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/NCT06019949</url>
    </required_header>
    <id_info>
      <org_study_id>23.0570</org_study_id>
      <secondary_id>1R01HL168294</secondary_id>
      <nct_id>NCT06019949</nct_id>
    </id_info>
    <brief_title>Spinal Cord Stimulation for Respiratory Rehabilitation in Patients With Chronic Spinal Cord Injury</brief_title>
    <official_title>Neuromodulatory Rehabilitation for Respiratory Motor Function in Individuals With Chronic Spinal Cord Injury</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Louisville</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Louisville</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Respiratory complications are among the leading causes of death in patients with chronic&#xD;
        spinal cord injury (SCI). Our previous work showed that pulmonary function can be improved by&#xD;
        using our original respiratory training method. However, the effectiveness of this&#xD;
        intervention is limited due to the disruption of brain-spinal connections and consequently&#xD;
        lowered spinal cord activity below the injury level. Our recent studies showed that&#xD;
        electrical stimulation of the spinal cord below the level of injury leads to increased&#xD;
        ventilation which indicates activation of the spinal cord structures related to respiration.&#xD;
        These findings indicate that spinal cord stimulation can be a promising therapeutic additive&#xD;
        to the treatment. The goal of this study is to justify the establishment of a new direction&#xD;
        in rehabilitation for patients with SCI by using a non-invasive spinal cord stimulation in&#xD;
        combination with respiratory training.&#xD;
  &#xD;
        Our aims are: 1) to evaluate the effects of such stimulation applied to the injured spinal&#xD;
        cord on pulmonary function and respiratory muscle activity, and 2) to evaluate the&#xD;
        effectiveness and therapeutic mechanisms of the spinal cord stimulation combined with&#xD;
        respiratory training. Thirty-six individuals with chronic SCI will be recruited and assigned&#xD;
        to three groups to receive respiratory training or spinal cord stimulation alone or a&#xD;
        combination of them. All participants will be tested before and after cycles of experimental&#xD;
        procedures with/or without stimulation. Our hypotheses will be confirmed if the respiratory&#xD;
        training combined with spinal cord stimulation results in the most enhanced positive effects.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a respiratory rehabilitation-based clinical study consisting of physiologically and&#xD;
        functionally relevant mapping of respiratory function that enhances our knowledge of&#xD;
        neurophysiological modulation evoked by non-invasive spinal cord Transcutaneous Stimulation&#xD;
        (scTS) and contributes to the development of the next generation of rehabilitative&#xD;
        approaches. Following the screening process and recruiting, the research subjects will&#xD;
        undergo the following procedures: Subjects (total n=36) will be randomly assigned to three&#xD;
        groups and will undergo baseline assessments; evaluations before and after 80 sessions of&#xD;
        specific intervention (Respiratory Training /RT/ alone, scTS alone, or RT in combination with&#xD;
        scTS); and during 16 week-long follow up period.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 10, 2023</start_date>
    <completion_date type="Anticipated">April 10, 2030</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2028</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>
      <intervention_model_description>Thirty-six SCI participants will be randomly assigned to three groups (n=12 in each group): those who receive RT alone, scTS alone, or a combination of both (scTS+RT).&#xD;
  After screening and recruitment, primary and secondary outcome measurements will be obtained in the Lab at the following time points: 1) Pre-intervention, after 30-days without any stimulation and/or intervention, 2) Post mapping, (participants with scTS), 3) Post Session #40 (after 8 weeks of intervention), 4) Post Session #80 (after 16 weeks of intervention), and 5) twice during 16-weeks Follow-up Period. In total, it is anticipated that 6 measurements will be obtained for each participant with scTS and 5 measurements for participants without scTS.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Unidentified data sets will be processed and evaluated by the research staff not directly involved in experimental procedures.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum Expiratory Pressure (PEmax).</measure>
      <time_frame>Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Standard Spirometry measurement.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Inspiratory Pressure (PImax).</measure>
      <time_frame>Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Standard Spirometry measurement.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Surface electromyography (sEMG) Similarity Index (SI)</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Respiratory multi-muscle activation measures assessed using standard surface electromyography.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Forced Vital Capacity (FVC).</measure>
      <time_frame>Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Standard Spirometry measurement.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Forced Expiratory Volume in 1 second (FEV1).</measure>
