<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/NCT03760016</url>
  </required_header>
  <id_info>
    <org_study_id>2017-5325</org_study_id>
    <secondary_id>R01HD093694</secondary_id>
    <nct_id>NCT03760016</nct_id>
  </id_info>
  <brief_title>Moderate-Intensity Exercise Versus High-Intensity Interval Training to Recover Walking Post-Stroke</brief_title>
  <official_title>Moderate-Intensity Exercise Versus High-Intensity Interval Training to Recover Walking Post-Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Delaware</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Kansas Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</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 objective of this study is to determine the optimal training intensity and the minimum&#xD;
      training duration needed to maximize immediate improvements in walking capacity in chronic&#xD;
      stroke. A single-blind, phase II, 3-site randomized controlled trial has been planned. Fifty&#xD;
      persons &gt;6 months post stroke will randomize to either moderate-intensity aerobic locomotor&#xD;
      training or high-intensity interval locomotor training; each for 45 minutes, 3x/week for up&#xD;
      to 36 total sessions over approximately 12 weeks. Clinical measures of walking function,&#xD;
      aerobic fitness, daily walking activity and quality of life will be assessed at baseline&#xD;
      (PRE) and after 4, 8 and 12 weeks of training (POST-4WK, POST-8WK, POST-12WK).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 4, 2019</start_date>
  <completion_date type="Actual">April 25, 2022</completion_date>
  <primary_completion_date type="Actual">April 25, 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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Six-Minute Walk Test Distance</measure>
    <time_frame>Change Six-Minute Walk Test Distance from Baseline to 4 Weeks</time_frame>
    <description>Total distance walked in 6 minutes in meters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Six-Minute Walk Test Distance</measure>
    <time_frame>Change Six-Minute Walk Test Distance from Baseline to 8 Weeks</time_frame>
    <description>Total distance walked in 6 minutes in meters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Six-Minute Walk Test Distance</measure>
    <time_frame>Change Six-Minute Walk Test Distance from Baseline to 12 Weeks</time_frame>
    <description>Total distance walked in 6 minutes in meters</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comfortable Gait Speed</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>From 10-meter walk test, in meters per second</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fast Gait Speed</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>From 10-meter walk test, in meters per second</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aerobic Fitness</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS-Fatigue Scale</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>An 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total score will be calculated by averaging the scores for each item.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exercise Capacity</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>Time to exhaustion during treadmill graded exercise test, recorded in minutes</description>
  </other_outcome>
  <other_outcome>
    <measure>Peak Oxygen Consumption Rate</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute</description>
  </other_outcome>
  <other_outcome>
    <measure>Metabolic Cost of Gait</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter</description>
  </other_outcome>
  <other_outcome>
    <measure>EuroQol 5D-5L (EQ-5D-5L)</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>A 6-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, anxiety/depression and overall health. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total score will be calculated by averaging the scores for each item.</description>
  </other_outcome>
  <other_outcome>
    <measure>Activities-specific Balance Confidence Scale</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score will be calculated by averaging the scores for each item.</description>
  </other_outcome>
  <other_outcome>
    <measure>Daily Walking Activity</measure>
    <time_frame>4 ,8, 12 weeks</time_frame>
    <description>Mean daily step count recorded with activity monitor, recorded as steps per day</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Moderate-Intensity Aerobic Training</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High-Intensity Interval Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Moderate-Intensity Aerobic Training</intervention_name>
    <description>Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
    <arm_group_label>Moderate-Intensity Aerobic Training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>High-Intensity Interval Training</intervention_name>
    <description>Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
    <arm_group_label>High-Intensity Interval Training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 40-80 years at time of consenting&#xD;
&#xD;
          2. Single stroke for which participant sought treatment, 6 months to 5 years prior to&#xD;
             consent date&#xD;
&#xD;
          3. Walking speed &lt;1.0 m/s on the 10-meter walk test&#xD;
&#xD;
          4. Able to walk 10m over ground with assistive devices as needed and no continuous&#xD;
             physical assistance from another person (guarding and intermittent assistance for loss&#xD;
             of balance allowed)&#xD;
&#xD;
          5. Able to walk at least 3 minutes on the treadmill at ≥0.13m/s (0.3 mph)&#xD;
&#xD;
          6. Stable cardiovascular condition (AHA class B, allowing for aerobic capacity &lt;6&#xD;
             metabolic equivalents)&#xD;
&#xD;
          7. Able to communicate with investigators, follow a 2-step command and correctly answer&#xD;
