<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/NCT02240329</url>
  </required_header>
  <id_info>
    <org_study_id>217-2012</org_study_id>
    <nct_id>NCT02240329</nct_id>
  </id_info>
  <brief_title>Assessment of Dystussia in Traumatic Brain Injury</brief_title>
  <official_title>Assessment of Dystussia in Traumatic Brain 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>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to evaluate coughing in people who have had a brain&#xD;
      injury. It is hypothesized that individuals who have sustained a brain injury will&#xD;
      demonstrate differences in cough waveform and respiratory measures compared to individuals&#xD;
      who have not sustained a brain injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recovery of people with mild, moderate, or severe swallowing, speech, hearing, and&#xD;
      cognitive-communication impairments is best facilitated by a team of multidisciplinary&#xD;
      specialists. Symptoms associated with traumatic brain injury (TBI) include disordered&#xD;
      swallowing (dysphagia), ataxia and, frequently, but not inevitably, dysarthria or disorder of&#xD;
      speech. Airway compromise also exists in the form of impaired cough, or dystussia. In view of&#xD;
      the frequency of oral intake problems in individuals with TBI and the presence of weakened&#xD;
      cough, or absence of cough, along with the added challenge of the cognitive-communicative&#xD;
      problems, further studies are needed to increase our understanding of the degree of&#xD;
      disordered airway protection. From this work appropriate intervention strategies can be&#xD;
      designed along with an understanding of the compensations that may be used to assist with&#xD;
      improving swallow and airway safety, oral intake and management.&#xD;
&#xD;
      Informed Consent Process:&#xD;
&#xD;
      Investigators working with subjects with TBI, and who are also aware of this study, will have&#xD;
      the ability to provide potential participants with a business card containing only the name&#xD;
      of the study coordinator (Dr. Erin Silverman) as well as her email and telephone numbers. The&#xD;
      individual participants will be responsible for contacting Dr. Silverman if they wish to&#xD;
      participate. Additional participants will be recruited via face to face methods and by the&#xD;
      previously IRB-approved study flyer at local brain injury support groups and Shands&#xD;
      Rehabilitation Hospital.The staff member consenting (Dr. Silverman) has completed University&#xD;
      of Florida training on HIPAA and privacy issues. Subjects do not have to give an immediate&#xD;
      response about enrolling and may freely discuss the study with people of their choice before&#xD;
      making a decision. Capacity to consent will be decided by the consenting staff member (Dr.&#xD;
      Silverman). The study will be explained to the subject, any questions answered, and a written&#xD;
      and signed consent completed along with a HIPAA authorization. Written consent will be&#xD;
      obtained prior to collection of any health history or study data. Once written informed&#xD;
      consent is obtained, Dr. Silverman will conduct an extensive interview in order to insure the&#xD;
      subject meets all required inclusionary/exclusionary criteria.&#xD;
&#xD;
      Neuropsychological Testing: The MOCA (Montreal Cognitive Assessment) will be administered by&#xD;
      Dr. Silverman, on each participant, upon entry into the study.&#xD;
&#xD;
      Measures of TBI severity: Multiple studies have correlated severity of TBI upon initial&#xD;
      admission related to the TBI with swallowing function. The Glasgow Coma Scale (GCS) and&#xD;
      Rancho Los Amigos Scale (RLAS) are commonly administered upon admission of TBI patients. When&#xD;
      available (availability may vary depending on the hospital at initial admission) we will&#xD;
      record the GCS and/or RLAS scores from admission. As well, the investigators will administer&#xD;
      the RLAS upon enrollment in the study. These measures will be incorporated into our&#xD;
      statistical model to better understand the heterogeneity of cognitive impairment on swallow&#xD;
      and cough function.&#xD;
&#xD;
      Cough and respiratory measures: Pulmonary status screening measures: The forced expired&#xD;
      volume in the first second (FEV1) of a forced vital capacity (FVC) exhalation are measures&#xD;
      used to screen pulmonary function (American Thoracic Society). Spirometry is used to derive&#xD;
      FVC, FEV1 and the ratio FEV1/FVC measures (Spirovision 3+m, Futuremed). Alternatively, if the&#xD;
      subject is unable to perform the cognitive voluntary spirometric task, upper airway&#xD;
      respiratory resistance will be measured with impulse oscillometry (lOS, Jaeger Instruments).&#xD;
&#xD;
      Maximum Respiratory Pressures: Maximum inspiratory and expiratory pressures are an indirect&#xD;
      measure of inspiratory and expiratory muscle strength, respectively. The ability to generate&#xD;
