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Biomarkers of Reaction To HIIT Exercise (BReaTHE)

Primary Purpose

Stroke, Stroke Rehabilitation, Lower Extremity Weakness, Spastic

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
High Intensity Interval Training (HIIT)
Sponsored by
Atlanta VA Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring Predictors of Stroke Rehabilitation, Biomarkers of Stroke Rehabilitation, Exercise Intervention, Neuroimaging

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: chronic left or right subcortical stroke as defined by 6 months or more after a cardiovascular accident lower extremity motor impairment due to stroke that causes a walking speed of less than 0.6 m/s during a 10m walk age 18-80 years old Veteran status. Exclusion Criteria: MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia any neurodegenerative condition other than stroke that may lead to lower extremity impairment a visual or auditory impairment that may hinder study procedures any medical condition that would preclude participation in a physical exercise intervention program.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Chronic Stroke with lower limb disability

    Arm Description

    The investigators will enroll 55 Veterans with chronic subcortical stroke in the 12-week HIIT intervention, with the expectation that 48 participants (85%) will complete the entire program. In our experience, 65% of participants will respond to the HIIT intervention, resulting in an estimated 31 responders and 17 resistors. Each chronic subcortical stroke participant will be asked to participate in the HIIT study protocol. Classification of resistor or responder: A responder to the 12-week HIIT intervention will be defined as a participant who increases their walking speed to greater than 0.6 m/s. A resistor to the intervention will be defined as a participant who does not increase their walking speed to greater than 0.6 m/s.

    Outcomes

    Primary Outcome Measures

    10 m walk test on a GAITRite mat
    To assess short-distance walking speed and gait characteristics.
    Timed-Up-and-Go (TUG) test
    To assess short-distance walking and postural control.
    6-minute walk test
    To assess endurance.

    Secondary Outcome Measures

    Blood lactate change during HIIT session
    To assess if the participant increases their blood lactate during the HIIT session.
    MEGA-PRESS Magnetic Resonance Spectroscopy
    To assess GABA from the ipsilesional and contralesional leg areas of the brain.
    pseudo Continuous Arterial Spin Labeling MRI
    To assess whole brain regional cerebral blood flow.
    Graded treadmill or bike testing
    To estimate VO2-max.

    Full Information

    First Posted
    September 18, 2023
    Last Updated
    September 22, 2023
    Sponsor
    Atlanta VA Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06059872
    Brief Title
    Biomarkers of Reaction To HIIT Exercise
    Acronym
    BReaTHE
    Official Title
    What Makes a Responder, a Responder? Biomarkers to Help Identify Responders and Resistors to High-intensity Interval Training for Lower Extremity Chronic Stroke
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2024 (Anticipated)
    Primary Completion Date
    June 2027 (Anticipated)
    Study Completion Date
    December 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Atlanta VA Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Stroke survivors with lower limb disability can improve their walking speed with high-intensity interval training (HIIT) rehabilitation therapy. However, some individuals may not respond to HIIT even when fully adherent to the program. To address this, the investigators propose to build a predictive model that identifies if a Veteran with chronic subcortical stroke will improve their walking speed with HIIT by incorporating blood lactate as an early predictor of exercise response, and inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and regional cerebral blood flow (CBF) as predictors of the brain's potential to respond, while also taking into consideration other factors such as comorbidities, demographics, and fitness levels.
    Detailed Description
    Most chronic subcortical stroke survivors have difficulty walking, but few predictors can help identify if a patient will respond to an exercise regimen and improve their function. To enhance precision rehabilitation for chronic subcortical stroke patients, personalized aerobic exercise interventions are crucial. This requires the development of innovative technologies that can identify the essential neurobiological factors to predict intervention response and enable clinicians to determine individualized rehabilitation targets. Lactate is one exciting new target that acts as a molecular messenger between the periphery and the brain. For lactate to have an impact on other organs, including the brain, there must be a substantial increase in its level in the bloodstream from baseline. When the blood lactate threshold is surpassed during exercise, lactate acts on the brain metabolically via the TCA cycle. Embedded within the TCA cycle is the means to increase or decrease neurotransmitter concentrations such as GABA and glutamate. Gamma-aminobutyric acid (GABA), the brain's major inhibitory neurotransmitter, is a new treatment target that promotes neural plasticity during stroke rehabilitation. Drawing from the framework of personalized rehabilitation approaches and our preliminary data, the investigators propose to build a predictive model that can identify if a chronic subcortical stroke patient will respond to exercise training. This model aims to predict improvements in walking speed by incorporating blood lactate as an early predictor of exercise response and GABA and cerebral blood flow (CBF) as predictors of the brain's potential to respond, in addition to other influencing factors such as comorbidities, demographics, and fitness levels. The overarching hypothesis is that robust neurophysiological factors driven by lactate can differentiate responders from resistors and that these factors can be applied clinically as biomarkers to predict functional outcomes after a 12-week HIIT intervention. The investigators will assess improvements in walking speed in 48 Veterans with lower limb disability due to chronic subcortical stroke in response to a 36-session (12-week) HIIT intervention. After the intervention, each adherent participant who improves their walking speed to greater than 0.6 m/s will be categorized as a responder while each adherent participant who does not improve their walking speed will be categorized as a resistor. At baseline and after 12 weeks of HIIT the investigators will evaluate walking speed, balance, leg strength, and endurance to identify resistors and responders to HIIT and collect a) GABA from the primary sensory-motor leg area using single-voxel magnetic resonance spectroscopy, b) CBF from the whole brain using pseudo-Continuous Arterial Spin Labeling MRI and c) VO2 max to evaluate change in CRF. During the intervention, the investigators will collect blood lactate via finger prick during sessions 1, 4, 7, 10, and 28 to assess its potential as an early predictor of exercise response. In aim 1 the investigators determine if surpassing the lactate threshold during the first 4 weeks of HIIT predicts the change in walking speed to ≥0.6 m/s, from pre- to post-HIIT. If lactate proves to be a robust early marker of functional response to exercise, the investigators will have an easy-to-deploy predictor of who will best benefit from HIIT. In aim 2 the investigators will determine if (a) baseline GABA and/or CBF predict improvements in walking speed from baseline to after HIIT and (b) if a change in GABA and/or CBF relate to a change in walking speed. The investigators aim to establish neurophysiological correlates of improving function with HIIT to better understand the mechanisms. Finally, in aim 3 the investigators will a predictive machine learning algorithm of who will improve their walking speed with HIIT using factors of blood lactate, baseline GABA and CBF, baseline leg weakness and VO2-max, pre-stroke fitness, age, sex, and comorbidities. The overarching objective is to develop a model to predict which Veteran with chronic stroke will respond to a 12-week exercise program.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stroke, Stroke Rehabilitation, Lower Extremity Weakness, Spastic, Walking, Difficulty
    Keywords
    Predictors of Stroke Rehabilitation, Biomarkers of Stroke Rehabilitation, Exercise Intervention, Neuroimaging

