<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/NCT03833674</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201802672</org_study_id>
    <secondary_id>W81XWH-18-1-0718</secondary_id>
    <nct_id>NCT03833674</nct_id>
  </id_info>
  <brief_title>FLO2 for Recovery After SCI</brief_title>
  <official_title>Acute Intermittent Hypoxia and Respiratory Strength Training to Improve Breathing Function After Spinal Cord Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brooks Rehabilitation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute intermittent hypoxia (AIH) involves short (~1-2min) bouts of breathing low oxygen air&#xD;
      to stimulate spinal neuroplasticity. Studies in rodents and humans indicate that AIH improves&#xD;
      motor function after spinal cord injury (SCI). This study will use a double blind, cross-over&#xD;
      design to test if the combination of AIH and respiratory strength training improves breathing&#xD;
      function more than either approach alone in adults with chronic SCI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, causing&#xD;
      muscle paralysis and decreased breathing capacity. Since respiratory impairment is the major&#xD;
      cause of illness and death with SCI, it is critical to devise new strategies to restore&#xD;
      breathing function.&#xD;
&#xD;
      Repetitive exposure to brief episodes of low oxygen (acute intermittent hypoxia or AIH) has&#xD;
      demonstrated to increase respiratory function in humans with chronic SCI. Additionally&#xD;
      pre-clinical studies demonstrate that AIH-induced functional benefits are enhanced by&#xD;
      combining AIH with task-specific training. The investigator's central hypothesis is that&#xD;
      combined daily AIH (dAIH) and respiratory strength training will elicit greater and more&#xD;
      sustained gains in respiratory function than either treatment alone in people with chronic&#xD;
      SCI.&#xD;
&#xD;
      This study is a double-blind, randomized, cross-over design where participants will complete&#xD;
      4 random-ordered blocks, consisting of a 5-day intervention followed by a 3-week washout&#xD;
      period, during which 1-day, 3-day, and 1-week post-tests will be conducted. Participants will&#xD;
      include 53 adults with chronic, incomplete SCI with &gt;20% respiratory impairment based on&#xD;
      maximal inspiratory or expiratory pressure generation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 15, 2020</start_date>
  <completion_date type="Anticipated">November 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Participants will complete a battery of clinical assessments and 4 randomly ordered intervention and testing blocks. Blocks 1, 2 and 3 include a 5 day intervention (e.g., dAIH and/or respiratory training) or sham protocol, followed by a 3-week washout period, with follow up measurements at 1 day, 3 days and 1 week post-intervention. The final block includes a 5-day protocol followed by 1-day, 3-day and 1-week post-tests.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants and the clinical evaluator will be informed of possible interventions but will be blinded to the gas mixture (hypoxic vs normoxic air) used during each AIH intervention.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in maximal inspiratory pressure</measure>
    <time_frame>Baseline, Day 1, Day 6, Day 8, Day 15</time_frame>
    <description>Maximal inspiratory pressure is a non-invasive measure of the maximal force achieved when breathing in against an occluded airway.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in maximal expiratory pressure</measure>
    <time_frame>Baseline, Day 1, Day 6, Day 8, Day 15</time_frame>
    <description>Maximal expiratory pressure is a non-invasive measure of the maximal force generated when breathing out against an occluded airway.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">53</enrollment>
  <condition>Spinal Cord Injury (SCI)</condition>
  <arm_group>
    <arm_group_label>Adults with incomplete SCI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adults with chronic, incomplete SCI who have &gt;20% impairment in respiratory function, who will complete a battery of clinical assessments and 4 randomly ordered intervention and testing blocks (Daily AIH Block, Sham dAIH Block, Respiratory Strength Training Block and AIH + Strength Training Block).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Daily AIH Block</intervention_name>
    <description>Daily sessions of AIH (dAIH) with use of short episodes of low oxygen (9% O2)</description>
    <arm_group_label>Adults with incomplete SCI</arm_group_label>
    <other_name>dAIH Block</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham dAIH Block</intervention_name>
    <description>Daily sessions of sham dAIH which includes breathing room air (21% O2)</description>
    <arm_group_label>Adults with incomplete SCI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Respiratory Strength Training Block</intervention_name>
    <description>Respiratory strength training using a hand-held device that resists inspiration or expiration.</description>
    <arm_group_label>Adults with incomplete SCI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>AIH + Strength Training Block</intervention_name>
    <description>AIH followed by respiratory strength training.</description>
    <arm_group_label>Adults with incomplete SCI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic incomplete SCI for ≥ 1 year at or below C-1 to T-12&#xD;
&#xD;
          -  Incomplete SCI based on residual sensory and motor function below the level of the&#xD;
             injury or injury classification of B, C, D at initial screening according to the&#xD;
             American Spinal Injury Association Impairment Classification and the International&#xD;
             Standards for the Neurological Classification of SCI&#xD;
&#xD;
        -OR-&#xD;
&#xD;
        Chronic complete SCI for ≥ 1 year at or below C-4 to T-12&#xD;
&#xD;
          -  Complete SCI based on the absence of residual sensory or motor function below the&#xD;
             level of injury or injury classification of A at initial screening according to the&#xD;
             American Spinal Injury Association Impairment Classification and the International&#xD;
             Standards for the Neurological Classification of SCI.&#xD;
&#xD;
          -  Medically stable with clearance from physician&#xD;
&#xD;
          -  SCI due to non-progressive etiology&#xD;
&#xD;