             consent comprehension questions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Exercise testing uninterpretable for ischemia or arrhythmia (e.g. resting ECG&#xD;
             abnormality that makes exercise ECG uninterpretable for ischemia and no other clinical&#xD;
             testing from the past year available to rule out)&#xD;
&#xD;
          2. Evidence of significant arrhythmia or myocardial ischemia on treadmill ECG graded&#xD;
             exercise test in the absence of recent (past year) more definitive clinical testing&#xD;
             (e.g. stress nuclear imaging) with negative result&#xD;
&#xD;
          3. Hospitalization for cardiac or pulmonary disease within past 3 months&#xD;
&#xD;
          4. Implanted pacemaker or defibrillator&#xD;
&#xD;
          5. Significant ataxia or neglect (score of 2 on NIH stroke scale item 7 or 11)&#xD;
&#xD;
          6. Severe lower limb spasticity (Ashworth &gt;2)&#xD;
&#xD;
          7. Recent history (&lt;3 months) of illicit drug or alcohol abuse or significant mental&#xD;
             illness&#xD;
&#xD;
          8. Major post-stroke depression (Patient Health Questionnaire [PHQ-9] ≥ 10) in the&#xD;
             absence of depression management by a health care provider&#xD;
&#xD;
          9. Currently participating in physical therapy or another interventional study&#xD;
&#xD;
         10. Recent botulinum toxin injection to the paretic lower limb (&lt;3 months) or planning to&#xD;
             have lower limb botulinum toxin injection in the next 4 months&#xD;
&#xD;
         11. Foot drop or lower limb joint instability without adequate stabilizing device, as&#xD;
             assessed by a physical therapist&#xD;
&#xD;
         12. Clinically significant neurologic disorder other than stroke or unable to walk outside&#xD;
             the home prior to stroke&#xD;
&#xD;
         13. Other significant medical condition likely to limit improvement or jeopardize safety&#xD;
             as assessed by a physical therapist (e.g. joint contracture, gait limited by pain)&#xD;
&#xD;
         14. Pregnancy&#xD;
&#xD;
         15. Previous exposure to fast treadmill walking (&gt;3 cumulative hours) during clinical or&#xD;
             research therapy in the past year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierce Boyne, DPT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Delaware</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Boyne P, Billinger SA, Reisman DS, Awosika OO, Buckley S, Burson J, Carl D, DeLange M, Doren S, Earnest M, Gerson M, Henry M, Horning A, Khoury JC, Kissela BM, Laughlin A, McCartney K, McQuaid T, Miller A, Moores A, Palmer JA, Sucharew H, Thompson ED, Wagner E, Ward J, Wasik EP, Whitaker AA, Wright H, Dunning K. Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Apr 1;80(4):342-351. doi: 10.1001/jamaneurol.2023.0033.</citation>
    <PMID>36822187</PMID>
  </results_reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <results_first_submitted>July 13, 2023</results_first_submitted>
  <results_first_submitted_qc>July 18, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 20, 2023</results_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Pierce Boyne</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Rehabilitation</keyword>
  <keyword>Locomotion</keyword>
  <keyword>Aerobic</keyword>
  <keyword>Intensity</keyword>
  <keyword>Dosing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We deposited the final, de-identified dataset and data documentation into the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH) archive (URL below)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data are available now and should remain available indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Established by the repository</ipd_access_criteria>
    <ipd_url>https://dash.nichd.nih.gov/study/424597</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>424597</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://dash.nichd.nih.gov/study/424597</doc_url>
    </study_doc>
  </study_docs>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03760016/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03760016/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>High-Intensity Interval Training</title>
          <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
        </group>
        <group group_id="P2">
          <title>Moderate-Intensity Aerobic Training</title>
          <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed 4-week Testing</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed 8-week Testing</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>High-Intensity Interval Training</title>
          <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
        </group>
        <group group_id="B2">
          <title>Moderate-Intensity Aerobic Training</title>
          <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="55"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.8" spread="9.9"/>
                    <measurement group_id="B2" value="61.5" spread="9.9"/>
                    <measurement group_id="B3" value="62.6" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Stroke chronicity</title>
          <description>Time interval from stroke onset to consent date</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.7" spread="1.4"/>
                    <measurement group_id="B2" value="2.2" spread="1.2"/>
                    <measurement group_id="B3" value="2.5" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Self-selected gait speed</title>
          <units>meters/second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.65" spread="0.29"/>
                    <measurement group_id="B2" value="0.62" spread="0.33"/>
                    <measurement group_id="B3" value="0.63" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>6-minute walk test distance</title>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="248" spread="136"/>
                    <measurement group_id="B2" value="230" spread="130"/>
