<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/NCT02989935</url>
  </required_header>
  <id_info>
    <org_study_id>REB16-0147</org_study_id>
    <nct_id>NCT02989935</nct_id>
  </id_info>
  <brief_title>RELVAR Effects on Parasternal Muscle Activity, Diaphragm, and Ventilation in Severe COPD</brief_title>
  <official_title>RELVAR Effects on Parasternal Muscle Activity, Diaphragm, and Ventilation in Severe COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Calgary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study examines the effect of the ultra long acting beta agonist/corticosteroid&#xD;
      bronchodilator combination fluticasone furoate/vilanterol trifenatate, on respiratory muscles&#xD;
      and ventilation in adults with severe bronchitis or emphysema (COPD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In adults with severe, minimally reversible bronchitis or emphysema (COPD), there is&#xD;
      progressive hyperinflation of the lungs with associated flattening and inefficiency of the&#xD;
      major respiratory muscle, the diaphragm. These changes limit physical activity and exercise,&#xD;
      and provoke shortness of breath - dyspnea.&#xD;
&#xD;
      These debilitating symptoms are often significantly lessened with ultra long acting&#xD;
      combination bronchodilators, even in adults where the bronchodilator does not produce any&#xD;
      measurable improvement in either airflow or lung hyperinflation.&#xD;
&#xD;
      This symptomatic improvement in adults with severe, minimally reversible COPD may occur&#xD;
      because of a direct benefit of the bronchodilator on respiratory muscles and ventilation.&#xD;
&#xD;
      This study examines the effect of the ultra long acting bronchodilator fluticasone&#xD;
      furoate/vilanterol trifenatate upon the upper anterior chest wall respiratory muscles&#xD;
      (parasternals), the diaphragm, and breathing pattern.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>April 2016</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Study of RELVAR drug effect on respiratory physiology variables including breathing pattern, and EMG.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Minute ventilation change</measure>
    <time_frame>2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.</time_frame>
    <description>Minute ventilation will be averaged and compared, before and then 2 hours after the bronchodilator inhalation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Parasternal EMG change</measure>
    <time_frame>2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.</time_frame>
    <description>Change in moving averaged, EMG continuously recorded from the parasternal intercostal muscle.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pressure change with phrenic stimulation</measure>
    <time_frame>2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.</time_frame>
    <description>Change in recorded mouth pressure during magnetic stimulation of the phrenic nerves.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Copd</condition>
  <arm_group>
    <arm_group_label>Fluticasone vilanterol bronchodilator</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inhalation of fluticasone furoate/vilanterol trifenatate, 100 mcg/25 mcg combination, bronchodilator,using standard dry powder inhaler.&#xD;
Interventions include ventilation, parasternal EMG, and phrenic magnetic stimulation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ventilation</intervention_name>
    <description>Measurements of ventilation with subjects seated, and breathing across a pneumotachygraph and pressure transducer to measure inspiratory airflow, during both resting and CO2 stimulated breathing.</description>
    <arm_group_label>Fluticasone vilanterol bronchodilator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Parasternal EMG</intervention_name>
    <description>Recordings of electrical activity (EMG) from the parasternal intercostal muscle in the second intercostal space on the upper anterior chest wall adjacent to the sternum.</description>
    <arm_group_label>Fluticasone vilanterol bronchodilator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Phrenic magnetic stimulation</intervention_name>
    <description>Bilateral maximal magnetic stimulation (Magstim) of the phrenic nerves.</description>
    <arm_group_label>Fluticasone vilanterol bronchodilator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ambulatory, stable severe COPD (GOLD Class III-IV)&#xD;
&#xD;
          -  on long acting bronchodilator therapy&#xD;
&#xD;
          -  compliant with use of prescribed medications&#xD;
&#xD;
          -  fit for minor surgical procedure including intravenous sedation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  hypersensitivity to milk proteins&#xD;
&#xD;
          -  hypersensitive to fluticasone furoate/vilanterol formulation&#xD;
&#xD;
          -  angina or substantial cardiovascular risk&#xD;
&#xD;
          -  exacerbation of COPD within the preceding 2 months&#xD;
&#xD;
          -  significant non-respiratory system disease&#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>Paul A Easton, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N4N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Easton PA, Hawes HG, Doig CJ, Johnson MW, Yokoba M, Wilde ER. Parasternal muscle activity decreases in severe COPD with salmeterol-fluticasone propionate. Chest. 2010 Mar;137(3):558-65. doi: 10.1378/chest.09-0197. Epub 2009 Oct 9.</citation>
    <PMID>19820074</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>August 6, 2023</last_update_submitted>
  <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Paul Easton</investigator_full_name>
    <investigator_title>Assoc.Prof. University of Calgary</investigator_title>
  </responsible_party>
  <keyword>respiratory muscle</keyword>
  <keyword>bronchodilator</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Participant physiologic results and measurements publicly presented.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>During 2020 as final results are available.</ipd_time_frame>
    <ipd_access_criteria>By researcher contact or inquiry</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT02989935
org study id: REB16-0147
nct id: NCT02989935
lead sponsor: 
has dmc: No
This study examines the effect of the ultra long acting beta agonist/corticosteroid
      bronchodilator combination fluticasone furoate/vilanterol trifenatate, on respiratory muscles
      and ventilation in adults with severe bronchitis or emphysema (COPD).
In adults with severe, minimally reversible bronchitis or emphysema (COPD), there is
      progressive hyperinflation of the lungs with associated flattening and inefficiency of the
      major respiratory muscle, the diaphragm. These changes limit physical activity and exercise,
      and provoke shortness of breath - dyspnea.