      <time_frame>Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Standard Spirometry measurement.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Baroreflex blood pressure sensitivity (BRS).</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measure of the beat-to-beat blood pressure variability assessed during a Valsalva maneuver.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Baroreflex heart rate sensitivity (BRS).</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measure of the beat-to-beat heart rate variability assessed during a Valsalva maneuver.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Baroreflex blood pressure effectiveness index (BEI).</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measure of the beat-to-beat blood pressure variability assessed during a Valsalva maneuver.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Baroreflex heart rate effectiveness index (BEI).</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measure of the beat-to-beat heart rate variability assessed during a Valsalva maneuver.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Spinal Cord Independence Measure (SCIM, Version III).</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measures the level of self-care.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>The Craig Handicap Assessment &amp; Reporting Technique (CHART) Questionnaire.</measure>
      <time_frame>Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.</time_frame>
      <description>Measures the level of handicap in a community setting.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Spinal Cord Injuries</condition>
    <condition>Respiration Disorders</condition>
    <arm_group>
      <arm_group_label>Training (RT) group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>80 scTS sessions will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) device applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes. During the intervention, optimally configured scTS will be delivered based on the measures assessed during mapping sessions. The scTS with 5 mA-sub-motor threshold intensity with optimal frequency and pulse width will be delivered using 5 min on and 5 min off stimulation periods during interventional bouts. Every research participant will be slowly acclimated to stimulation. Blood pressure, heart rate, and respiratory rate will be closely monitored throughout stimulation sessions in the Lab by using beat-to-beat blood pressure, and respiratory kinematics monitoring.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Spinal Cord Transcutaneous Stimulation (scTS) group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will undergo 80 RT sessions using standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504). Participants will be trained at the Frazier Rehab Institute and remotely to complete eighty 45-minute sessions during 16 weeks. The participants will be instructed to perform inspiratory and expiratory efforts against a pressure threshold load. The training will be initiated with a load equal to 20% of their individual Maximum Inspiratory Pressure (PImax) and Maximum Expiratory Pressure (PEmax) values with progressive increases as tolerated up to 60% of their baseline PImax and PEmax measures. The goal will be to reach the 60% load of PImax and PEmax during the last week of each month of the training.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will undergo 80 scTS combined with the RT while seated in their own wheelchairs with an approximately 45° head-up tilt. The scTS will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) and Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the RT as described for the Arms 1 and 2.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Transcutaneous spinal cord stimulator</intervention_name>
      <description>Stimulation to the spinal cord will be administered using Neostim/Biostim (Cosyma Inc., Denver CO) device by applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes.</description>
      <arm_group_label>Spinal Cord Transcutaneous Stimulation (scTS) group</arm_group_label>
      <arm_group_label>Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group</arm_group_label>
      <other_name>Non-invasive spinal cord stimulator</other_name>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Respiratory Training</intervention_name>
      <description>Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the respiratory training intervention.</description>
      <arm_group_label>Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group</arm_group_label>
      <arm_group_label>Training (RT) group</arm_group_label>
      <other_name>Respiratory Muscle Training</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  At least 18 years old;&#xD;
  &#xD;
            -  stable medical condition;&#xD;
  &#xD;
            -  no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore&#xD;
               or urinary tract infection that might interfere with respiratory training or&#xD;
               stimulation;&#xD;
  &#xD;
            -  no clinically significant depression, psychiatric disorders or ongoing drug abuse;&#xD;
  &#xD;
            -  non-progressive SCI (no negative change in the neurological level and&#xD;
               motor-completeness assessed during screening when compared to the neurological status&#xD;
               assessed at 6-mo period after injury or at least 6 months prior to the screening),&#xD;
               non-ventilator dependence, motor-complete SCI according to the American Spinal Injury&#xD;
               Association Impairment Scale (AIS) grade &quot;A&quot; or &quot;B&quot; above T5 spinal level;&#xD;
  &#xD;
            -  sustained SCI at least 12 months prior to entering the study;&#xD;
  &#xD;
            -  compared to the normative values for healthy population, at least 15%-deficit in&#xD;
               pulmonary function outcomes (FVC and FEV1) as detected by screening spirometry.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Participants will be excluded from the study if there is a presence of&#xD;
  &#xD;
            -  major pulmonary or cardiovascular disease,&#xD;
  &#xD;
            -  ventilator dependence,&#xD;
  &#xD;
            -  endocrine disorders,&#xD;
  &#xD;
            -  malignancy,&#xD;
  &#xD;
            -  marked obesity,&#xD;
  &#xD;
            -  deep vein thrombosis,&#xD;
  &#xD;
            -  HIV/AIDS-related illness,&#xD;
  &#xD;
            -  secondary hypotension (anemia, hypervolemia, endocrine and neurological diseases),&#xD;
  &#xD;
            -  major esophageal/gastrointestinal problem or other major medical illness&#xD;
               contraindicated for respiratory training or testing.&#xD;
  &#xD;
          During screening, the potential participant will be asked whether she is pregnant or&#xD;
          planning to become pregnant during the study period. Pregnant women are excluded from this&#xD;
          study, as the risk to the fetus is unknown. No pregnancy test or birth control regimen will&#xD;
          be required.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Alexander Ovechkin, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Louisville</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Andrea Willhite, MS</last_name>
      <phone>1-502-581-8675</phone>
      <email>andrea.willhite@louisville.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Frazier Rehabilitation and Neuroscience Institute</name>
        <address>
          <city>Louisville</city>
          <state>Kentucky</state>
          <zip>40202</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrea Willhite, MS</last_name>
        <phone>502-582-8675</phone>
        <email>andrea.willhite@louisville.edu</email>
      </contact>
      <investigator>
        <last_name>Alexander V Ovechkin, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Louisville</investigator_affiliation>
      <investigator_full_name>Alexander V Ovechkin, MD, PhD</investigator_full_name>
      <investigator_title>Assistant Professor, M.D., Ph.D.</investigator_title>
    </responsible_party>
    <keyword>Spinal Cord Injury</keyword>
    <keyword>Respiration</keyword>
    <keyword>Rehabilitation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Respiration Disorders</mesh_term>
      <mesh_term>Spinal Cord Injuries</mesh_term>
      <mesh_term>Wounds and 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/NCT06019949
  org study id: 23.0570
  secondary id: 1R01HL168294
  nct id: NCT06019949
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  Respiratory complications are among the leading causes of death in patients with chronic
        spinal cord injury (SCI). Our previous work showed that pulmonary function can be improved by
        using our original respiratory training method. However, the effectiveness of this
        intervention is limited due to the disruption of brain-spinal connections and consequently
        lowered spinal cord activity below the injury level. Our recent studies showed that
        electrical stimulation of the spinal cord below the level of injury leads to increased
        ventilation which indicates activation of the spinal cord structures related to respiration.
        These findings indicate that spinal cord stimulation can be a promising therapeutic additive
        to the treatment. The goal of this study is to justify the establishment of a new direction
        in rehabilitation for patients with SCI by using a non-invasive spinal cord stimulation in
        combination with respiratory training.
  
        Our aims are: 1) to evaluate the effects of such stimulation applied to the injured spinal
        cord on pulmonary function and respiratory muscle activity, and 2) to evaluate the
        effectiveness and therapeutic mechanisms of the spinal cord stimulation combined with
        respiratory training. Thirty-six individuals with chronic SCI will be recruited and assigned
        to three groups to receive respiratory training or spinal cord stimulation alone or a
        combination of them. All participants will be tested before and after cycles of experimental
        procedures with/or without stimulation. Our hypotheses will be confirmed if the respiratory
        training combined with spinal cord stimulation results in the most enhanced positive effects.
  This is a respiratory rehabilitation-based clinical study consisting of physiologically and
        functionally relevant mapping of respiratory function that enhances our knowledge of
        neurophysiological modulation evoked by non-invasive spinal cord Transcutaneous Stimulation
        (scTS) and contributes to the development of the next generation of rehabilitative
        approaches. Following the screening process and recruiting, the research subjects will
        undergo the following procedures: Subjects (total n=36) will be randomly assigned to three
        groups and will undergo baseline assessments; evaluations before and after 80 sessions of
        specific intervention (Respiratory Training /RT/ alone, scTS alone, or RT in combination with
        scTS); and during 16 week-long follow up period.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Thirty-six SCI participants will be randomly assigned to three groups (n=12 in each group): those who receive RT alone, scTS alone, or a combination of both (scTS+RT).
  After screening and recruitment, primary and secondary outcome measurements will be obtained in the Lab at the following time points: 1) Pre-intervention, after 30-days without any stimulation and/or intervention, 2) Post mapping, (participants with scTS), 3) Post Session #40 (after 8 weeks of intervention), 4) Post Session #80 (after 16 weeks of intervention), and 5) twice during 16-weeks Follow-up Period. In total, it is anticipated that 6 measurements will be obtained for each participant with scTS and 5 measurements for participants without scTS.