      high expiratory airflows is essential to producing high expiratory airflow, and subsequently&#xD;
      cough production and will be measured at the initial assessment in all studies.&#xD;
&#xD;
      Cough: The participant will be instrumented for the measurement of the respiratory airflow&#xD;
      pattern during spontaneous breathing, voluntary cough and reflex capsaicin induced cough. A&#xD;
      facemask with a pneumotachograph will be used to record the airflow changes associated with&#xD;
      spontaneous breathing and cough. The mouth airflow signal will be digitized and recorded on a&#xD;
      desktop computer (Chart, ADinstruments, Inc). Inspiratory and expiratory muscle EMG will be&#xD;
      recorded to provide a neuromuscular motor assessment of cough strength. The computer signals&#xD;
      will be analyzed to determine inspiratory breath phase, expiratory breath phase, inspiratory&#xD;
      cough phase, cough compression phase, and expiratory cough phase. Because it has been&#xD;
      reported that brain injury differentially affects the neuromuscular motor pattern of&#xD;
      voluntary and reflex elicited coughs, it is essential to elicit coughs with both peripheral&#xD;
      afferent stimulation (capsaicin; reflexive cough) and voluntary induced cough in these TBI&#xD;
      participants.&#xD;
&#xD;
      Capsaicin administration: After the participant is instrumented with the facemask, he/she&#xD;
      will be seated comfortably in a chair in front of an airflow fume hood. The airflow fume hood&#xD;
      prevents exposure of the participant and experimenter to the nebulized solution except when&#xD;
      the participant inhales for the capsaicin challenge. Participants will inspire deeply through&#xD;
      the nebulizer (containing the capsaicin or a vehicle solution) coupled to the facemask and&#xD;
      pneumotachograph. The outflow nebulizer gas will be passed through an isopropyl alcohol&#xD;
      solution to remove capsaicin from the air vented into the fume hood. Cough threshold and&#xD;
      sensitivity will be determined using our established randomized block presentation method of&#xD;
      graded capsaicin concentrations (0-2001-JM). The investigators have an FDA IND # 76866 for&#xD;
      the use of capsaicin in the study of cough motor pattern. This will take 10-15 minutes to&#xD;
      complete.&#xD;
&#xD;
      Design and Procedures: This project will address the Specific Aim over a 1-year time period.&#xD;
      Our Specific Aim will focus on characterizing the mechanical features of swallow and cough&#xD;
      motor function in subjects with TBI and the swallow and cough reconfiguration of respiratory&#xD;
      pattern. Our Specific Aim will allow us to determine the relationship between TBI and both&#xD;
      swallow and cough dysfunction.&#xD;
&#xD;
      Study Protocol: Subjects with a medical history of TBI will be recruited from community TBI&#xD;
      support groups and through face to face recruitment procedures. Once informed consent has&#xD;
      been obtained, relevant medical history will be reviewed, and the participants will complete&#xD;
      screening procedures to determine inclusionary/exclusionary criteria. If inclusionary and&#xD;
      exclusionary criteria are met, participants will complete the following tests:&#xD;
&#xD;
        -  MIP and MEP measurement&#xD;
&#xD;
        -  Reflex and voluntary cough assessments&#xD;
&#xD;
      Timeframe: This is a one-time visit study. Therefore, participants will be followed only on&#xD;
      the day they present for study procedures. There will be no follow up beyond this day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Early Phase 1</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration</measure>
    <time_frame>Day 1</time_frame>
    <description>Following 30 seconds of tidal breathing (to allow for acclimation to the facemask), participants were instructed to &quot;take a sharp breath in&quot; whereupon the nebulized capsaicin solution was automatically administered by the dosimeter. Following each aerosol presentation, the participant was instructed to rate their UTC using a modified Borg Rating Scale where 1 = no UTC and 10 = maximum UTC. Between presentations, participants were given a minimum of a one-minute rest period where they were offered water. An average across all measurements was performed for the analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Coughs in Response to Stimulation With 200 Micro Moles Capsaicin in Solution</measure>
    <time_frame>Day 1</time_frame>
    <description>The total cough count (CTot) was determined by counting all cough events that occurred following each presentation of capsaicin solution. CTot was made, in real time, by two investigators and confirmed via review of the recorded cough airflow signal. Capsaicin concentration necessary to elicit a two cough threshold response (C2) within 30 seconds of presentation, on at least two (out of three) trials of that concentration, was identified from the cough count record. An average across all measurements was performed for the analysis.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>TBI</condition>
  <condition>Brain Injury</condition>
  <arm_group>
    <arm_group_label>Individuals with TBI</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Neuropsychological Testing and Measures of TBI severity</intervention_name>
    <description>A brief cognitive assessment will be given to each participant when he or she presents for this project.</description>
    <arm_group_label>Individuals with TBI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Respiratory measures</intervention_name>
    <description>We will collect measures of cough airflow and breathing strength.</description>
    <arm_group_label>Individuals with TBI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capsaicin cough sensitivity testing</intervention_name>
    <description>Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
    <arm_group_label>Individuals with TBI</arm_group_label>
    <other_name>Cough reflex testing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. TBI within 5 years - may have accompanying neck injury but not extensive&#xD;
             reconstruction of oral structures.&#xD;
&#xD;
          2. Pulmonary function screening: FEV1 &gt;75%, FVC &gt; 75% and FEV1/FVC ratio of &gt;75% of age,&#xD;
             sex and ethnicity corrected predicted values, impulse oscillometry R5 resistance&#xD;
             measurement within 15% of age, sex and ethnicity corrected predicted values.&#xD;
&#xD;
          3. Medical status permits participation.&#xD;
&#xD;
          4. Cognitive status permits participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Refuses consent.&#xD;
&#xD;
          2. Cognitively incapable of informed consent&#xD;
&#xD;
          3. Active substance dependence/use (from clinical interview/record review)&#xD;
&#xD;
          4. Diagnosis of moderate to very severe chronic obstructive pulmonary disease (COPD; from&#xD;
             patient interview)&#xD;
&#xD;
          5. History of chronic cough and/or cough syncope (From clinical interview)&#xD;
&#xD;
          6. History of cancer in the head or neck (From clinical interview)&#xD;
&#xD;
          7. History of radiation to the head or neck (From clinical interview)&#xD;
&#xD;
          8. History of stroke or other neurodegenerative disease (From clinical interview)&#xD;
             Participants will be enrolled without regard for sex, ethnicity, or age.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul W Davenport, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>June 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <results_first_submitted>August 10, 2015</results_first_submitted>
  <results_first_submitted_qc>September 29, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 28, 2015</results_first_posted>
  <last_update_submitted>September 29, 2015</last_update_submitted>
  <last_update_submitted_qc>September 29, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 28, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>respiratory</keyword>
  <keyword>cough</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capsaicin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Individuals With TBI</title>
          <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.&#xD;
Neuropsychological Testing and Measures of TBI severity: A brief cognitive assessment will be given to each participant when he or she presents for this project.&#xD;
Respiratory measures: We will collect measures of cough airflow and breathing strength.&#xD;
Capsaicin cough sensitivity testing: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Determination of Urge to Cough</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Individuals With TBI</title>
          <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.&#xD;
Neuropsychological Testing and Measures of TBI severity: A brief cognitive assessment will be given to each participant when he or she presents for this project.&#xD;
Respiratory measures: We will collect measures of cough airflow and breathing strength.&#xD;
Capsaicin cough sensitivity testing: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.38" spread="13.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration</title>
        <description>Following 30 seconds of tidal breathing (to allow for acclimation to the facemask), participants were instructed to &quot;take a sharp breath in&quot; whereupon the nebulized capsaicin solution was automatically administered by the dosimeter. Following each aerosol presentation, the participant was instructed to rate their UTC using a modified Borg Rating Scale where 1 = no UTC and 10 = maximum UTC. Between presentations, participants were given a minimum of a one-minute rest period where they were offered water. An average across all measurements was performed for the analysis.</description>
        <time_frame>Day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Individuals With TBI</title>
            <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.&#xD;
Neuropsychological Testing and Measures of TBI severity: A brief cognitive assessment will be given to each participant when he or she presents for this project.&#xD;
Respiratory measures: We will collect measures of cough airflow and breathing strength.&#xD;
Capsaicin cough sensitivity testing: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
          </group>
        </group_list>
        <measure>
          <title>Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration</title>
          <description>Following 30 seconds of tidal breathing (to allow for acclimation to the facemask), participants were instructed to &quot;take a sharp breath in&quot; whereupon the nebulized capsaicin solution was automatically administered by the dosimeter. Following each aerosol presentation, the participant was instructed to rate their UTC using a modified Borg Rating Scale where 1 = no UTC and 10 = maximum UTC. Between presentations, participants were given a minimum of a one-minute rest period where they were offered water. An average across all measurements was performed for the analysis.</description>
          <units>Units on a Borg scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Coughs in Response to Stimulation With 200 Micro Moles Capsaicin in Solution</title>
        <description>The total cough count (CTot) was determined by counting all cough events that occurred following each presentation of capsaicin solution. CTot was made, in real time, by two investigators and confirmed via review of the recorded cough airflow signal. Capsaicin concentration necessary to elicit a two cough threshold response (C2) within 30 seconds of presentation, on at least two (out of three) trials of that concentration, was identified from the cough count record. An average across all measurements was performed for the analysis.</description>
        <time_frame>Day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Individuals With TBI</title>
            <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.&#xD;
Neuropsychological Testing and Measures of TBI severity: A brief cognitive assessment will be given to each participant when he or she presents for this project.&#xD;
Respiratory measures: We will collect measures of cough airflow and breathing strength.&#xD;
Capsaicin cough sensitivity testing: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Coughs in Response to Stimulation With 200 Micro Moles Capsaicin in Solution</title>
          <description>The total cough count (CTot) was determined by counting all cough events that occurred following each presentation of capsaicin solution. CTot was made, in real time, by two investigators and confirmed via review of the recorded cough airflow signal. Capsaicin concentration necessary to elicit a two cough threshold response (C2) within 30 seconds of presentation, on at least two (out of three) trials of that concentration, was identified from the cough count record. An average across all measurements was performed for the analysis.</description>
          <units>cough events following stimulation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.83" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Duration of study (one day)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Individuals With TBI</title>
          <description>Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.&#xD;
Neuropsychological Testing and Measures of TBI severity: A brief cognitive assessment will be given to each participant when he or she presents for this project.&#xD;
Respiratory measures: We will collect measures of cough airflow and breathing strength.&#xD;
Capsaicin cough sensitivity testing: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Erin Pearson Ph.D CCC/SLP</name_or_title>
      <organization>University of Florida</organization>
      <phone>352-339-4100</phone>
      <email>epearson@ufl.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02240329
org study id: 217-2012
nct id: NCT02240329
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this research study is to evaluate coughing in people who have had a brain
      injury. It is hypothesized that individuals who have sustained a brain injury will
      demonstrate differences in cough waveform and respiratory measures compared to individuals
      who have not sustained a brain injury.
Recovery of people with mild, moderate, or severe swallowing, speech, hearing, and
      cognitive-communication impairments is best facilitated by a team of multidisciplinary
      specialists. Symptoms associated with traumatic brain injury (TBI) include disordered
      swallowing (dysphagia), ataxia and, frequently, but not inevitably, dysarthria or disorder of
      speech. Airway compromise also exists in the form of impaired cough, or dystussia. In view of
      the frequency of oral intake problems in individuals with TBI and the presence of weakened
      cough, or absence of cough, along with the added challenge of the cognitive-communicative
      problems, further studies are needed to increase our understanding of the degree of
      disordered airway protection. From this work appropriate intervention strategies can be
      designed along with an understanding of the compensations that may be used to assist with
      improving swallow and airway safety, oral intake and management.

      Informed Consent Process:

      Investigators working with subjects with TBI, and who are also aware of this study, will have
      the ability to provide potential participants with a business card containing only the name
      of the study coordinator (Dr. Erin Silverman) as well as her email and telephone numbers. The
      individual participants will be responsible for contacting Dr. Silverman if they wish to
      participate. Additional participants will be recruited via face to face methods and by the
      previously IRB-approved study flyer at local brain injury support groups and Shands
      Rehabilitation Hospital.The staff member consenting (Dr. Silverman) has completed University
      of Florida training on HIPAA and privacy issues. Subjects do not have to give an immediate
      response about enrolling and may freely discuss the study with people of their choice before
      making a decision. Capacity to consent will be decided by the consenting staff member (Dr.
      Silverman). The study will be explained to the subject, any questions answered, and a written
      and signed consent completed along with a HIPAA authorization. Written consent will be
      obtained prior to collection of any health history or study data. Once written informed
      consent is obtained, Dr. Silverman will conduct an extensive interview in order to insure the
      subject meets all required inclusionary/exclusionary criteria.

      Neuropsychological Testing: The MOCA (Montreal Cognitive Assessment) will be administered by
      Dr. Silverman, on each participant, upon entry into the study.

      Measures of TBI severity: Multiple studies have correlated severity of TBI upon initial
      admission related to the TBI with swallowing function. The Glasgow Coma Scale (GCS) and
      Rancho Los Amigos Scale (RLAS) are commonly administered upon admission of TBI patients. When
      available (availability may vary depending on the hospital at initial admission) we will
      record the GCS and/or RLAS scores from admission. As well, the investigators will administer
      the RLAS upon enrollment in the study. These measures will be incorporated into our
      statistical model to better understand the heterogeneity of cognitive impairment on swallow
      and cough function.

      Cough and respiratory measures: Pulmonary status screening measures: The forced expired
      volume in the first second (FEV1) of a forced vital capacity (FVC) exhalation are measures
      used to screen pulmonary function (American Thoracic Society). Spirometry is used to derive
      FVC, FEV1 and the ratio FEV1/FVC measures (Spirovision 3+m, Futuremed). Alternatively, if the
      subject is unable to perform the cognitive voluntary spirometric task, upper airway
      respiratory resistance will be measured with impulse oscillometry (lOS, Jaeger Instruments).

      Maximum Respiratory Pressures: Maximum inspiratory and expiratory pressures are an indirect
      measure of inspiratory and expiratory muscle strength, respectively. The ability to generate
      high expiratory airflows is essential to producing high expiratory airflow, and subsequently
      cough production and will be measured at the initial assessment in all studies.

      Cough: The participant will be instrumented for the measurement of the respiratory airflow
      pattern during spontaneous breathing, voluntary cough and reflex capsaicin induced cough. A
      facemask with a pneumotachograph will be used to record the airflow changes associated with
      spontaneous breathing and cough. The mouth airflow signal will be digitized and recorded on a
      desktop computer (Chart, ADinstruments, Inc). Inspiratory and expiratory muscle EMG will be
      recorded to provide a neuromuscular motor assessment of cough strength. The computer signals
      will be analyzed to determine inspiratory breath phase, expiratory breath phase, inspiratory
      cough phase, cough compression phase, and expiratory cough phase. Because it has been
      reported that brain injury differentially affects the neuromuscular motor pattern of
      voluntary and reflex elicited coughs, it is essential to elicit coughs with both peripheral
      afferent stimulation (capsaicin; reflexive cough) and voluntary induced cough in these TBI
      participants.