      These debilitating symptoms are often significantly lessened with ultra long acting
      combination bronchodilators, even in adults where the bronchodilator does not produce any
      measurable improvement in either airflow or lung hyperinflation.

      This symptomatic improvement in adults with severe, minimally reversible COPD may occur
      because of a direct benefit of the bronchodilator on respiratory muscles and ventilation.

      This study examines the effect of the ultra long acting bronchodilator fluticasone
      furoate/vilanterol trifenatate upon the upper anterior chest wall respiratory muscles
      (parasternals), the diaphragm, and breathing pattern.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Study of RELVAR drug effect on respiratory physiology variables including breathing pattern, and EMG.
primary purpose: Basic Science
masking: None (Open Label)
measure: Minute ventilation change
time frame: 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.
description: Minute ventilation will be averaged and compared, before and then 2 hours after the bronchodilator inhalation.
measure: Parasternal EMG change
time frame: 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.
description: Change in moving averaged, EMG continuously recorded from the parasternal intercostal muscle.
measure: Pressure change with phrenic stimulation
time frame: 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation.
description: Change in recorded mouth pressure during magnetic stimulation of the phrenic nerves.
arm group label: Fluticasone vilanterol bronchodilator
arm group type: Experimental
description: Inhalation of fluticasone furoate/vilanterol trifenatate, 100 mcg/25 mcg combination, bronchodilator,using standard dry powder inhaler.
Interventions include ventilation, parasternal EMG, and phrenic magnetic stimulation.
intervention type: Procedure
intervention name: Ventilation
description: Measurements of ventilation with subjects seated, and breathing across a pneumotachygraph and pressure transducer to measure inspiratory airflow, during both resting and CO2 stimulated breathing.
arm group label: Fluticasone vilanterol bronchodilator
intervention type: Procedure
intervention name: Parasternal EMG
description: Recordings of electrical activity (EMG) from the parasternal intercostal muscle in the second intercostal space on the upper anterior chest wall adjacent to the sternum.
arm group label: Fluticasone vilanterol bronchodilator
intervention type: Procedure
intervention name: Phrenic magnetic stimulation
description: Bilateral maximal magnetic stimulation (Magstim) of the phrenic nerves.
arm group label: Fluticasone vilanterol bronchodilator
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul A Easton, MD, PhD
role: Principal Investigator
affiliation: University of Calgary
facility: 
country: Canada
citation: Easton PA, Hawes HG, Doig CJ, Johnson MW, Yokoba M, Wilde ER. Parasternal muscle activity decreases in severe COPD with salmeterol-fluticasone propionate. Chest. 2010 Mar;137(3):558-65. doi: 10.1378/chest.09-0197. Epub 2009 Oct 9.
PMID: 19820074
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Paul Easton
investigator title: Assoc.Prof. University of Calgary
sharing ipd: Yes
ipd description: Participant physiologic results and measurements publicly presented.
ipd info type: Study Protocol
ipd time frame: During 2020 as final results are available.
ipd access criteria: By researcher contact or inquiry