<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/NCT02241733</url>
  </required_header>
  <id_info>
    <org_study_id>O1325-R</org_study_id>
    <nct_id>NCT02241733</nct_id>
  </id_info>
  <brief_title>Sustainability of Pulmonary Rehab Gains</brief_title>
  <official_title>Sustainability of Rehabilitation Gains in COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      People with moderate to severe COPD trap air in their lungs. This lessens their ability to&#xD;
      exercise. The investigators developed a computerized breathing retraining program to help&#xD;
      patients empty their lungs during exercise. The investigators believe that learning to&#xD;
      control breathing will help patients be more active. The purpose of this study is to test the&#xD;
      effects of using breathing retraining (intervention group) versus no breathing retraining&#xD;
      (control group) as part of a 12-week exercise program. The investigators are examining the&#xD;
      long term effects of this training on exercise capacity and the ability to empty ones lungs&#xD;
      during exercise. Patients will participate in a 12-week exercise program, with or without&#xD;
      breathing retraining. They will then participate in a 42 week adherence program to maintain&#xD;
      physical activity. Patient testing will be competed at baseline, 12 weeks, 6 months and 1&#xD;
      year. 250 patients with moderate to severe COPD will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Development of dynamic hyperinflation is a primary limiting factor of exercise&#xD;
      tolerance in chronic obstructive pulmonary disease (COPD). To lessen the development of&#xD;
      dynamic hyperinflation, and to improve exercise tolerance in COPD patients, the investigators&#xD;
      have developed a breathing-retraining technique to be used during pulmonary rehabilitation.&#xD;
      This breathing-retraining technique is designed to decrease respiratory rate and prolong&#xD;
      exhalation. The investigators demonstrated that, in the short-term, hyperinflation and&#xD;
      exercise duration improved more with breathing-retraining plus exercise-training than with&#xD;
      exercise-training alone. Because a crucial aspect of pulmonary rehabilitation is the&#xD;
      maintenance its short-term benefits over the long-term, the investigators now propose to test&#xD;
      whether short-term benefits of breathing-retraining plus exercise followed by an&#xD;
      adherence-intervention program are sustainable over the long-term Primary Hypothesis: (H1) In&#xD;
      COPD patients, improvements in exercise duration on a constant- load treadmill test will be&#xD;
      greater after 12 weeks of breathing-retraining plus exercise-training followed by a 42-week&#xD;
      adherence-intervention program (1 yr. total) than after 12 weeks of exercise-training alone&#xD;
      followed by a 42-week adherence-intervention program (1 yr. total). Secondary Hypotheses: One&#xD;
      year after randomization, exercise-induced dynamic hyperinflation will be less during a&#xD;
      constant-load treadmill test (H2), 6-minute walking distance will be longer (H3), and mastery&#xD;
      over breathing will be greater (H4) in the breathing-retraining plus exercise-training group&#xD;
      than in the exercise-alone group. Lastly (exploratory objective), the investigators will&#xD;
      assess the effect of the patient's physiologic, psychologic and clinical phenotype on short-&#xD;
      term and long-term responsiveness to pulmonary rehabilitation.&#xD;
&#xD;
      Methods: The proposed study is a randomized, controlled clinical trial in which 250 patients&#xD;
      with moderate-to-severe COPD will be enrolled. One hundred forty of these patients are&#xD;
      expected to qualify for randomization into the breathing-retraining plus exercise-training&#xD;
      group or the exercise-training alone group. Patients will receive 12-weeks of supervised&#xD;
      training according to group assignment (three times weekly) followed by an&#xD;
      adherence-intervention program (weekly phone motivational interviews, home-exercise program,&#xD;
      and monthly laboratory booster sessions). Follow-up testing will be completed at 12 weeks,&#xD;
      and at 6 and 12 months. Testing will include pulmonary function test, incremental-load and&#xD;
      constant-load treadmill tests, 6-minute walk test, measurements of dyspnea, assessment of&#xD;
      respiratory and quadriceps muscle strength and endurance and quadriceps ultrasonography.&#xD;
      Analysis: In the principal analysis of the primary outcome measure (exercise duration; H1)&#xD;
      the investigators will compare changes in exercise duration (constant work-rate treadmill&#xD;
      test) from baseline to end of study using 2-sample t-test (two-tailed =.05). The primary&#xD;
      analysis will be based on intention-to-treat principles. Multiple imputation will be used for&#xD;
      study subjects missing the 12-month measurement. This imputation model will be based on&#xD;
      baseline characteristics of study participants. Several secondary analyses of the primary&#xD;
      outcome measure will be performed (H2-H4). Linear regression will be used to determine&#xD;
      whether the observed treatment benefits persist after adjustment for baseline covariates and&#xD;
      measures of adherence to treatment. Since several measurements will be taken on each patient,&#xD;
      mixed-models analysis will be used to compare the changes on the constant-load treadmill test&#xD;
      over time between the two groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2014</start_date>
  <completion_date type="Actual">August 12, 2019</completion_date>
  <primary_completion_date type="Actual">October 21, 2018</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of Exercise Time on a Constant Work-rate Treadmill Test</measure>
    <time_frame>52 week test</time_frame>
    <description>Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inspiratory Capacity</measure>
    <time_frame>52 week test</time_frame>
    <description>Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 Minute Walk Distance</measure>
    <time_frame>52 weeks</time_frame>
    <description>Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mastery Over Breathing</measure>
    <time_frame>52 weeks</time_frame>
    <description>Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery&quot; is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will exercise for 12 weeks and then participate in an adherence program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>exercise plus breathing retraining</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will exercise plus breathing retraining for 12 weeks and then participate in an adherence program</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Breathing retraining plus exercise</intervention_name>