      Capsaicin administration: After the participant is instrumented with the facemask, he/she
      will be seated comfortably in a chair in front of an airflow fume hood. The airflow fume hood
      prevents exposure of the participant and experimenter to the nebulized solution except when
      the participant inhales for the capsaicin challenge. Participants will inspire deeply through
      the nebulizer (containing the capsaicin or a vehicle solution) coupled to the facemask and
      pneumotachograph. The outflow nebulizer gas will be passed through an isopropyl alcohol
      solution to remove capsaicin from the air vented into the fume hood. Cough threshold and
      sensitivity will be determined using our established randomized block presentation method of
      graded capsaicin concentrations (0-2001-JM). The investigators have an FDA IND # 76866 for
      the use of capsaicin in the study of cough motor pattern. This will take 10-15 minutes to
      complete.

      Design and Procedures: This project will address the Specific Aim over a 1-year time period.
      Our Specific Aim will focus on characterizing the mechanical features of swallow and cough
      motor function in subjects with TBI and the swallow and cough reconfiguration of respiratory
      pattern. Our Specific Aim will allow us to determine the relationship between TBI and both
      swallow and cough dysfunction.

      Study Protocol: Subjects with a medical history of TBI will be recruited from community TBI
      support groups and through face to face recruitment procedures. Once informed consent has
      been obtained, relevant medical history will be reviewed, and the participants will complete
      screening procedures to determine inclusionary/exclusionary criteria. If inclusionary and
      exclusionary criteria are met, participants will complete the following tests:

        -  MIP and MEP measurement

        -  Reflex and voluntary cough assessments

      Timeframe: This is a one-time visit study. Therefore, participants will be followed only on
      the day they present for study procedures. There will be no follow up beyond this day.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Average Urge to Cough (UTC) Following Administration of 200 Micro Mole Capsaicin Solution Concentration
time frame: Day 1
description: Following 30 seconds of tidal breathing (to allow for acclimation to the facemask), participants were instructed to "take a sharp breath in" whereupon the nebulized capsaicin solution was automatically administered by the dosimeter. Following each aerosol presentation, the participant was instructed to rate their UTC using a modified Borg Rating Scale where 1 = no UTC and 10 = maximum UTC. Between presentations, participants were given a minimum of a one-minute rest period where they were offered water. An average across all measurements was performed for the analysis.
measure: Number of Coughs in Response to Stimulation With 200 Micro Moles Capsaicin in Solution
time frame: Day 1
description: The total cough count (CTot) was determined by counting all cough events that occurred following each presentation of capsaicin solution. CTot was made, in real time, by two investigators and confirmed via review of the recorded cough airflow signal. Capsaicin concentration necessary to elicit a two cough threshold response (C2) within 30 seconds of presentation, on at least two (out of three) trials of that concentration, was identified from the cough count record. An average across all measurements was performed for the analysis.
arm group label: Individuals with TBI
arm group type: Other
description: Individuals who have sustained a traumatic brain injury during the previous five years. Will have the following tests performed: Neuropsychological Testing and Measures of TBI severity; Cough and respiratory measures (including Maximum Respiratory Pressures); and Capsaicin cough sensitivity testing.
intervention type: Behavioral
intervention name: Neuropsychological Testing and Measures of TBI severity
description: A brief cognitive assessment will be given to each participant when he or she presents for this project.
arm group label: Individuals with TBI
intervention type: Behavioral
intervention name: Respiratory measures
description: We will collect measures of cough airflow and breathing strength.
arm group label: Individuals with TBI
intervention type: Drug
intervention name: Capsaicin cough sensitivity testing
description: Subjects will inhale a saline vapor mixed with various concentrations of capsaicin powder in order to determine how sensitive his or her cough response is.
arm group label: Individuals with TBI
other name: Cough reflex testing
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Paul W Davenport, Ph.D.
role: Principal Investigator
affiliation: University of Florida
facility: 
country: United States
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries
mesh term: Capsaicin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 