          -  &gt;20% impairment in maximal inspiratory or expiratory pressure generation, relative to&#xD;
             established normative values.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis of an additional neurologic condition such as multiple sclerosis,&#xD;
             Parkinson's disease, stroke, or brain injury&#xD;
&#xD;
          -  Presence of unstable or uncontrolled medical conditions such as cardiovascular&#xD;
             disease, myocardial infarction, &lt;1 year lung disease, infections, hypertension,&#xD;
             heterotopic ossification.&#xD;
&#xD;
          -  Severe neuropathic pain&#xD;
&#xD;
          -  Known pregnancy&#xD;
&#xD;
          -  Severe recurrent autonomic dysreflexia&#xD;
&#xD;
          -  History of seizure disorder &lt; 1 year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emily Fox, PT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gordon Mitchell, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alicia Vose, MA CCC-SLP</last_name>
    <phone>860-912-8156</phone>
    <email>avose1@ufl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emily J Fox, DPT, PhD</last_name>
    <email>ejfox@ufl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Brooks Rehabilitation Hospital</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lou DeMark, DPT</last_name>
      <phone>904-345-8968</phone>
      <email>lou.demark@brooksrehab.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute intermittent hypoxia (AIH)</keyword>
  <keyword>spinal neuroplasticity</keyword>
  <keyword>motor function</keyword>
  <keyword>respiratory strength training</keyword>
  <keyword>respiration</keyword>
  <keyword>breathing</keyword>
  <keyword>plasticity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03833674
org study id: IRB201802672
secondary id: W81XWH-18-1-0718
nct id: NCT03833674
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Acute intermittent hypoxia (AIH) involves short (~1-2min) bouts of breathing low oxygen air
      to stimulate spinal neuroplasticity. Studies in rodents and humans indicate that AIH improves
      motor function after spinal cord injury (SCI). This study will use a double blind, cross-over
      design to test if the combination of AIH and respiratory strength training improves breathing
      function more than either approach alone in adults with chronic SCI.
Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, causing
      muscle paralysis and decreased breathing capacity. Since respiratory impairment is the major
      cause of illness and death with SCI, it is critical to devise new strategies to restore
      breathing function.

      Repetitive exposure to brief episodes of low oxygen (acute intermittent hypoxia or AIH) has
      demonstrated to increase respiratory function in humans with chronic SCI. Additionally
      pre-clinical studies demonstrate that AIH-induced functional benefits are enhanced by
      combining AIH with task-specific training. The investigator's central hypothesis is that
      combined daily AIH (dAIH) and respiratory strength training will elicit greater and more
      sustained gains in respiratory function than either treatment alone in people with chronic
      SCI.

      This study is a double-blind, randomized, cross-over design where participants will complete
      4 random-ordered blocks, consisting of a 5-day intervention followed by a 3-week washout
      period, during which 1-day, 3-day, and 1-week post-tests will be conducted. Participants will
      include 53 adults with chronic, incomplete SCI with >20% respiratory impairment based on
      maximal inspiratory or expiratory pressure generation.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Participants will complete a battery of clinical assessments and 4 randomly ordered intervention and testing blocks. Blocks 1, 2 and 3 include a 5 day intervention (e.g., dAIH and/or respiratory training) or sham protocol, followed by a 3-week washout period, with follow up measurements at 1 day, 3 days and 1 week post-intervention. The final block includes a 5-day protocol followed by 1-day, 3-day and 1-week post-tests.
primary purpose: Treatment
masking: None (Open Label)
masking description: Participants and the clinical evaluator will be informed of possible interventions but will be blinded to the gas mixture (hypoxic vs normoxic air) used during each AIH intervention.
measure: Change in maximal inspiratory pressure
time frame: Baseline, Day 1, Day 6, Day 8, Day 15
description: Maximal inspiratory pressure is a non-invasive measure of the maximal force achieved when breathing in against an occluded airway.
measure: Change in maximal expiratory pressure
time frame: Baseline, Day 1, Day 6, Day 8, Day 15
description: Maximal expiratory pressure is a non-invasive measure of the maximal force generated when breathing out against an occluded airway.
arm group label: Adults with incomplete SCI
arm group type: Experimental
description: Adults with chronic, incomplete SCI who have >20% impairment in respiratory function, who will complete a battery of clinical assessments and 4 randomly ordered intervention and testing blocks (Daily AIH Block, Sham dAIH Block, Respiratory Strength Training Block and AIH + Strength Training Block).
intervention type: Other
intervention name: Daily AIH Block
description: Daily sessions of AIH (dAIH) with use of short episodes of low oxygen (9% O2)
arm group label: Adults with incomplete SCI
other name: dAIH Block
intervention type: Other
intervention name: Sham dAIH Block
description: Daily sessions of sham dAIH which includes breathing room air (21% O2)
arm group label: Adults with incomplete SCI
intervention type: Other
intervention name: Respiratory Strength Training Block
description: Respiratory strength training using a hand-held device that resists inspiration or expiration.
arm group label: Adults with incomplete SCI
intervention type: Other
intervention name: AIH + Strength Training Block
description: AIH followed by respiratory strength training.
arm group label: Adults with incomplete SCI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Emily Fox, PT, PhD
role: Principal Investigator
affiliation: University of Florida
last name: Gordon Mitchell, PhD
role: Principal Investigator
affiliation: University of Florida
last name: Alicia Vose, MA CCC-SLP
phone: 860-912-8156
email: avose1@ufl.edu
last name: Emily J Fox, DPT, PhD
email: ejfox@ufl.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Spinal Cord Injuries
sharing ipd: No