                    <measurement group_id="B3" value="239" spread="132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Six-Minute Walk Test Distance</title>
        <description>Total distance walked in 6 minutes in meters</description>
        <time_frame>Change Six-Minute Walk Test Distance from Baseline to 4 Weeks</time_frame>
        <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
        <group_list>
          <group group_id="O1">
            <title>High-Intensity Interval Training</title>
            <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
          </group>
          <group group_id="O2">
            <title>Moderate-Intensity Aerobic Training</title>
            <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
          </group>
        </group_list>
        <measure>
          <title>Six-Minute Walk Test Distance</title>
          <description>Total distance walked in 6 minutes in meters</description>
          <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
          <units>meters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27" lower_limit="6" upper_limit="48"/>
                    <measurement group_id="O2" value="12" lower_limit="-9" upper_limit="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Six-Minute Walk Test Distance</title>
        <description>Total distance walked in 6 minutes in meters</description>
        <time_frame>Change Six-Minute Walk Test Distance from Baseline to 8 Weeks</time_frame>
        <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
        <group_list>
          <group group_id="O1">
            <title>High-Intensity Interval Training</title>
            <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
          </group>
          <group group_id="O2">
            <title>Moderate-Intensity Aerobic Training</title>
            <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
          </group>
        </group_list>
        <measure>
          <title>Six-Minute Walk Test Distance</title>
          <description>Total distance walked in 6 minutes in meters</description>
          <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
          <units>meters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58" lower_limit="39" upper_limit="76"/>
                    <measurement group_id="O2" value="29" lower_limit="9" upper_limit="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Six-Minute Walk Test Distance</title>
        <description>Total distance walked in 6 minutes in meters</description>
        <time_frame>Change Six-Minute Walk Test Distance from Baseline to 12 Weeks</time_frame>
        <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
        <group_list>
          <group group_id="O1">
            <title>High-Intensity Interval Training</title>
            <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
          </group>
          <group group_id="O2">
            <title>Moderate-Intensity Aerobic Training</title>
            <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
          </group>
        </group_list>
        <measure>
          <title>Six-Minute Walk Test Distance</title>
          <description>Total distance walked in 6 minutes in meters</description>
          <population>Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.</population>
          <units>meters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71" lower_limit="49" upper_limit="94"/>
                    <measurement group_id="O2" value="27" lower_limit="3" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comfortable Gait Speed</title>
        <description>From 10-meter walk test, in meters per second</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fast Gait Speed</title>
        <description>From 10-meter walk test, in meters per second</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aerobic Fitness</title>
        <description>Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PROMIS-Fatigue Scale</title>
        <description>An 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total score will be calculated by averaging the scores for each item.</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exercise Capacity</title>
        <description>Time to exhaustion during treadmill graded exercise test, recorded in minutes</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Peak Oxygen Consumption Rate</title>
        <description>Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Metabolic Cost of Gait</title>
        <description>Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>EuroQol 5D-5L (EQ-5D-5L)</title>
        <description>A 6-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, anxiety/depression and overall health. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total score will be calculated by averaging the scores for each item.</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Activities-specific Balance Confidence Scale</title>
        <description>A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score will be calculated by averaging the scores for each item.</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Daily Walking Activity</title>
        <description>Mean daily step count recorded with activity monitor, recorded as steps per day</description>
        <time_frame>4 ,8, 12 weeks</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study</time_frame>
      <group_list>
        <group group_id="E1">
          <title>High-Intensity Interval Training</title>
          <description>High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.</description>
        </group>
        <group group_id="E2">
          <title>Moderate-Intensity Aerobic Training</title>
          <description>Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>fall with fracture</sub_title>
                <description>fall with hip fracture, judged to be unrelated to study procedures</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>seizure</sub_title>