    <description>Patients will participate in a 12-week exercise program with breathing retraining. They will also participate in an adherence program.</description>
    <arm_group_label>exercise plus breathing retraining</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise only</intervention_name>
    <description>Patients will participate in a 12-week exercise program . They will also participate in an adherence program.</description>
    <arm_group_label>exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt;/= 40 yrs&#xD;
&#xD;
          -  FEV1 &lt;/= 70% predicted&#xD;
&#xD;
          -  FEV1/FVC &lt;70% predicted&#xD;
&#xD;
          -  RV/TLC &gt;/=120%&#xD;
&#xD;
          -  SpO2 &gt;/= 90% at peak exercise (with or without exercise)&#xD;
&#xD;
          -  inspiratory capacity decline &gt;.15L from rest to peak exercise&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  respiratory infection/exacerbation within the previous 4 weeks&#xD;
&#xD;
          -  exercise limiting heart disease&#xD;
&#xD;
          -  primary asthma&#xD;
&#xD;
          -  congestive heart failure&#xD;
&#xD;
          -  exercise limiting peripheral arterial disease&#xD;
&#xD;
          -  stops exercise due to arthritic pain in the knee or hips&#xD;
&#xD;
          -  inability to walk on the treadmill&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  methadone use&#xD;
&#xD;
          -  any unforeseen illness or disability that would preclude exercise testing or training&#xD;
&#xD;
          -  participation in a formal exercise program within the previous 12 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eileen G. Collins, PhD RN</last_name>
    <role>Principal Investigator</role>
    <affiliation>Edward Hines Jr. VA Hospital, Hines, IL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Edward Hines Jr. VA Hospital, Hines, IL</name>
      <address>
        <city>Hines</city>
        <state>Illinois</state>
        <zip>60141-5000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <results_first_submitted>September 11, 2019</results_first_submitted>
  <results_first_submitted_qc>September 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 3, 2019</results_first_posted>
  <last_update_submitted>September 11, 2019</last_update_submitted>
  <last_update_submitted_qc>September 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>exercise</keyword>
  <keyword>pulmonary rehabilitation</keyword>
  <keyword>dynamic hyperinflation</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT02241733/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Exercise</title>
          <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
        </group>
        <group group_id="P2">
          <title>Exercise Plus Breathing Retraining</title>
          <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Exercise</title>
          <description>Patients will exercise for 12 weeks and then participate in an adherence program&#xD;
Exercise only: Patients will participate in a 12-week exercise program . They will also participate in an adherence program.</description>
        </group>
        <group group_id="B2">
          <title>Exercise Plus Breathing Retraining</title>
          <description>Patients will exercise plus breathing retraining for 12 weeks and then participate in an adherence program&#xD;
Breathing retraining plus exercise: Patients will participate in a 12-week exercise program with breathing retraining. They will also participate in an adherence program.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="66.5" spread="6.6"/>
                    <measurement group_id="B2" value="68.3" spread="6.6"/>
                    <measurement group_id="B3" value="67.4" spread="6.6"/>
                  </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 group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time walked on constant workload treadmill test</title>
          <units>minutes walked</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.2" spread="1.9"/>
                    <measurement group_id="B2" value="7.1" spread="2.0"/>
                    <measurement group_id="B3" value="7.2" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Inspiratory capacity</title>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.09" spread=".69"/>
                    <measurement group_id="B2" value="1.88" spread=".49"/>
                    <measurement group_id="B3" value="1.99" spread=".59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Duration of Exercise Time on a Constant Work-rate Treadmill Test</title>
        <description>Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.</description>
        <time_frame>52 week test</time_frame>
        <population>A multiple imputation model was used to impute missing values for those who did not complete the 52 weeks of the program.</population>
        <group_list>
          <group group_id="O1">
            <title>Exercise</title>
            <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
          </group>
          <group group_id="O2">
            <title>Exercise Plus Breathing Retraining</title>
            <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Exercise Time on a Constant Work-rate Treadmill Test</title>
          <description>Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.</description>
          <population>A multiple imputation model was used to impute missing values for those who did not complete the 52 weeks of the program.</population>
          <units>change in number of minutes walked</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.2" spread="3.5"/>
                    <measurement group_id="O2" value="12.5" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>An independent t-test was completed.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.94</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Inspiratory Capacity</title>
        <description>Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.</description>
        <time_frame>52 week test</time_frame>
        <population>A multiple imputation model was used to impute values for those who did not complete the program. The score below is the difference between 52 weeks and baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Exercise</title>
            <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
          </group>
          <group group_id="O2">
            <title>Exercise Plus Breathing Retraining</title>
