xml: <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/NCT06011876</url>
    </required_header>
    <id_info>
      <org_study_id>IRB202202891</org_study_id>
      <secondary_id>W81XWH2210478</secondary_id>
      <nct_id>NCT06011876</nct_id>
    </id_info>
    <brief_title>BioFLO for Respiratory Recovery in SCI</brief_title>
    <official_title>Genetic Biomarkers of Intermittent Hypoxia-Induced Respiratory Motor Plasticity in Chronic SCI</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Florida</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>U.S. Army Medical Research Acquisition Activity</agency>
        <agency_class>U.S. Fed</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 brief (1 min), repeated episodes (~15) of breathing&#xD;
        low oxygen air to stimulate spinal neuroplasticity. Animal and human studies show that AIH&#xD;
        improves motor function after spinal cord injury, particularly with slightly increased carbon&#xD;
        dioxide (hypercapnic AIH; AIHH) and task-specific training. Using a double blind cross-over&#xD;
        design, the study will test whether AIHH improves breathing more than AIH and whether&#xD;
        specific genetic variations are related to individuals' intervention responses.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will consist of two parts - single-session testing days, and respiratory strength&#xD;
        training blocks. If a participant is not eligible to enroll in single-day testing, they will&#xD;
        be asked to enroll in only the respiratory strength training blocks.&#xD;
  &#xD;
        On single-session testing days, participants will be asked to come in on three separate days&#xD;
        they will complete a battery of tests, then be given one of three interventions, and then&#xD;
        complete the same battery of tests. The three interventions are acute intermittent hypoxia&#xD;
        (AIH), acute intermittent hypercapnic-hypoxia (AIHH), or sham acute intermittent hypoxia&#xD;
        (sham AIH). These interventions are explained in more detail below.&#xD;
  &#xD;
        During respiratory strength training blocks, participants will receive five days of AIH,&#xD;
        AIHH, or sham AIH in combination with respiratory strength training, which uses small&#xD;
        hand-held devices to strengthen the muscles used for breathing. Participants will be asked to&#xD;
        complete all three blocks to receive all three interventions. In addition to 5 days of&#xD;
        interventions and respiratory strength training, the respiratory strength training blocks&#xD;
        include testing 1 day, 3 days, and 7 days after the 5 days of respiratory strength training.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2027</completion_date>
    <primary_completion_date type="Anticipated">July 2027</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in motor evoked potential</measure>
      <time_frame>Baseline, and 45-60 minutes after intervention on AIH day, AIHH day, and Sham AIH day</time_frame>
      <description>The change in peak-to-peak amplitude of the motor evoked potential of the diaphragm will be tested using transcranial magnetic stimulation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in maximal inspiratory pressure</measure>
      <time_frame>Baseline, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)</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, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)</time_frame>
      <description>Maximal expiratory pressure is a non-invasive measure of the maximal force achieved when breathing out against an occluded airway.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">62</enrollment>
    <condition>Spinal Cord Injuries</condition>
    <arm_group>
      <arm_group_label>Single-session testing days</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive AIH, AIHH, and sham AIH in random order. Post-testing will occur after each intervention.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Respiratory strength training blocks</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will complete three separate respiratory strength training blocks. In each block, participants will receive 5 days of AIH, 5 days of AIHH, and 5 days of sham AIH in random order, followed by respiratory strength training. Each block will include 5 days of intervention and training, and post-testing 1, 3, and 7 days after intervention and training has concluded.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Acute Intermittent Hypoxia (AIH)</intervention_name>
      <description>AIH (acute intermittent hypoxia) consists of short episodes of low oxygen (9% O2).</description>
      <arm_group_label>Respiratory strength training blocks</arm_group_label>
      <arm_group_label>Single-session testing days</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Acute Intermittent Hypercapnic-Hypoxia (AIHH)</intervention_name>
      <description>AIHH consists of short episodes of low oxygen (9% O2) and elevated carbon dioxide (4% CO2).</description>
      <arm_group_label>Respiratory strength training blocks</arm_group_label>
      <arm_group_label>Single-session testing days</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Sham AIH</intervention_name>
      <description>A single session of sham AIH with episodes of normal room air (21% O2).</description>
      <arm_group_label>Respiratory strength training blocks</arm_group_label>
      <arm_group_label>Single-session testing days</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults 18-70 years of age&#xD;
  &#xD;
            -  Chronic SCI for &gt; 1 year, at or below C-3 to T-12&#xD;
  &#xD;
            -  Incomplete SCI based on residual sensory or 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;
            -  Medically stable with physician clearance&#xD;
  &#xD;
            -  SCI due to non-progressive etiology&#xD;
  &#xD;
            -  20% impairment in maximal inspiratory or expiratory pressure generation, relative to&#xD;
               normative values&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current diagnosis of an additional neurologic condition such as Multiple Sclerosis,&#xD;
               Parkinson disease, stroke, or brain injury&#xD;
  &#xD;
            -  Severe illness or infection, including non-healing decubitus ulcers, untreated bladder&#xD;
               or urinary tract infections, cardiovascular disease, lung disease, active heterotopic&#xD;
               ossification, or uncontrolled hypertension&#xD;
  &#xD;
            -  Severe neuropathic pain&#xD;
  &#xD;
            -  Known pregnancy&#xD;
  &#xD;
            -  Severe recurrent autonomic dysreflexia&#xD;
  &#xD;
          Exclusion for involvement in TMS - History of seizure disorder, uncontrolled migraines,&#xD;
          presence of cardiac pacemaker, metal implants in skull, medications that lower seizure&#xD;
          threshold.&#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, DPT, MHS, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Florida &amp; Brooks Rehabilitation</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Emily J Fox, PT, MHS, PhD</last_name>
      <phone>904-742-2500</phone>
      <email>ejfox@phhp.ufl.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Hannah Snyder, M.S.</last_name>
      <phone>904-345-6910</phone>
      <email>Hannah.snyder@brooksrehab.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Brooks Rehabilitation</name>
        <address>
          <city>Jacksonville</city>
          <state>Florida</state>
          <zip>32216</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>acute intermittent hypoxia</keyword>
    <keyword>spinal cord injury</keyword>
    <keyword>breathing</keyword>
    <keyword>motor function</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>
  
