<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/NCT02235025</url>
  </required_header>
  <id_info>
    <org_study_id>BAL-1</org_study_id>
    <nct_id>NCT02235025</nct_id>
  </id_info>
  <brief_title>Asymptomatic Versus Symptomatic Mild COPD: Comparisons at Rest and at Exercise</brief_title>
  <official_title>Ventilatory Constraints During Exercise in Asymptomatic Versus Symptomatic Patients With Mild COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Besancon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Besancon</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current definition of chronic obstructive pulmonary disease (COPD) is based on the&#xD;
      presence of persistent airflow obstruction assessed by spirometry. About half of the subjects&#xD;
      with mild COPD (i.e. reduced forced expiratory volume in one second (FEV1) on forced vital&#xD;
      capacity (FVC) ratio along with normal FEV1] are asymptomatic. Subjects with symptomatic mild&#xD;
      COPD have reduced exercise tolerance and abnormal dynamic ventilatory mechanics compared to&#xD;
      healthy subjects. The physiological and perceptual responses to exercise of subjects with&#xD;
      asymptomatic mild COPD are currently unknown.&#xD;
&#xD;
      The purpose of this study is to assess exercise tolerance, ventilatory constraints on tidal&#xD;
      volume expansion and dyspnoea in asymptomatic mild COPD subjects undergoing incremental cycle&#xD;
      cardiopulmonary exercise testing (CPET) to the limit of tolerance compared with symptomatic&#xD;
      mild COPD and healthy controls.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects attend one single visit. If needed, COPD subjects are asked to stop any respiratory&#xD;
      related medication such as short and long acting bronchodilators 72 hours prior to the visit.&#xD;
      Subjects are asked to arrive early in the morning. After informed consent and appropriate&#xD;
      screening of medical history, all subjects complete the mMRC scale. A complete medical&#xD;
      history is collected. Subjects thereafter complete pulmonary function testing pre- and 30-min&#xD;
      post-bronchodilator. Subjects are given a normal mixed meal and are asked not to drink&#xD;
      alcohol or coffee.&#xD;
&#xD;
      A symptom-limited incremental cycle exercise test is performed on the same day, at least 6&#xD;
      hours after the bronchodilator test and at least 4 hours after the meal. After a steady-state&#xD;
      resting period, a 3-min warm-up is conducted at about 20% of individually estimated maximal&#xD;
      work load (Wmax), and the load is increased every minute in such a way that the test duration&#xD;
      is &gt;8 and &lt;12 min. The following data are obtained breath by breath and expressed as 30-s&#xD;
      averages: V'O2 and carbon dioxide production (V'CO2); minute ventilation (V'E); tidal volume&#xD;
      (VT); respiratory rate; and ventilatory equivalents for oxygen and carbon dioxide. Blood&#xD;
      pressure is measured every minute by a sphygmomanometer. Blood samples are withdrawn from the&#xD;
      arterialized earlobe at rest and at near-maximal exercise. Tests are terminated at the point&#xD;
      of symptom limitation (peak exercise). Upon exercise cessation, subjects are asked to&#xD;
      verbalize their main reason for stopping exercise (breathing discomfort, leg discomfort or&#xD;
      both).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">August 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dyspnea intensity measured by the 10-point Borg scale during cycle exercise</measure>
    <time_frame>up to 12 minutes</time_frame>
    <description>Dyspnea intensity is measured at rest and every two minutes thereafter. Dyspnea intensity at 80% of maximal predicted work rate is calculated by linear interpolation between adjacent measurement points for each subject</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inspiratory capacity</measure>
    <time_frame>up to 12 minutes</time_frame>
    <description>Inspiratory capacity as a function of work rate is studied as a continuous variable. In addition, a decrease in inspiratory capacity from rest of more than 150 mL at any time-point during exercise defines dynamic hyperinflation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tidal volume as a function of minute ventilation</measure>
    <time_frame>up to 12 minutes</time_frame>
