<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/NCT04472442</url>
  </required_header>
  <id_info>
    <org_study_id>IU2001598586</org_study_id>
    <nct_id>NCT04472442</nct_id>
  </id_info>
  <brief_title>Intermittent Hypoxia Paired With High Intensity Training in Brain Injury</brief_title>
  <official_title>Intermittent Hypoxia Paired With High Intensity Training in Brain Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rehabilitation Hospital of Indiana</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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 central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains&#xD;
      as compared to HIT alone; 2) improvements in gait quality and motor coordination during&#xD;
      walking, and 3) changes in measures of community participation and integration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains&#xD;
      as compared to HIT alone; 2) improvements in gait quality and motor coordination during&#xD;
      walking, and 3) changes in measures of community participation and integration. To test these&#xD;
      hypotheses, the proposed crossover, assessor-blinded, randomized clinical trial (RCT) is&#xD;
      designed to test the effects of safety, feasibility, and preliminary efficacy of HIT+AIH. In&#xD;
      this phase I-II trial, patients &gt;6 months post-BI with mobility deficits will be allocated to&#xD;
      5 weeks (15 sessions) of HIT+AIH or HIT alone. Blinded assessments will be performed prior to&#xD;
      and following training paradigms to address 3 specific aims.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Actual">June 30, 2023</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>2-arm, randomized, crossover trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Blinding of both participant with actual vs sham treatment and blinding of primary outcome assessments</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in gait speed</measure>
    <time_frame>Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 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 1 after 6 weeks, Baseline 2, Post 2 after 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>Metabolic capacity</measure>
    <time_frame>Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 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="Anticipated">20</enrollment>
  <condition>Brain Injuries</condition>
  <arm_group>
    <arm_group_label>High Intensity Training with Intermittent Hypoxia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The primary goal will be provide acute intermittent hypoxia (9% PO2; 1 min on 1 min off) prior to stepping training while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). 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>High Intensity Training with Sham Hypoxia</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The primary goal will be provide sham intermittent hypoxia (20% PO2) prior to performing 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). 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>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Intermittent hypoxia</intervention_name>
    <description>Acute intermittent treatment (AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. AIH (using 9% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented.&#xD;
High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).</description>
    <arm_group_label>High Intensity Training with Intermittent Hypoxia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham hypoxia</intervention_name>
    <description>Sham acute intermittent treatment (sham AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. Sham AIH (using 20% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented.&#xD;
High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).</description>
    <arm_group_label>High Intensity Training with Sham Hypoxia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 6 months post 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 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_contact>
    <last_name>Thomas Hornby, PT, PhD</last_name>
    <phone>(312) 329-2353</phone>
    <email>tghornby@Iu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chris Henderson, PT, PhD</last_name>
    <phone>(312) 329-2353</phone>
    <email>henderce@iu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rehabilitation Hospital of Indiana</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46254</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Hornby, PT, PhD</last_name>
      <phone>317-329-2353</phone>
      <email>tghornby@Iu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>August 23, 2023</last_update_submitted>
  <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 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 Physcial Medicine &amp; Rehabilitation</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD available per request</ipd_description>
  </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/NCT04472442
org study id: IU2001598586
nct id: NCT04472442
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains
      as compared to HIT alone; 2) improvements in gait quality and motor coordination during
      walking, and 3) changes in measures of community participation and integration.
The central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains
      as compared to HIT alone; 2) improvements in gait quality and motor coordination during
      walking, and 3) changes in measures of community participation and integration. To test these
      hypotheses, the proposed crossover, assessor-blinded, randomized clinical trial (RCT) is
      designed to test the effects of safety, feasibility, and preliminary efficacy of HIT+AIH. In
      this phase I-II trial, patients >6 months post-BI with mobility deficits will be allocated to
      5 weeks (15 sessions) of HIT+AIH or HIT alone. Blinded assessments will be performed prior to
      and following training paradigms to address 3 specific aims.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 2-arm, randomized, crossover trial
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Blinding of both participant with actual vs sham treatment and blinding of primary outcome assessments
measure: Change in gait speed
time frame: Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 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 1 after 6 weeks, Baseline 2, Post 2 after 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: Metabolic capacity
time frame: Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 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 Training with Intermittent Hypoxia
arm group type: Experimental
description: The primary goal will be provide acute intermittent hypoxia (9% PO2; 1 min on 1 min off) prior to stepping training while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). 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: High Intensity Training with Sham Hypoxia
arm group type: Sham Comparator
description: The primary goal will be provide sham intermittent hypoxia (20% PO2) prior to performing 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). 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.
intervention type: Procedure
intervention name: Intermittent hypoxia
description: Acute intermittent treatment (AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. AIH (using 9% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented.
High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).
arm group label: High Intensity Training with Intermittent Hypoxia
intervention type: Procedure
intervention name: Sham hypoxia
description: Sham acute intermittent treatment (sham AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. Sham AIH (using 20% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented.
High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).
arm group label: High Intensity Training with Sham Hypoxia
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Thomas Hornby, PT, PhD
phone: (312) 329-2353
email: tghornby@Iu.edu
last name: Chris Henderson, PT, PhD
phone: (312) 329-2353
email: henderce@iu.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: George Hornby
investigator title: Professor of Physcial Medicine & Rehabilitation
mesh term: Brain Injuries
mesh term: Hypoxia
mesh term: Wounds and Injuries
sharing ipd: No
ipd description: IPD available per request