            <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
          </group>
        </group_list>
        <measure>
          <title>Inspiratory Capacity</title>
          <description>Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.</description>
          <population>A multiple imputation model was used to impute values for those who did not complete the program. The score below is the difference between 52 weeks and baseline.</population>
          <units>difference in liters inspired</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread=".07"/>
                    <measurement group_id="O2" value=".15" spread=".07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.078</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>6 Minute Walk Distance</title>
        <description>Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.</description>
        <time_frame>52 weeks</time_frame>
        <population>Multiple imputation procedures were used to impute data for those that did not complete the protocol</population>
        <group_list>
          <group group_id="O1">
            <title>Exercise</title>
            <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
          </group>
          <group group_id="O2">
            <title>Exercise Plus Breathing Retraining</title>
            <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
          </group>
        </group_list>
        <measure>
          <title>6 Minute Walk Distance</title>
          <description>Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.</description>
          <population>Multiple imputation procedures were used to impute data for those that did not complete the protocol</population>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9" spread="8.5"/>
                    <measurement group_id="O2" value="22.8" spread="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.80</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mastery Over Breathing</title>
        <description>Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery&quot; is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.</description>
        <time_frame>52 weeks</time_frame>
        <population>Multiple imputation was used to impute missing values for those who did not complete the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Exercise</title>
            <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
          </group>
          <group group_id="O2">
            <title>Exercise Plus Breathing Retraining</title>
            <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
          </group>
        </group_list>
        <measure>
          <title>Mastery Over Breathing</title>
          <description>Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery&quot; is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.</description>
          <population>Multiple imputation was used to impute missing values for those who did not complete the protocol.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="4.9"/>
                    <measurement group_id="O2" value="2.3" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.76</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected over the course of study participation (1 year or the time the patients remained in the study).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Exercise</title>
          <description>Patients exercised for 12 weeks and then participated in an adherence program&#xD;
Exercise only: Patients participated in a 12-week exercise program . They also participated in an adherence program.</description>
        </group>
        <group group_id="E2">
          <title>Exercise Plus Breathing Retraining</title>
          <description>Patients exercised plus received breathing retraining for 12 weeks and then participated in an adherence program&#xD;
Breathing retraining plus exercise: Patients participated in a 12-week exercise program with breathing retraining. They also participated in an adherence program.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>cellulitis</sub_title>
                <description>Patient developed severe cellulitis of the leg and was hospitalized</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>leukemia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>patient developed leukemia and died</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <description>Atrial fibrillation with rapid ventricular response. Required hospitalization.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Rectal abscess</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>Hospitalized for severe rectal abscess</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>brain aneurysm</sub_title>
                <description>patient hospitalized and died from brain aneurysm</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>meningioma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney stones</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>hospitalized for kidney stones</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD Exacerbation</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>Exacerbation requiring hospitalization or ED visit</description>
                <counts group_id="E1" events="15" subjects_affected="13" subjects_at_risk="40"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Eileen Collins RN, PhD, Research Nurse Scientist</name_or_title>
      <organization>Edward Hines Jr., VA Hospital</organization>
      <phone>312-413-5621</phone>
      <email>ecollins@uic.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/NCT02241733
org study id: O1325-R
nct id: NCT02241733
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
People with moderate to severe COPD trap air in their lungs. This lessens their ability to
      exercise. The investigators developed a computerized breathing retraining program to help
      patients empty their lungs during exercise. The investigators believe that learning to
      control breathing will help patients be more active. The purpose of this study is to test the
      effects of using breathing retraining (intervention group) versus no breathing retraining
      (control group) as part of a 12-week exercise program. The investigators are examining the
      long term effects of this training on exercise capacity and the ability to empty ones lungs
      during exercise. Patients will participate in a 12-week exercise program, with or without
      breathing retraining. They will then participate in a 42 week adherence program to maintain
      physical activity. Patient testing will be competed at baseline, 12 weeks, 6 months and 1
      year. 250 patients with moderate to severe COPD will be enrolled.