  
text: 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/NCT06011876
  org study id: IRB202202891
  secondary id: W81XWH2210478
  nct id: NCT06011876
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Acute intermittent hypoxia (AIH) involves brief (1 min), repeated episodes (~15) of breathing
        low oxygen air to stimulate spinal neuroplasticity. Animal and human studies show that AIH
        improves motor function after spinal cord injury, particularly with slightly increased carbon
        dioxide (hypercapnic AIH; AIHH) and task-specific training. Using a double blind cross-over
        design, the study will test whether AIHH improves breathing more than AIH and whether
        specific genetic variations are related to individuals' intervention responses.
  This study will consist of two parts - single-session testing days, and respiratory strength
        training blocks. If a participant is not eligible to enroll in single-day testing, they will
        be asked to enroll in only the respiratory strength training blocks.
  
        On single-session testing days, participants will be asked to come in on three separate days
        they will complete a battery of tests, then be given one of three interventions, and then
        complete the same battery of tests. The three interventions are acute intermittent hypoxia
        (AIH), acute intermittent hypercapnic-hypoxia (AIHH), or sham acute intermittent hypoxia
        (sham AIH). These interventions are explained in more detail below.
  
        During respiratory strength training blocks, participants will receive five days of AIH,
        AIHH, or sham AIH in combination with respiratory strength training, which uses small
        hand-held devices to strengthen the muscles used for breathing. Participants will be asked to
        complete all three blocks to receive all three interventions. In addition to 5 days of
        interventions and respiratory strength training, the respiratory strength training blocks
        include testing 1 day, 3 days, and 7 days after the 5 days of respiratory strength training.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Change in motor evoked potential
  time frame: Baseline, and 45-60 minutes after intervention on AIH day, AIHH day, and Sham AIH day
  description: The change in peak-to-peak amplitude of the motor evoked potential of the diaphragm will be tested using transcranial magnetic stimulation.
  measure: Change in maximal inspiratory pressure
  time frame: Baseline, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)
  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, 1 day, 3 days, and 7 days after intervention blocks (daily AIH + respiratory strength training, daily AIHH + respiratory strength training, daily sham AIH + respiratory strength training.)
  description: Maximal expiratory pressure is a non-invasive measure of the maximal force achieved when breathing out against an occluded airway.
  arm group label: Single-session testing days
  arm group type: Experimental
  description: Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive AIH, AIHH, and sham AIH in random order. Post-testing will occur after each intervention.
  arm group label: Respiratory strength training blocks
  arm group type: Experimental
  description: Participants will complete three separate respiratory strength training blocks. In each block, participants will receive 5 days of AIH, 5 days of AIHH, and 5 days of sham AIH in random order, followed by respiratory strength training. Each block will include 5 days of intervention and training, and post-testing 1, 3, and 7 days after intervention and training has concluded.
  intervention type: Other
  intervention name: Acute Intermittent Hypoxia (AIH)
  description: AIH (acute intermittent hypoxia) consists of short episodes of low oxygen (9% O2).
  arm group label: Respiratory strength training blocks
  arm group label: Single-session testing days
  intervention type: Other
  intervention name: Acute Intermittent Hypercapnic-Hypoxia (AIHH)
  description: AIHH consists of short episodes of low oxygen (9% O2) and elevated carbon dioxide (4% CO2).
  arm group label: Respiratory strength training blocks
  arm group label: Single-session testing days
  intervention type: Other
  intervention name: Sham AIH
  description: A single session of sham AIH with episodes of normal room air (21% O2).
  arm group label: Respiratory strength training blocks
  arm group label: Single-session testing days
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Emily Fox, DPT, MHS, PhD
  role: Principal Investigator
  affiliation: University of Florida & Brooks Rehabilitation
  last name: Emily J Fox, PT, MHS, PhD
  phone: 904-742-2500
  email: ejfox@phhp.ufl.edu
  last name: Hannah Snyder, M.S.
  phone: 904-345-6910
  email: Hannah.snyder@brooksrehab.org
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Spinal Cord Injuries
  sharing ipd: No