<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/NCT04503473</url>
  </required_header>
  <id_info>
    <org_study_id>1911962819</org_study_id>
    <nct_id>NCT04503473</nct_id>
  </id_info>
  <brief_title>Locomotor Recovery Following Traumatic Brain Injury</brief_title>
  <acronym>TBI_IU</acronym>
  <official_title>Locomotor Recovery Following Traumatic Brain Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</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 purpose of this study is to investigate the effectiveness of two different walking&#xD;
      training interventions on the recovery of strength, mobility, walking and other measures of&#xD;
      health in individuals following traumatic brain injury. During this study, participants will&#xD;
      aim to complete up to 15 training sessions over 4-5 weeks of each intervention with at least&#xD;
      a 4 week break between interventions. Each training session will last approximately 1 hour,&#xD;
      while testing sessions performed at the beginning and end of each intervention will last&#xD;
      approximately 3-4 hours. Participation in this research study may last up to 6 months&#xD;
      including screening and baseline testing. The possible benefits to participant from&#xD;
      participation in this study include increased strength of the participants leg muscles and&#xD;
      improved walking ability&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary goal of the proposed study is to identify the contributions of the amount of&#xD;
      task-specific practice on locomotor (i.e., walking) recovery in patients with (&gt; 6 Months)&#xD;
      traumatic brain injury (TBI). The investigator will do this by building on our previous work&#xD;
      directed towards identifying the essential exercise training parameters that maximize&#xD;
      locomotor recovery. Consistent with principles of motor learning and exercise physiology, the&#xD;
      investigator contend that certain training (i.e., dosage) parameters of physical&#xD;
      rehabilitation, including the type (specificity) and amount of task practice, are critical to&#xD;
      mobility outcomes following neurological injury. Previous work suggests these training&#xD;
      parameters may influence locomotor recovery in patients with other neurological disorders&#xD;
      (i.e., stroke), although few studies have attempted to delineate similar contributions of&#xD;
      amount of task-specific practice in neurologic injury. Indeed, no studies have carefully&#xD;
      controlled these training parameters during physical rehabilitation of patients with&#xD;
      neurologic injury, and such interventions are rarely utilized in the clinical setting.&#xD;
      Reasons for these knowledge gaps from other rehabilitation studies to patients with&#xD;
      neurologic injury or lack of clinical implementation are unclear, but may be due to adherence&#xD;
      to traditional rehabilitation theories. One concern is that practicing only stepping tasks&#xD;
      reduces attention towards hallmark physical impairments following neurologic injury, such as&#xD;
      loss of strength or postural stability, which are considered primary determinants of&#xD;
      decreased mobility. Only a few studies have addressed whether providing only structured&#xD;
      stepping training can mitigate these impairments without their explicit practice, but not in&#xD;
      the neurologic injury population. A related concern is that focused stepping training without&#xD;
      significant attention towards impairments or gait quality may exaggerate altered movement&#xD;
      strategies, which could be reinforced with repeated practice. However, there is little data&#xD;
      to suggest &quot;worsening&quot; of abnormal gait patterns following high intensity training. Rather,&#xD;
      recent findings suggest patients demonstrate more normal kinematics. If focused task specific&#xD;
      (i.e., stepping) training is to be applied clinically, participant must delineate its&#xD;
      contributions towards improving locomotor function, and their effects on underlying&#xD;
      impairments and gait kinematics.&#xD;
&#xD;
      Central hypotheses are that stepping training in TBI results in:1) greater locomotor gains as&#xD;
      compared to non-specific interventions; 2) gains in selected impairments underlying gait&#xD;
      dysfunction (i.e., strength and metabolic capacity and efficiency); and, 3) improvements in&#xD;
      gait quality. To test these hypotheses, the proposed crossover, assessor-blinded, randomized&#xD;
      clinical trial (RCT) is designed to test the effects of specificity of rehabilitation&#xD;
      training applied early-post-stroke. In this RCT, patients &gt; 6 post-TBI will be allocated ≤ 15&#xD;
      sessions over approximately 4-5 weeks of high-intensity stepping training or conventional&#xD;
      therapy. Importantly, training intensity will be held constant to account for this potential&#xD;
      confounding factor. Blinded assessments will be performed prior to and following each&#xD;
      training paradigm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 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>Crossover Assignment</intervention_model>
    <intervention_model_description>Baseline characteristics and training parameters (steps, intensity parameters) will be compared between treatment groups using independent group comparisons. (ANOVA, Kruskal-Wallis, or Chi-squared tests as appropriate).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Gait speed</measure>
    <time_frame>Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks</time_frame>
    <description>Gait speed is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait speed will be measured at self-selected speeds (SSS; instructions to &quot;walk at normal comfortable pace&quot;) and fastest-possible speed (FS: &quot;as fast as you safely can&quot;) using the Zeno Walkway (Protokinetics, Haverton, PA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Endurance</measure>
    <time_frame>Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks</time_frame>
    <description>Endurance is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait endurance will be tested using the 6MWT (m) with instructions similar to SSS to minimize fall risk.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Strength</measure>
    <time_frame>Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 6 weeks</time_frame>
    <description>• Peak volitional strength - We will assess strength while subjects are seated in an adjustable height chair of a testing apparatus. Three trials of peak isometric volitional hip, knee and ankle torques will be determined bilaterally with significant verbal encouragement for 3-5 sec, and &gt; 1 min duration between trials.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gait quality</measure>
    <time_frame>Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks</time_frame>
    <description>Gait kinematics: Lower limb kinematics will be collected using an 8-camera motion capture system and 3-dimensional movement of 1&quot; reflective markers affixed to the pelvis/legs. Spatiotemporal metrics will be extracted from the data, with primary measures of peak speed, stride length, cadence. All measures will be compared between fastest speeds achieved at BSL and POST, and at POST speeds matched to BSL peak speed to allow kinematic comparisons while controlling for speeds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in metabolic capacity</measure>
    <time_frame>Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks</time_frame>
    <description>peak metabolic capacity will be observed during graded exercise testing on a treadmill wtih peak oxygen consumption</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Traumatic Brain Injury (TBI)</condition>
  <arm_group>
    <arm_group_label>High Intensity Stepping Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The primary goal will be to perform continuous stepping while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). We will also record Ratings of Perceived Exertion (RPE) every 3-5 minutes, with goals of 15-18. Sessions will be divided into ~10 minute increments (~25% of sessions) between speed-dependent treadmill training (described above for treadmill stepping), skill-dependent treadmill training, overground training, and stair climbing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions. The type of therapeutic activities is based on published normative data of typical activities performed during clinical physical therapy sessions with focus on strengthening activities (25% of session); balance activities (25%); locomotor activities (25%), and combined stretching exercises (10-15%) and transfers (10-15%). Intensity of activities will be targeted at 30-40% of their HR reserve in attempts to maintain consistent intensities between training groups.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>High Intensity Stepping Training</intervention_name>
    <description>The goals will be to maximize stepping activity at high intensities for 40 minutes per 1 hour session, with rest breaks as needed&#xD;
Conventional Therapy: : Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions</description>
    <arm_group_label>High Intensity Stepping Training</arm_group_label>
    <other_name>HIT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Conventional Therapy</intervention_name>
    <description>Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions</description>
    <arm_group_label>Conventional Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 6 months post traumatic brain injury&#xD;
&#xD;
          -  18-75 years old&#xD;
&#xD;
          -  ability to walk without physical assistance&#xD;
&#xD;
          -  Self selected walking speed of 0.01-1.0 m/s&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt;18 years old&#xD;
&#xD;
          -  &gt;75 years old&#xD;
&#xD;
          -  self selected walking speed of &gt; 1.0 m/s&#xD;
&#xD;
          -  &lt; 3 months from botulinum toxin injection&#xD;
&#xD;
          -  Above the knee brace&#xD;
&#xD;
          -  Currently receiving physical therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George Hornby, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rehabilitation Hospital of Indiana</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46254</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 16, 2019</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>George Hornby</investigator_full_name>
    <investigator_title>Professor of Physical Medicine &amp; Rehabilitation</investigator_title>
  </responsible_party>
  <keyword>Traumatic Brain Injury</keyword>
  <keyword>TBI</keyword>
  <keyword>Walking</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- 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/NCT04503473
org study id: 1911962819
nct id: NCT04503473
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the effectiveness of two different walking
      training interventions on the recovery of strength, mobility, walking and other measures of
      health in individuals following traumatic brain injury. During this study, participants will
      aim to complete up to 15 training sessions over 4-5 weeks of each intervention with at least
      a 4 week break between interventions. Each training session will last approximately 1 hour,
      while testing sessions performed at the beginning and end of each intervention will last
      approximately 3-4 hours. Participation in this research study may last up to 6 months
      including screening and baseline testing. The possible benefits to participant from
      participation in this study include increased strength of the participants leg muscles and
      improved walking ability
The primary goal of the proposed study is to identify the contributions of the amount of
      task-specific practice on locomotor (i.e., walking) recovery in patients with (> 6 Months)
      traumatic brain injury (TBI). The investigator will do this by building on our previous work
      directed towards identifying the essential exercise training parameters that maximize
      locomotor recovery. Consistent with principles of motor learning and exercise physiology, the
      investigator contend that certain training (i.e., dosage) parameters of physical
      rehabilitation, including the type (specificity) and amount of task practice, are critical to
      mobility outcomes following neurological injury. Previous work suggests these training
      parameters may influence locomotor recovery in patients with other neurological disorders
      (i.e., stroke), although few studies have attempted to delineate similar contributions of
      amount of task-specific practice in neurologic injury. Indeed, no studies have carefully
      controlled these training parameters during physical rehabilitation of patients with
      neurologic injury, and such interventions are rarely utilized in the clinical setting.