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Model Description
    The investigators will enroll 55 Veterans with chronic subcortical stroke in the 12-week HIIT intervention, with the expectation that 48 participants (85%) will complete the entire program. In our experience, 65% of participants will respond to the HIIT intervention, resulting in an estimated 31 responders and 17 resistors. Each chronic subcortical stroke participant will be asked to participate in the overall study protocol with pre-, during-, and post-intervention measurements. The HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at the Atlanta VA, administered by a trained exercise physiologist, for a total of 36 HIIT sessions.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    55 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Chronic Stroke with lower limb disability
    Arm Type
    Experimental
    Arm Description
    The investigators will enroll 55 Veterans with chronic subcortical stroke in the 12-week HIIT intervention, with the expectation that 48 participants (85%) will complete the entire program. In our experience, 65% of participants will respond to the HIIT intervention, resulting in an estimated 31 responders and 17 resistors. Each chronic subcortical stroke participant will be asked to participate in the HIIT study protocol. Classification of resistor or responder: A responder to the 12-week HIIT intervention will be defined as a participant who increases their walking speed to greater than 0.6 m/s. A resistor to the intervention will be defined as a participant who does not increase their walking speed to greater than 0.6 m/s.
    Intervention Type
    Other
    Intervention Name(s)
    High Intensity Interval Training (HIIT)
    Intervention Description
    HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at the Atlanta VA, administered by a trained exercise physiologist, for a total of 36 HIIT sessions.
    Primary Outcome Measure Information:
    Title
    10 m walk test on a GAITRite mat
    Description
    To assess short-distance walking speed and gait characteristics.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Title
    Timed-Up-and-Go (TUG) test
    Description
    To assess short-distance walking and postural control.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Title
    6-minute walk test
    Description
    To assess endurance.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Secondary Outcome Measure Information:
    Title
    Blood lactate change during HIIT session
    Description
    To assess if the participant increases their blood lactate during the HIIT session.
    Time Frame
    On exercise day 1, 4, 7, 10, and 28. The total number of exercise days is 36 (3 times per week for 12 weeks).
    Title
    MEGA-PRESS Magnetic Resonance Spectroscopy
    Description
    To assess GABA from the ipsilesional and contralesional leg areas of the brain.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Title
    pseudo Continuous Arterial Spin Labeling MRI
    Description
    To assess whole brain regional cerebral blood flow.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Title
    Graded treadmill or bike testing
    Description
    To estimate VO2-max.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Other Pre-specified Outcome Measures:
    Title
    Repetition max strength test
    Description
    To assess the leg strength of the affected and less affected leg.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)
    Title
    Global physical activity questionnaire (GPAQ)
    Description
    To assess pre-stroke fitness levels.
    Time Frame
    baseline (week 1)
    Title
    Self-administered Comorbidity Questionnaire (SCQ)
    Description
    To assess the presence and burden of comorbidities.
    Time Frame
    baseline (week 1) and after the completion of 12 weeks of exercise (week 14)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: chronic left or right subcortical stroke as defined by 6 months or more after a cardiovascular accident lower extremity motor impairment due to stroke that causes a walking speed of less than 0.6 m/s during a 10m walk age 18-80 years old Veteran status. Exclusion Criteria: MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia any neurodegenerative condition other than stroke that may lead to lower extremity impairment a visual or auditory impairment that may hinder study procedures any medical condition that would preclude participation in a physical exercise intervention program.

    12. IPD Sharing Statement

    Learn more about this trial

    Biomarkers of Reaction To HIIT Exercise

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