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Unidentified data sets will be processed and evaluated by the research staff not directly involved in experimental procedures.
  measure: Maximum Expiratory Pressure (PEmax).
  time frame: Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Standard Spirometry measurement.
  measure: Maximum Inspiratory Pressure (PImax).
  time frame: Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Standard Spirometry measurement.
  measure: Surface electromyography (sEMG) Similarity Index (SI)
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Respiratory multi-muscle activation measures assessed using standard surface electromyography.
  measure: Forced Vital Capacity (FVC).
  time frame: Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Standard Spirometry measurement.
  measure: Forced Expiratory Volume in 1 second (FEV1).
  time frame: Within 2 weeks during screening period; within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Standard Spirometry measurement.
  measure: Baroreflex blood pressure sensitivity (BRS).
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measure of the beat-to-beat blood pressure variability assessed during a Valsalva maneuver.
  measure: Baroreflex heart rate sensitivity (BRS).
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measure of the beat-to-beat heart rate variability assessed during a Valsalva maneuver.
  measure: Baroreflex blood pressure effectiveness index (BEI).
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measure of the beat-to-beat blood pressure variability assessed during a Valsalva maneuver.
  measure: Baroreflex heart rate effectiveness index (BEI).
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measure of the beat-to-beat heart rate variability assessed during a Valsalva maneuver.
  measure: Spinal Cord Independence Measure (SCIM, Version III).
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measures the level of self-care.
  measure: The Craig Handicap Assessment & Reporting Technique (CHART) Questionnaire.
  time frame: Within 4 weeks before an intervention period; within 2 weeks after intervention #40; within 2 weeks after intervention #80; within 2 weeks after 16-weeks and 32-weeks follow-up periods.
  description: Measures the level of handicap in a community setting.
  arm group label: Training (RT) group
  arm group type: Active Comparator
  description: 80 scTS sessions will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) device applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes. During the intervention, optimally configured scTS will be delivered based on the measures assessed during mapping sessions. The scTS with 5 mA-sub-motor threshold intensity with optimal frequency and pulse width will be delivered using 5 min on and 5 min off stimulation periods during interventional bouts. Every research participant will be slowly acclimated to stimulation. Blood pressure, heart rate, and respiratory rate will be closely monitored throughout stimulation sessions in the Lab by using beat-to-beat blood pressure, and respiratory kinematics monitoring.
  arm group label: Spinal Cord Transcutaneous Stimulation (scTS) group
  arm group type: Active Comparator
  description: Participants will undergo 80 RT sessions using standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504). Participants will be trained at the Frazier Rehab Institute and remotely to complete eighty 45-minute sessions during 16 weeks. The participants will be instructed to perform inspiratory and expiratory efforts against a pressure threshold load. The training will be initiated with a load equal to 20% of their individual Maximum Inspiratory Pressure (PImax) and Maximum Expiratory Pressure (PEmax) values with progressive increases as tolerated up to 60% of their baseline PImax and PEmax measures. The goal will be to reach the 60% load of PImax and PEmax during the last week of each month of the training.
  arm group label: Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group
  arm group type: Experimental
  description: Participants will undergo 80 scTS combined with the RT while seated in their own wheelchairs with an approximately 45° head-up tilt. The scTS will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) and Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the RT as described for the Arms 1 and 2.
  intervention type: Device
  intervention name: Transcutaneous spinal cord stimulator
  description: Stimulation to the spinal cord will be administered using Neostim/Biostim (Cosyma Inc., Denver CO) device by applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes.
  arm group label: Spinal Cord Transcutaneous Stimulation (scTS) group
  arm group label: Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group
  other name: Non-invasive spinal cord stimulator
  intervention type: Device
  intervention name: Respiratory Training
  description: Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the respiratory training intervention.
  arm group label: Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group
  arm group label: Training (RT) group
  other name: Respiratory Muscle Training
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Alexander Ovechkin, MD, PhD
  role: Principal Investigator
  affiliation: University of Louisville
  last name: Andrea Willhite, MS
  phone: 1-502-581-8675
  email: andrea.willhite@louisville.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Louisville
  investigator full name: Alexander V Ovechkin, MD, PhD
  investigator title: Assistant Professor, M.D., Ph.D.
  mesh term: Respiration Disorders
  mesh term: Spinal Cord Injuries
  mesh term: Wounds and Injuries
  sharing ipd: No