    <description>In the relationship between tidal volume (VT) and minute ventilation (V'E), there is an inflection point beyond which almost no further change in VT is possible despite a continued increase in V'E. This inflection in the VT response marks the point were dyspnoea sharply raises because of mechanical constraints on VT expansion. This inflection point is determined for each patient by analyzing individual Hey plot</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">111</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Asymptomatic mild COPD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects of this group have GOLD grade I COPD (post-bronchodilator FEV1 &gt; 80% predicted and FEV1/FVC &lt; 0.7). They also have a modified Medical Research Council (mMRC) score equal to zero and are free of respiratory symptoms including chronic cough and/or chronic expectoration and/or chronic wheeze.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Symptomatic mild COPD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects of this group have GOLD grade I COPD (post-bronchodilator FEV1 &gt; 80% predicted and FEV1/FVC &lt; 0.7). They also have a modified Medical Research Council (mMRC) score &gt; 0.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy controls have normal baseline spirometry (FEV1 &gt; 80% predicted, FEV1/FVC &gt; 0.7). They don't have any health problems, including cardiovascular, metabolic, neuromuscular, musculoskeletal, or respiratory diseases that could contribute to breathlessness or exercise limitation. They have a mMRC score equal to zero and do not complain any respiratory symptoms including chronic cough and/or chronic expectoration and/or chronic wheeze and/or chronic respiratory related medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cardio-pulmonary exercise testing</intervention_name>
    <arm_group_label>Asymptomatic mild COPD</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Symptomatic mild COPD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For COPD groups: post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≥ 80%&#xD;
             predicted and a FEV1/forced vital capacity (FVC) ratio &lt; 0.70&#xD;
&#xD;
          -  For the &quot;Asymptomatic mild COPD&quot; group: modified Medical Research Council (mMRC) score&#xD;
             equal to zero and absence of respiratory symptoms including chronic cough and/or&#xD;
             chronic expectoration and/or chronic wheeze.&#xD;
&#xD;
          -  For the &quot;Symptomatic mild COPD&quot; group: mMRC) score &gt; 0&#xD;
&#xD;
          -  For the &quot;Healthy controls&quot; group: FEV1 &gt; 80% predicted and FEV1/FVC &gt; 0.7) and a mMRC&#xD;
             score equal to zero and absence of respiratory symptoms including chronic cough and/or&#xD;
             chronic expectoration and/or chronic wheeze&#xD;
&#xD;
          -  Able to perform all study procedures and provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of a medical condition other than COPD that could cause or contribute to&#xD;
             breathlessness (i.e., a respiratory disease other than COPD and/or a metabolic and/or&#xD;
             a cardiovascular disease)&#xD;
&#xD;
          -  Presence of disorders other than COPD that could interfere with exercise testing, such&#xD;
             as neuromuscular diseases or musculoskeletal problems&#xD;
&#xD;
          -  History or clinical evidence of asthma&#xD;
&#xD;
          -  Use of daytime oxygen or exercise-induced arterial oxygen desaturation to &lt;80% on room&#xD;
             air&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruno Degano, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Besançon, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of respiratory diseases</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <last_update_submitted>September 5, 2014</last_update_submitted>
  <last_update_submitted_qc>September 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mild COPD</keyword>
  <keyword>dyspnea</keyword>
  <keyword>exercise</keyword>
  <keyword>respiratory mechanics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_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/NCT02235025
org study id: BAL-1
nct id: NCT02235025
lead sponsor: 
has dmc: Yes
The current definition of chronic obstructive pulmonary disease (COPD) is based on the
      presence of persistent airflow obstruction assessed by spirometry. About half of the subjects
      with mild COPD (i.e. reduced forced expiratory volume in one second (FEV1) on forced vital
      capacity (FVC) ratio along with normal FEV1] are asymptomatic. Subjects with symptomatic mild
      COPD have reduced exercise tolerance and abnormal dynamic ventilatory mechanics compared to
      healthy subjects. The physiological and perceptual responses to exercise of subjects with
      asymptomatic mild COPD are currently unknown.