      Reasons for these knowledge gaps from other rehabilitation studies to patients with
      neurologic injury or lack of clinical implementation are unclear, but may be due to adherence
      to traditional rehabilitation theories. One concern is that practicing only stepping tasks
      reduces attention towards hallmark physical impairments following neurologic injury, such as
      loss of strength or postural stability, which are considered primary determinants of
      decreased mobility. Only a few studies have addressed whether providing only structured
      stepping training can mitigate these impairments without their explicit practice, but not in
      the neurologic injury population. A related concern is that focused stepping training without
      significant attention towards impairments or gait quality may exaggerate altered movement
      strategies, which could be reinforced with repeated practice. However, there is little data
      to suggest "worsening" of abnormal gait patterns following high intensity training. Rather,
      recent findings suggest patients demonstrate more normal kinematics. If focused task specific
      (i.e., stepping) training is to be applied clinically, participant must delineate its
      contributions towards improving locomotor function, and their effects on underlying
      impairments and gait kinematics.

      Central hypotheses are that stepping training in TBI results in:1) greater locomotor gains as
      compared to non-specific interventions; 2) gains in selected impairments underlying gait
      dysfunction (i.e., strength and metabolic capacity and efficiency); and, 3) improvements in
      gait quality. To test these hypotheses, the proposed crossover, assessor-blinded, randomized
      clinical trial (RCT) is designed to test the effects of specificity of rehabilitation
      training applied early-post-stroke. In this RCT, patients > 6 post-TBI will be allocated ≤ 15
      sessions over approximately 4-5 weeks of high-intensity stepping training or conventional
      therapy. Importantly, training intensity will be held constant to account for this potential
      confounding factor. Blinded assessments will be performed prior to and following each
      training paradigm.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Baseline characteristics and training parameters (steps, intensity parameters) will be compared between treatment groups using independent group comparisons. (ANOVA, Kruskal-Wallis, or Chi-squared tests as appropriate).
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Gait speed
time frame: Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks
description: Gait speed is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait speed will be measured at self-selected speeds (SSS; instructions to "walk at normal comfortable pace") and fastest-possible speed (FS: "as fast as you safely can") using the Zeno Walkway (Protokinetics, Haverton, PA).
measure: Change in Endurance
time frame: Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks
description: Endurance is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait endurance will be tested using the 6MWT (m) with instructions similar to SSS to minimize fall risk.
measure: Change in Strength
time frame: Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 6 weeks
description: • Peak volitional strength - We will assess strength while subjects are seated in an adjustable height chair of a testing apparatus. Three trials of peak isometric volitional hip, knee and ankle torques will be determined bilaterally with significant verbal encouragement for 3-5 sec, and > 1 min duration between trials.
measure: Change in gait quality
time frame: Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks
description: Gait kinematics: Lower limb kinematics will be collected using an 8-camera motion capture system and 3-dimensional movement of 1" reflective markers affixed to the pelvis/legs. Spatiotemporal metrics will be extracted from the data, with primary measures of peak speed, stride length, cadence. All measures will be compared between fastest speeds achieved at BSL and POST, and at POST speeds matched to BSL peak speed to allow kinematic comparisons while controlling for speeds.
measure: Change in metabolic capacity
time frame: Baseline 1, Post 6 weeks, Baseline 2, Post 6 weeks
description: peak metabolic capacity will be observed during graded exercise testing on a treadmill wtih peak oxygen consumption
arm group label: High Intensity Stepping Training
arm group type: Experimental
description: The primary goal will be to perform continuous stepping while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). We will also record Ratings of Perceived Exertion (RPE) every 3-5 minutes, with goals of 15-18. Sessions will be divided into ~10 minute increments (~25% of sessions) between speed-dependent treadmill training (described above for treadmill stepping), skill-dependent treadmill training, overground training, and stair climbing.
arm group label: Conventional Therapy
arm group type: Active Comparator
description: Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions. The type of therapeutic activities is based on published normative data of typical activities performed during clinical physical therapy sessions with focus on strengthening activities (25% of session); balance activities (25%); locomotor activities (25%), and combined stretching exercises (10-15%) and transfers (10-15%). Intensity of activities will be targeted at 30-40% of their HR reserve in attempts to maintain consistent intensities between training groups.
intervention type: Behavioral
intervention name: High Intensity Stepping Training
description: The goals will be to maximize stepping activity at high intensities for 40 minutes per 1 hour session, with rest breaks as needed
Conventional Therapy: : Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions
arm group label: High Intensity Stepping Training
other name: HIT
intervention type: Behavioral
intervention name: Conventional Therapy
description: Participants provided conventional therapy will perform various standardized exercise tasks during 40 minutes of 1 hr sessions
arm group label: Conventional Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: George Hornby, PhD
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: George Hornby
investigator title: Professor of Physical Medicine & Rehabilitation
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries