<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03006731</url>
  </required_header>
  <id_info>
    <org_study_id>16-5760-DE</org_study_id>
    <nct_id>NCT03006731</nct_id>
  </id_info>
  <brief_title>High Intensity Interval Training for People With Stroke Deficits</brief_title>
  <acronym>HIIT-Stroke</acronym>
  <official_title>High Intensity Interval Training for People With Stroke Deficits: Optimizing the Exercise Intervention (The HIIT-Stroke Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the effects of an exercise training strategy called&#xD;
      high-intensity interval training (HIIT) to moderate intensity continuous exercise (MICE), on&#xD;
      walking function and cardiovascular fitness in stroke patients. Hypothesis: HIIT will result&#xD;
      in significantly greater benefit to fitness and mobility than MICE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using a randomized design, the study will evaluate the effects of 3 HIT sessions combined&#xD;
      with 2 MICE sessions per week on cardiovascular fitness and mobility compared to MICE&#xD;
      training 5 days/week. Participants post-stroke will be randomly assigned to either MICE (5&#xD;
      days per week (d∙wk-1)) or combined HIIT (3 d∙wk-1) with MICE (2 d∙wk-1). Both groups will be&#xD;
      exercising 5 times per week (walking on a treadmill with harness for fall protection); 3&#xD;
      times at the centre and 2 times at home. Outcome measures will be conducted before and after&#xD;
      24 weeks of training.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Only the outcome assessor is blinded for the cardiopulmonary exercise stress test but not for the 6-minute walk test.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Cardiovascular fitness - Peak oxygen uptake (VO2peak)</measure>
    <time_frame>0, 24 weeks</time_frame>
    <description>A symptom-limited exercise test will be performed on a treadmill with a harness for fall protection using a ramp protocol. Breath-by-breath gas samples will be collected via calibrated metabolic cart to determine peak oxygen uptake.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Six Minute Walk Test</measure>
    <time_frame>0, 24 weeks</time_frame>
    <description>This test measures the distance that an individual can quickly walk in a period of 6 minutes on a flat surface. Participants will complete one trial with the gait aide prescribed to them. The distance will be recorded. Participants can stop and rest or discontinue to the test at any time.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological Test Battery (change over time)</measure>
    <time_frame>0, 24 weeks</time_frame>
    <description>Two executive function measures to measure selective attention and executive inhibition processes as well as a measure to assess speed of processing will be used. We will also include Trails A and B, DKEFS verbal fluency, the Weschsler digit symbol coding assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VO2 during HIT and MICE</measure>
    <time_frame>9 weeks and 24 weeks</time_frame>
    <description>To determine the ability of patients to reach critical intensity thresholds during HIT training and MICE and to examine dose-response associations, the acute effects (time spent above the critical intensity levels) will be measured using an ambulatory oxygen monitor. Ventilatory values will be measured using the CORTEX Biophysik MetaMax®3X portable gas analyzer recorded every 10 seconds for calculation of the time spent above the critical levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Dual task gait velocity</measure>
    <time_frame>0, 24 weeks</time_frame>
    <description>This assessment will include four 10 metre walking tasks at maximal comfortable speed. Three minutes after the first two 10 metre trials, participants will be asked to repeat the walk with simultaneous serial 3 subtractions and then naming as many words as possible that begin with a certain letter of the alphabet [FAS]. The number of errors and time to complete the tasks will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence</measure>
    <time_frame>0 to 24 weeks</time_frame>
    <description>Attendance and completion of home-based sessions measured via exercise diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>0 to 24 weeks</time_frame>
    <description>Any adverse event or near miss is required to be reported as standard of care at Toronto Rehab/UHN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>24 weeks</time_frame>
    <description>questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Brain Blood Flow response to exercise</measure>
    <time_frame>9 weeks and 24 weeks</time_frame>
    <description>Transcarnial Doppler ultrasound of the MCA and simultaneous finger cuff blood pressure monitoring during exercise</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle Oxygenation</measure>
    <time_frame>0, 8 weeks, 12 weeks, 24 weeks</time_frame>
    <description>Near Infrared Spectroscopy (NIRS) measurement of the vastus lateralis during rest and exercise.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>High Intensity Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High Intensity Interval Training patients will attend the centre 3 times/week for 24 weeks. All subjects will participate in MICE aerobic training 5 days/week in the first four weeks of the study to provide a foundation of fitness and endurance for the safe prescription of HIIT. Subsequently, the HIIT group will replace 3 MICE training days with 3 HIIT. HIIT sessions will include two 20 minute protocols; 30:60 second work:active rest ratio, and 120:180 second work:active rest ratio on a treadmill with a harness for fall protection. In addition to supervised exercise training (3 times/week), MICE will be conducted 2 times/week in the home/community, which has been shown to be both safe and effective</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate Intensity Exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Moderate Intensity Continuous Exercise patients will attend the centre 3 times/week for 24 weeks. Participants will be progressed to 30 to 60 minutes of continuous exercise at the heart rate that occurred at the anaerobic threshold on the exercise test. Participants will exercise on a treadmill with a harness ofr fall protection. In addition to supervised exercise training (3 times/week), MICE will be conducted 2 times/week in the home/community by both cohorts.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>High Intensity Interval Training</intervention_name>
    <description>Supervised HIIT sessions will be conducted on a treadmill at Toronto Rehab's Cardiac Rehabilitation and Secondary Prevention Program. During each of the three supervised HIIT sessions each week, subjects will be prescribed 2 protocols with a combination of short to moderate duration exercise of near maximal intensity alternating longer periods of active recovery. The total duration for each HIT session will be approximately 20 minutes with an additional 5 minutes warm-up and cool down period.</description>
    <arm_group_label>High Intensity Training</arm_group_label>
    <other_name>HIIT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Moderate Intensity Continuous Exercise</intervention_name>
    <description>MICE sessions represent the standard of care exercise prescription at TRI. Participants will be instructed to complete 20-60 minutes of continuous aerobic exercise at or around the ventilatory anaerobic threshold achieved on the cardiopulmonary exercise test.</description>
    <arm_group_label>Moderate Intensity Exercise</arm_group_label>
    <other_name>MICE</other_name>
    <other_name>Standard</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  clinical diagnosis of stroke (hemorrhagic or ischemic),&#xD;
&#xD;
          -  ability to walk at least 100 m independently with or without an assistive device with&#xD;
             no severe limitations due to pain,&#xD;
&#xD;
          -  living in the community at least 10 weeks post stroke (no upper limit) with a&#xD;
             stroke-related motor impairment score of &lt;7 on the Chedoke-McMaster Stroke Assessment&#xD;
             scale of the leg or foot or with hemiparetic gait pattern,&#xD;
&#xD;
          -  no severe communicative aphasia or comprehensive aphasia as noted in in clinical&#xD;
             reports or referral form&#xD;
&#xD;
          -  no orthopedic issues that may be aggravated by HIT&#xD;
&#xD;
          -  ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  severe uncontrolled hypertension or orthostatic blood pressure decrease of &gt;20 mmHg&#xD;
&#xD;
          -  other cardiovascular morbidities which would limit exercise tolerance (e.g. horizontal&#xD;
             or downsloping ST-segment depression &gt;2 mm, symptomatic aortic stenosis, complex&#xD;
             arrhythmias),&#xD;
&#xD;
          -  unstable angina,&#xD;
&#xD;
          -  severe proliferative retinopathy or uncontrolled blood glucose,&#xD;
&#xD;
          -  hypertrophic cardiomyopathy&#xD;
&#xD;
          -  lower extremity claudication&#xD;
&#xD;
          -  cognitive and/or behavioral issues limiting participation in exercise testing and&#xD;
             training, prior unrelated neurological disorders or psychiatric illness&#xD;
&#xD;
          -  abdominal or inguinal hernia causing discomfort with routine activities.&#xD;
&#xD;
        Other issues will be considered case-by-case.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Marzolini, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toronto Rehabilitaiton Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paul Oh, MD</last_name>
    <role>Study Director</role>
    <affiliation>Toronto Rehabilitation Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toronto Rehabilitation Institute - Rumsey Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 2V6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
    <investigator_full_name>Susan Marzolini</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03006731
org study id: 16-5760-DE
nct id: NCT03006731
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to compare the effects of an exercise training strategy called
      high-intensity interval training (HIIT) to moderate intensity continuous exercise (MICE), on
      walking function and cardiovascular fitness in stroke patients. Hypothesis: HIIT will result
      in significantly greater benefit to fitness and mobility than MICE.
Using a randomized design, the study will evaluate the effects of 3 HIT sessions combined
      with 2 MICE sessions per week on cardiovascular fitness and mobility compared to MICE
      training 5 days/week. Participants post-stroke will be randomly assigned to either MICE (5
      days per week (d∙wk-1)) or combined HIIT (3 d∙wk-1) with MICE (2 d∙wk-1). Both groups will be
      exercising 5 times per week (walking on a treadmill with harness for fall protection); 3
      times at the centre and 2 times at home. Outcome measures will be conducted before and after
      24 weeks of training.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Only the outcome assessor is blinded for the cardiopulmonary exercise stress test but not for the 6-minute walk test.
measure: Change in Cardiovascular fitness - Peak oxygen uptake (VO2peak)
time frame: 0, 24 weeks
description: A symptom-limited exercise test will be performed on a treadmill with a harness for fall protection using a ramp protocol. Breath-by-breath gas samples will be collected via calibrated metabolic cart to determine peak oxygen uptake.
measure: Change in Six Minute Walk Test
time frame: 0, 24 weeks
description: This test measures the distance that an individual can quickly walk in a period of 6 minutes on a flat surface. Participants will complete one trial with the gait aide prescribed to them. The distance will be recorded. Participants can stop and rest or discontinue to the test at any time.
measure: Neuropsychological Test Battery (change over time)
time frame: 0, 24 weeks
description: Two executive function measures to measure selective attention and executive inhibition processes as well as a measure to assess speed of processing will be used. We will also include Trails A and B, DKEFS verbal fluency, the Weschsler digit symbol coding assessment.
measure: VO2 during HIT and MICE
time frame: 9 weeks and 24 weeks
description: To determine the ability of patients to reach critical intensity thresholds during HIT training and MICE and to examine dose-response associations, the acute effects (time spent above the critical intensity levels) will be measured using an ambulatory oxygen monitor. Ventilatory values will be measured using the CORTEX Biophysik MetaMax®3X portable gas analyzer recorded every 10 seconds for calculation of the time spent above the critical levels.
measure: Change in Dual task gait velocity
time frame: 0, 24 weeks
description: This assessment will include four 10 metre walking tasks at maximal comfortable speed. Three minutes after the first two 10 metre trials, participants will be asked to repeat the walk with simultaneous serial 3 subtractions and then naming as many words as possible that begin with a certain letter of the alphabet [FAS]. The number of errors and time to complete the tasks will be recorded.
measure: Adherence
time frame: 0 to 24 weeks
description: Attendance and completion of home-based sessions measured via exercise diary
measure: Adverse Events
time frame: 0 to 24 weeks
description: Any adverse event or near miss is required to be reported as standard of care at Toronto Rehab/UHN.
measure: Patient satisfaction
time frame: 24 weeks
description: questionnaire
measure: Change in Brain Blood Flow response to exercise
time frame: 9 weeks and 24 weeks
description: Transcarnial Doppler ultrasound of the MCA and simultaneous finger cuff blood pressure monitoring during exercise
measure: Muscle Oxygenation
time frame: 0, 8 weeks, 12 weeks, 24 weeks
description: Near Infrared Spectroscopy (NIRS) measurement of the vastus lateralis during rest and exercise.
arm group label: High Intensity Training
arm group type: Experimental
description: High Intensity Interval Training patients will attend the centre 3 times/week for 24 weeks. All subjects will participate in MICE aerobic training 5 days/week in the first four weeks of the study to provide a foundation of fitness and endurance for the safe prescription of HIIT. Subsequently, the HIIT group will replace 3 MICE training days with 3 HIIT. HIIT sessions will include two 20 minute protocols; 30:60 second work:active rest ratio, and 120:180 second work:active rest ratio on a treadmill with a harness for fall protection. In addition to supervised exercise training (3 times/week), MICE will be conducted 2 times/week in the home/community, which has been shown to be both safe and effective
arm group label: Moderate Intensity Exercise
arm group type: Active Comparator
description: Moderate Intensity Continuous Exercise patients will attend the centre 3 times/week for 24 weeks. Participants will be progressed to 30 to 60 minutes of continuous exercise at the heart rate that occurred at the anaerobic threshold on the exercise test. Participants will exercise on a treadmill with a harness ofr fall protection. In addition to supervised exercise training (3 times/week), MICE will be conducted 2 times/week in the home/community by both cohorts.
intervention type: Behavioral
intervention name: High Intensity Interval Training
description: Supervised HIIT sessions will be conducted on a treadmill at Toronto Rehab's Cardiac Rehabilitation and Secondary Prevention Program. During each of the three supervised HIIT sessions each week, subjects will be prescribed 2 protocols with a combination of short to moderate duration exercise of near maximal intensity alternating longer periods of active recovery. The total duration for each HIT session will be approximately 20 minutes with an additional 5 minutes warm-up and cool down period.
arm group label: High Intensity Training
other name: HIIT
intervention type: Behavioral
intervention name: Moderate Intensity Continuous Exercise
description: MICE sessions represent the standard of care exercise prescription at TRI. Participants will be instructed to complete 20-60 minutes of continuous aerobic exercise at or around the ventilatory anaerobic threshold achieved on the cardiopulmonary exercise test.
arm group label: Moderate Intensity Exercise
other name: MICE
other name: Standard
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Susan Marzolini, PhD
role: Principal Investigator
affiliation: Toronto Rehabilitaiton Institute
last name: Paul Oh, MD
role: Study Director
affiliation: Toronto Rehabilitation Institute
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University Health Network, Toronto
investigator full name: Susan Marzolini
investigator title: Principle Investigator
mesh term: Stroke
sharing ipd: No