      The purpose of this study is to assess exercise tolerance, ventilatory constraints on tidal
      volume expansion and dyspnoea in asymptomatic mild COPD subjects undergoing incremental cycle
      cardiopulmonary exercise testing (CPET) to the limit of tolerance compared with symptomatic
      mild COPD and healthy controls.
Subjects attend one single visit. If needed, COPD subjects are asked to stop any respiratory
      related medication such as short and long acting bronchodilators 72 hours prior to the visit.
      Subjects are asked to arrive early in the morning. After informed consent and appropriate
      screening of medical history, all subjects complete the mMRC scale. A complete medical
      history is collected. Subjects thereafter complete pulmonary function testing pre- and 30-min
      post-bronchodilator. Subjects are given a normal mixed meal and are asked not to drink
      alcohol or coffee.

      A symptom-limited incremental cycle exercise test is performed on the same day, at least 6
      hours after the bronchodilator test and at least 4 hours after the meal. After a steady-state
      resting period, a 3-min warm-up is conducted at about 20% of individually estimated maximal
      work load (Wmax), and the load is increased every minute in such a way that the test duration
      is >8 and <12 min. The following data are obtained breath by breath and expressed as 30-s
      averages: V'O2 and carbon dioxide production (V'CO2); minute ventilation (V'E); tidal volume
      (VT); respiratory rate; and ventilatory equivalents for oxygen and carbon dioxide. Blood
      pressure is measured every minute by a sphygmomanometer. Blood samples are withdrawn from the
      arterialized earlobe at rest and at near-maximal exercise. Tests are terminated at the point
      of symptom limitation (peak exercise). Upon exercise cessation, subjects are asked to
      verbalize their main reason for stopping exercise (breathing discomfort, leg discomfort or
      both).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Dyspnea intensity measured by the 10-point Borg scale during cycle exercise
time frame: up to 12 minutes
description: Dyspnea intensity is measured at rest and every two minutes thereafter. Dyspnea intensity at 80% of maximal predicted work rate is calculated by linear interpolation between adjacent measurement points for each subject
measure: Inspiratory capacity
time frame: up to 12 minutes
description: Inspiratory capacity as a function of work rate is studied as a continuous variable. In addition, a decrease in inspiratory capacity from rest of more than 150 mL at any time-point during exercise defines dynamic hyperinflation
measure: Tidal volume as a function of minute ventilation
time frame: up to 12 minutes
description: In the relationship between tidal volume (VT) and minute ventilation (V'E), there is an inflection point beyond which almost no further change in VT is possible despite a continued increase in V'E. This inflection in the VT response marks the point were dyspnoea sharply raises because of mechanical constraints on VT expansion. This inflection point is determined for each patient by analyzing individual Hey plot
arm group label: Asymptomatic mild COPD
arm group type: Other
description: Subjects of this group have GOLD grade I COPD (post-bronchodilator FEV1 > 80% predicted and FEV1/FVC < 0.7). They also have a modified Medical Research Council (mMRC) score equal to zero and are free of respiratory symptoms including chronic cough and/or chronic expectoration and/or chronic wheeze.
arm group label: Symptomatic mild COPD
arm group type: Other
description: Subjects of this group have GOLD grade I COPD (post-bronchodilator FEV1 > 80% predicted and FEV1/FVC < 0.7). They also have a modified Medical Research Council (mMRC) score > 0.
arm group label: Healthy controls
arm group type: Other
description: Healthy controls have normal baseline spirometry (FEV1 > 80% predicted, FEV1/FVC > 0.7). They don't have any health problems, including cardiovascular, metabolic, neuromuscular, musculoskeletal, or respiratory diseases that could contribute to breathlessness or exercise limitation. They have a mMRC score equal to zero and do not complain any respiratory symptoms including chronic cough and/or chronic expectoration and/or chronic wheeze and/or chronic respiratory related medication.
intervention type: Other
intervention name: Cardio-pulmonary exercise testing
arm group label: Asymptomatic mild COPD
arm group label: Healthy controls
arm group label: Symptomatic mild COPD
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Bruno Degano, MD, PhD
role: Principal Investigator
affiliation: CHU Besançon, France
facility: 
country: France
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive