseThe 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. |
| Group 2 | Experimental | Procedure: Remote ischemic preconditioning (RIPC), Other: ExerciseThe 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years,
- Informed consent
Key exclusion criteria (5 listed)
- Contraindication to exercise,
- 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,
- 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,
- Alcohol and/or caffeine consumption in the 10 days prior to, or at any time during the study period
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Procedure or surgery | Group 1, Group 2 |
| ExerciseSubjects 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. | Other | Group 1, Group 2 |
Primary outcome
Ischemia-reperfusion injury tolerance
Time frame: Day 1 of the Excercise intervention
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
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
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
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
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
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.
5 secondary outcomes
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)
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)
Neutrophil Gene Expression over time within groups and between groups
Time frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Ischemia-reperfusion injury tolerance
Time frame: Days 1, 2 and 10 of each intervention (RIPC and Excercise)
Exercise Capacity (VO2max) over time within groups and between groups
Time frame: Day 10 of each intervention (RIPC and Exercise)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2013.
Related trials for Ischemic Preconditioning
Recruiting
Efficacy and Safety of Ischemic Preconditioning Therapy Versus Optimal Medical Therapy in Reducing the Recurrence of Ischemic Events in Symptomatic Moyamoya Disease
Moya Moya Disease, Moyamoya Syndrome
Recruiting
Effects of Remote Ischemic Preconditioning at Different Time Phases in Patients Undergoing Heart Valve Surgery
Heart Valve Surgery, Acute Kidney Injury
Recruiting
Effectiveness of Remote Ischemic Preconditioning for Prevention of Contrast Induced Acute Kidney Injury in Patients Undergoing Coronary Angiograms.
Contrast-induced Acute Kidney Injury (CI-AKI) Following Coronary Angiogram (CI-AKI), Contrast-induced Nephropathy Following Coronary Angiogram (CIN)
Recruiting
Remote Ischemic Preconditioning for Aute Type A Aortic Dissection Surgery
Aortic Dissection Type A
Not yet recruiting
Prevention of Ischemia in Aneurysmal Subarachnoid Hemorrhage Through Remote Ischemic Preconditioning
Aneurysmal Subarachnoid Hemorrhage
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Redington, MD principal investigator
The Hospital for Sick Children, Toronto Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Remote ischemic preconditioning (RIPC) and Exercise in people with Ischemic Preconditioning, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ischemia-reperfusion injury tolerance (time frame: Day 1 of the Excercise intervention). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2013.