                <description>seizure leading to temporary hospitalization, judged to be unrelated to study procedures</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>delirium</sub_title>
                <description>delirium leading to temporary hospitalization, judged to be unrelated to study procedures</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>stroke</sub_title>
                <description>recurrent stroke, judged to be unrelated to study procedures</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>Fatigue related to treatment</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <description>lightheadedness related to treatment</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <description>Fall without injury related to treatment</description>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain/soreness</sub_title>
                <description>Pain/soreness related to treatment</description>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pierce Boyne</name_or_title>
      <organization>University of Cincinnati</organization>
      <phone>5135587499</phone>
      <email>Pierce.Boyne@uc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03760016
org study id: 2017-5325
secondary id: R01HD093694
nct id: NCT03760016
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to determine the optimal training intensity and the minimum
      training duration needed to maximize immediate improvements in walking capacity in chronic
      stroke. A single-blind, phase II, 3-site randomized controlled trial has been planned. Fifty
      persons >6 months post stroke will randomize to either moderate-intensity aerobic locomotor
      training or high-intensity interval locomotor training; each for 45 minutes, 3x/week for up
      to 36 total sessions over approximately 12 weeks. Clinical measures of walking function,
      aerobic fitness, daily walking activity and quality of life will be assessed at baseline
      (PRE) and after 4, 8 and 12 weeks of training (POST-4WK, POST-8WK, POST-12WK).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Six-Minute Walk Test Distance
time frame: Change Six-Minute Walk Test Distance from Baseline to 4 Weeks
description: Total distance walked in 6 minutes in meters
measure: Six-Minute Walk Test Distance
time frame: Change Six-Minute Walk Test Distance from Baseline to 8 Weeks
description: Total distance walked in 6 minutes in meters
measure: Six-Minute Walk Test Distance
time frame: Change Six-Minute Walk Test Distance from Baseline to 12 Weeks
description: Total distance walked in 6 minutes in meters
measure: Comfortable Gait Speed
time frame: 4 ,8, 12 weeks
description: From 10-meter walk test, in meters per second
measure: Fast Gait Speed
time frame: 4 ,8, 12 weeks
description: From 10-meter walk test, in meters per second
measure: Aerobic Fitness
time frame: 4 ,8, 12 weeks
description: Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute
measure: PROMIS-Fatigue Scale
time frame: 4 ,8, 12 weeks
description: An 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total score will be calculated by averaging the scores for each item.
measure: Exercise Capacity
time frame: 4 ,8, 12 weeks
description: Time to exhaustion during treadmill graded exercise test, recorded in minutes
measure: Peak Oxygen Consumption Rate
time frame: 4 ,8, 12 weeks
description: Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute
measure: Metabolic Cost of Gait
time frame: 4 ,8, 12 weeks
description: Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter
measure: EuroQol 5D-5L (EQ-5D-5L)
time frame: 4 ,8, 12 weeks
description: A 6-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, anxiety/depression and overall health. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total score will be calculated by averaging the scores for each item.
measure: Activities-specific Balance Confidence Scale
time frame: 4 ,8, 12 weeks
description: A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score will be calculated by averaging the scores for each item.
measure: Daily Walking Activity
time frame: 4 ,8, 12 weeks
description: Mean daily step count recorded with activity monitor, recorded as steps per day
arm group label: Moderate-Intensity Aerobic Training
arm group type: Active Comparator
arm group label: High-Intensity Interval Training
arm group type: Experimental
intervention type: Behavioral
intervention name: Moderate-Intensity Aerobic Training
description: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.
arm group label: Moderate-Intensity Aerobic Training
intervention type: Behavioral
intervention name: High-Intensity Interval Training
description: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.
arm group label: High-Intensity Interval Training
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Pierce Boyne, DPT, PhD
role: Principal Investigator
affiliation: University of Cincinnati
facility: 
facility: 
facility: 
country: United States
citation: Boyne P, Billinger SA, Reisman DS, Awosika OO, Buckley S, Burson J, Carl D, DeLange M, Doren S, Earnest M, Gerson M, Henry M, Horning A, Khoury JC, Kissela BM, Laughlin A, McCartney K, McQuaid T, Miller A, Moores A, Palmer JA, Sucharew H, Thompson ED, Wagner E, Ward J, Wasik EP, Whitaker AA, Wright H, Dunning K. Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Apr 1;80(4):342-351. doi: 10.1001/jamaneurol.2023.0033.
PMID: 36822187
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: Pierce Boyne
investigator title: Associate Professor
mesh term: Stroke
sharing ipd: Yes
ipd description: We deposited the final, de-identified dataset and data documentation into the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH) archive (URL below)
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data are available now and should remain available indefinitely.
ipd access criteria: Established by the repository
ipd url: https://dash.nichd.nih.gov/study/424597
study doc: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 