<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/NCT03235466</url>
  </required_header>
  <id_info>
    <org_study_id>181207</org_study_id>
    <nct_id>NCT03235466</nct_id>
  </id_info>
  <brief_title>A Prospective Trial of Behavioral Therapy for Chronic Cough</brief_title>
  <official_title>A Prospective Trial of Behavioral Therapy for Chronic Cough</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study seeks to explore whether heart rate variability (HRV) biofeedback can be effective&#xD;
      in the treatment of chronic cough. Chronic cough has many causes, including asthma, postnasal&#xD;
      drip, and gastroesophageal reflux disease (GERD), each with a specific treatment. However,&#xD;
      among a subset of cough patients, no clear cause is found despite extensive workup, and&#xD;
      traditional treatment methods do not provide relief. Several studies revealed less common&#xD;
      causes of chronic cough and disordered breathing such as vagal neuropathy, paradoxical vocal&#xD;
      fold motion, and stress. Additional research identified links between the neurological&#xD;
      networks that produce the cough reflex and those that maintain normal breathing. HRV&#xD;
      biofeedback is a self-regulation technique that uses computer equipment to monitor heart rate&#xD;
      and breathing, two key functions of the autonomic nervous system. By using this non-invasive&#xD;
      behavioral technique, cough patients can regulate their breathing and autonomic function,&#xD;
      potentially leading to improved autonomic balance and a reduction in cough symptoms.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2021</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>Randomized controlled trial of 3 groups: 1) standard voice therapy 2) voice therapy and heart rate variability biofeedback and 3) heart rate variability biofeedback</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Cough reduction</measure>
    <time_frame>3 weeks</time_frame>
    <description>Measured by changes in cough severity index and patient recordings</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Durability of cough remediation</measure>
    <time_frame>8 weeks</time_frame>
    <description>Phone call to patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in dyspnea</measure>
    <time_frame>3 weeks</time_frame>
    <description>Measured by dyspnea index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in voice</measure>
    <time_frame>3 weeks</time_frame>
    <description>Measured by voice handicap index</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Cough</condition>
  <arm_group>
    <arm_group_label>Voice Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(Group 1) will undergo active training in behavioral cough suppression and laryngeal relaxation exercises, but will not receive HRVB. Traditional cough suppression and laryngeal relaxation exercises include pursed lip breathing, swallowing (water, lozenge, gum, ice chips), sustained semi-occluded voicing, discussion and mitigation of triggers, maintaining a cough journal, addressing muscle tension dysphonia if indicated, and developing prophylaxis suppression and laryngeal relaxation based on stimulability. Participants in Group 1 will receive handwritten guidance indicating exercises to practice at home.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Voice Therapy and Heart Rate Variability Biofeedback</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Voice therapy as described in Arm 1. HRVB involves measure respiratory rate, heart rate, body temperature and skin conductance. Participants are guided through reduced breathing rate until a resonant frequency is attained. HRVB breathing simulates resonance between the baroreflex rhythm and respiration based rhythm, increasing heart rate variability and baroreceptor sensitivity. Evidence suggests HRVB improves autonomic regularity. We propose this novel modality to address centrally regulated hypersensitivity that perpetuates coughing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Heart Rate Variability Biofeedback</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HRVB as indicated in Arm 2. No instruction will be provided for cough suppression, laryngeal desensitization, voice tasks or hygiene that traditionally reduces cough frequency and severity. This is the experimental arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Voice Therapy</intervention_name>
    <description>See Arm 1 &amp; 2</description>
    <arm_group_label>Voice Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Voice Therapy and Heart Rate Variability Biofeedback</intervention_name>
    <description>See Arm 2 &amp; 3</description>
    <arm_group_label>Voice Therapy and Heart Rate Variability Biofeedback</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Heart Rate Variability Biofeedback</intervention_name>
    <description>See Arm 2 &amp; 3</description>
    <arm_group_label>Heart Rate Variability Biofeedback</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  8+ weeks of cough, Fluent English speaker, Have access to an electronic mobile device&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On neuromodulator therapy, cardiac arrhythmia, dysphagia, prior HRVB or mindfulness,&#xD;
             head and neck surgery of the oropharynx, neck or larynx, lung surgery, pulmonary&#xD;
             pathology other than asthma, tourette syndrome, ACE inhibitor use, current or recent&#xD;
             smoker.&#xD;
&#xD;
        Added exclusion criteria as of March 2020 - history of COVID+.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Philip Weissbrod, MD</last_name>
    <phone>858-657-8590</phone>
    <email>pweissbrod@ucsd.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Erin Walsh, MA</last_name>
    <phone>858-657-8590</phone>
    <email>ehwalsh@ucsd.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCSD Center for Voice and Swallowing</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92122</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philip Weissbrod, MD</last_name>
      <phone>858-657-8590</phone>
      <email>pweissbrod@ucsd.edu</email>
    </contact>
    <contact_backup>
      <last_name>Erin Walsh, MA</last_name>
      <phone>8586578590</phone>
      <email>ehwalsh@ucsd.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 15, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>December 3, 2020</last_update_submitted>
  <last_update_submitted_qc>December 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Philip Weissbrod</investigator_full_name>
    <investigator_title>Director, Center for Voice and Swallowing</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cough</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>July 4, 2022</submitted>
    <returned>May 12, 2023</returned>
  </pending_results>
  <!-- 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/NCT03235466
org study id: 181207
nct id: NCT03235466
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study seeks to explore whether heart rate variability (HRV) biofeedback can be effective
      in the treatment of chronic cough. Chronic cough has many causes, including asthma, postnasal
      drip, and gastroesophageal reflux disease (GERD), each with a specific treatment. However,
      among a subset of cough patients, no clear cause is found despite extensive workup, and
      traditional treatment methods do not provide relief. Several studies revealed less common
      causes of chronic cough and disordered breathing such as vagal neuropathy, paradoxical vocal
      fold motion, and stress. Additional research identified links between the neurological
      networks that produce the cough reflex and those that maintain normal breathing. HRV
      biofeedback is a self-regulation technique that uses computer equipment to monitor heart rate
      and breathing, two key functions of the autonomic nervous system. By using this non-invasive
      behavioral technique, cough patients can regulate their breathing and autonomic function,
      potentially leading to improved autonomic balance and a reduction in cough symptoms.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial of 3 groups: 1) standard voice therapy 2) voice therapy and heart rate variability biofeedback and 3) heart rate variability biofeedback
primary purpose: Treatment
masking: Single (Participant)
measure: Percentage of Cough reduction
time frame: 3 weeks
description: Measured by changes in cough severity index and patient recordings
measure: Durability of cough remediation
time frame: 8 weeks
description: Phone call to patients
measure: Changes in dyspnea
time frame: 3 weeks
description: Measured by dyspnea index
measure: Change in voice
time frame: 3 weeks
description: Measured by voice handicap index
arm group label: Voice Therapy
arm group type: Active Comparator
description: (Group 1) will undergo active training in behavioral cough suppression and laryngeal relaxation exercises, but will not receive HRVB. Traditional cough suppression and laryngeal relaxation exercises include pursed lip breathing, swallowing (water, lozenge, gum, ice chips), sustained semi-occluded voicing, discussion and mitigation of triggers, maintaining a cough journal, addressing muscle tension dysphonia if indicated, and developing prophylaxis suppression and laryngeal relaxation based on stimulability. Participants in Group 1 will receive handwritten guidance indicating exercises to practice at home.
arm group label: Voice Therapy and Heart Rate Variability Biofeedback
arm group type: Active Comparator
description: Voice therapy as described in Arm 1. HRVB involves measure respiratory rate, heart rate, body temperature and skin conductance. Participants are guided through reduced breathing rate until a resonant frequency is attained. HRVB breathing simulates resonance between the baroreflex rhythm and respiration based rhythm, increasing heart rate variability and baroreceptor sensitivity. Evidence suggests HRVB improves autonomic regularity. We propose this novel modality to address centrally regulated hypersensitivity that perpetuates coughing.
arm group label: Heart Rate Variability Biofeedback
arm group type: Active Comparator
description: HRVB as indicated in Arm 2. No instruction will be provided for cough suppression, laryngeal desensitization, voice tasks or hygiene that traditionally reduces cough frequency and severity. This is the experimental arm.
intervention type: Behavioral
intervention name: Voice Therapy
description: See Arm 1 & 2
arm group label: Voice Therapy
intervention type: Behavioral
intervention name: Voice Therapy and Heart Rate Variability Biofeedback
description: See Arm 2 & 3
arm group label: Voice Therapy and Heart Rate Variability Biofeedback
intervention type: Behavioral
intervention name: Heart Rate Variability Biofeedback
description: See Arm 2 & 3
arm group label: Heart Rate Variability Biofeedback
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Philip Weissbrod, MD
phone: 858-657-8590
email: pweissbrod@ucsd.edu
last name: Erin Walsh, MA
phone: 858-657-8590
email: ehwalsh@ucsd.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Philip Weissbrod
investigator title: Director, Center for Voice and Swallowing
mesh term: Cough
submitted: July 4, 2022
returned: May 12, 2023