<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/NCT01728974</url>
  </required_header>
  <id_info>
    <org_study_id>2012P000957A</org_study_id>
    <secondary_id>1R01HL102321-01A1</secondary_id>
    <nct_id>NCT01728974</nct_id>
  </id_info>
  <brief_title>Mechanisms of Pharyngeal Collapse in Sleep Apnea, Study A</brief_title>
  <official_title>Mechanisms of Pharyngeal Collapse in Sleep Apnea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</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>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In obstructive sleep apnea, the upper airway recurrently closes during sleep. The mechanisms&#xD;
      that lead to airway closure are not completely understood. While the airway of some people&#xD;
      narrows and airflow decreases during inspiration due to increasing inspiratory effort, others&#xD;
      maintain constant airflow throughout inspiration. Airway neuromuscular reflexes may protect&#xD;
      against airway narrowing that occurs due to increasing inspiratory effort. To test this&#xD;
      hypothesis, the investigators will initially measure airway neuromuscular reflex and&#xD;
      inspiratory flow and then attenuate neuromuscular reflex through topical pharyngeal&#xD;
      anesthesia to observe the effects on inspiratory flow.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The mechanisms that lead to airway closure are not completely understood. While the airway of&#xD;
      some people narrows and airflow decreases during inspiration due to increasing inspiratory&#xD;
      effort, others maintain constant airflow throughout inspiration (negative effort dependence,&#xD;
      NED). The investigators hypothesize that upper airway neuromuscular reflexes may protect&#xD;
      against narrowing that occurs due to increasing inspiratory effort. Topical oropharyngeal&#xD;
      anesthesia has been shown to reduce neuromuscular reflexes. Thus, the investigators also&#xD;
      hypothesize that patients with stable inspiratory flow will develop NED once the reflexes&#xD;
      have been impaired with topical anesthetic. The investigators plan to:&#xD;
&#xD;
        1. measure upper airway muscle EMG to assess how it corresponds to the presence or absence&#xD;
           of NED. This aim will allow us to test the hypothesis that robust upper airway muscle&#xD;
           reflexes can protect against NED.&#xD;
&#xD;
        2. reduce upper airway muscle activity and reflexes by topical oropharyngeal anesthesia.&#xD;
           This will allow us to test the hypothesis that attenuated upper airway muscle activity&#xD;
           induced by topical anesthesia can induce NED.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 8, 2012</start_date>
  <completion_date type="Actual">December 26, 2018</completion_date>
  <primary_completion_date type="Actual">December 26, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Negative effort dependence variation</measure>
    <time_frame>After pharyngeal topical anesthesia</time_frame>
    <description>The magnitude of negative effort dependence will be expressed as the percent decrease in inspiratory flow from Vmax. NED will be compared before and after topical upper airway anesthesia</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <condition>Pathophysiology</condition>
  <arm_group>
    <arm_group_label>Pharyngeal topical anesthesia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pharyngeal topical anesthesia will be performed using 4% lidocaine spray</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharyngeal topical anesthesia</intervention_name>
    <description>Pharyngeal topical anesthesia will be performed using 4% lidocaine spray</description>
    <arm_group_label>Pharyngeal topical anesthesia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normal subjects or patients with OSA&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any unstable cardiac condition (other than well controlled hypertension) or pulmonary&#xD;
             problems.&#xD;
&#xD;
          -  Any medication known to influence breathing, sleep/arousal or muscle physiology&#xD;
&#xD;
          -  Concurrent sleep disorders (insomnia, narcolepsy, central sleep apnea or parasomnia)&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Inability to sleep supine&#xD;
&#xD;
          -  Allergy to lidocaine or oxymetazoline HCl&#xD;
&#xD;
          -  For women: Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David A Wellman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>July 9, 2019</last_update_submitted>
  <last_update_submitted_qc>July 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>David Andrew Wellman</investigator_full_name>
    <investigator_title>Andrew Wellman</investigator_title>
  </responsible_party>
  <keyword>Obstructive Sleep Apnea</keyword>
  <keyword>Pathophysiology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01728974
org study id: 2012P000957A
secondary id: 1R01HL102321-01A1
nct id: NCT01728974
lead sponsor: 
collaborator: 
has dmc: No
In obstructive sleep apnea, the upper airway recurrently closes during sleep. The mechanisms
      that lead to airway closure are not completely understood. While the airway of some people
      narrows and airflow decreases during inspiration due to increasing inspiratory effort, others
      maintain constant airflow throughout inspiration. Airway neuromuscular reflexes may protect
      against airway narrowing that occurs due to increasing inspiratory effort. To test this
      hypothesis, the investigators will initially measure airway neuromuscular reflex and
      inspiratory flow and then attenuate neuromuscular reflex through topical pharyngeal
      anesthesia to observe the effects on inspiratory flow.
The mechanisms that lead to airway closure are not completely understood. While the airway of
      some people narrows and airflow decreases during inspiration due to increasing inspiratory
      effort, others maintain constant airflow throughout inspiration (negative effort dependence,
      NED). The investigators hypothesize that upper airway neuromuscular reflexes may protect
      against narrowing that occurs due to increasing inspiratory effort. Topical oropharyngeal
      anesthesia has been shown to reduce neuromuscular reflexes. Thus, the investigators also
      hypothesize that patients with stable inspiratory flow will develop NED once the reflexes
      have been impaired with topical anesthetic. The investigators plan to:

        1. measure upper airway muscle EMG to assess how it corresponds to the presence or absence
           of NED. This aim will allow us to test the hypothesis that robust upper airway muscle
           reflexes can protect against NED.

        2. reduce upper airway muscle activity and reflexes by topical oropharyngeal anesthesia.
           This will allow us to test the hypothesis that attenuated upper airway muscle activity
           induced by topical anesthesia can induce NED.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Negative effort dependence variation
time frame: After pharyngeal topical anesthesia
description: The magnitude of negative effort dependence will be expressed as the percent decrease in inspiratory flow from Vmax. NED will be compared before and after topical upper airway anesthesia
arm group label: Pharyngeal topical anesthesia
arm group type: Experimental
description: Pharyngeal topical anesthesia will be performed using 4% lidocaine spray
intervention type: Other
intervention name: Pharyngeal topical anesthesia
description: Pharyngeal topical anesthesia will be performed using 4% lidocaine spray
arm group label: Pharyngeal topical anesthesia
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David A Wellman
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: David Andrew Wellman
investigator title: Andrew Wellman
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Anesthetics