Rationale: Development of dynamic hyperinflation is a primary limiting factor of exercise
      tolerance in chronic obstructive pulmonary disease (COPD). To lessen the development of
      dynamic hyperinflation, and to improve exercise tolerance in COPD patients, the investigators
      have developed a breathing-retraining technique to be used during pulmonary rehabilitation.
      This breathing-retraining technique is designed to decrease respiratory rate and prolong
      exhalation. The investigators demonstrated that, in the short-term, hyperinflation and
      exercise duration improved more with breathing-retraining plus exercise-training than with
      exercise-training alone. Because a crucial aspect of pulmonary rehabilitation is the
      maintenance its short-term benefits over the long-term, the investigators now propose to test
      whether short-term benefits of breathing-retraining plus exercise followed by an
      adherence-intervention program are sustainable over the long-term Primary Hypothesis: (H1) In
      COPD patients, improvements in exercise duration on a constant- load treadmill test will be
      greater after 12 weeks of breathing-retraining plus exercise-training followed by a 42-week
      adherence-intervention program (1 yr. total) than after 12 weeks of exercise-training alone
      followed by a 42-week adherence-intervention program (1 yr. total). Secondary Hypotheses: One
      year after randomization, exercise-induced dynamic hyperinflation will be less during a
      constant-load treadmill test (H2), 6-minute walking distance will be longer (H3), and mastery
      over breathing will be greater (H4) in the breathing-retraining plus exercise-training group
      than in the exercise-alone group. Lastly (exploratory objective), the investigators will
      assess the effect of the patient's physiologic, psychologic and clinical phenotype on short-
      term and long-term responsiveness to pulmonary rehabilitation.

      Methods: The proposed study is a randomized, controlled clinical trial in which 250 patients
      with moderate-to-severe COPD will be enrolled. One hundred forty of these patients are
      expected to qualify for randomization into the breathing-retraining plus exercise-training
      group or the exercise-training alone group. Patients will receive 12-weeks of supervised
      training according to group assignment (three times weekly) followed by an
      adherence-intervention program (weekly phone motivational interviews, home-exercise program,
      and monthly laboratory booster sessions). Follow-up testing will be completed at 12 weeks,
      and at 6 and 12 months. Testing will include pulmonary function test, incremental-load and
      constant-load treadmill tests, 6-minute walk test, measurements of dyspnea, assessment of
      respiratory and quadriceps muscle strength and endurance and quadriceps ultrasonography.
      Analysis: In the principal analysis of the primary outcome measure (exercise duration; H1)
      the investigators will compare changes in exercise duration (constant work-rate treadmill
      test) from baseline to end of study using 2-sample t-test (two-tailed =.05). The primary
      analysis will be based on intention-to-treat principles. Multiple imputation will be used for
      study subjects missing the 12-month measurement. This imputation model will be based on
      baseline characteristics of study participants. Several secondary analyses of the primary
      outcome measure will be performed (H2-H4). Linear regression will be used to determine
      whether the observed treatment benefits persist after adjustment for baseline covariates and
      measures of adherence to treatment. Since several measurements will be taken on each patient,
      mixed-models analysis will be used to compare the changes on the constant-load treadmill test
      over time between the two groups.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Duration of Exercise Time on a Constant Work-rate Treadmill Test
time frame: 52 week test
description: Patients walk on a treadmill set at a constant workrate. The difference in the time walked on the treadmill from baseline to study completion is the primary outcome measure.
measure: Inspiratory Capacity
time frame: 52 week test
description: Inspiratory capacity is measured at a set time during the constant workrate treadmill test. The difference between the inspiratory capacity measured at baseline and 52 weeks is a secondary outcome. Inspiratory capacity measured during exercise is a measure of dynamic hyperinflation.
measure: 6 Minute Walk Distance
time frame: 52 weeks
description: Six-minute walk distance will be measured at 52 weeks. The difference in distance walked in meters between baseline and 52 weeks is the secondary outcome measure. The 6 minute walk is conducted using the guidelines issued by the American Thoracic Society.
measure: Mastery Over Breathing
time frame: 52 weeks
description: Mastery over breathing is measured using the Chronic Respiratory Disease Questionnaire. Specifically the subscale 'mastery" is the investigators' secondary outcome. The difference in scores from baseline to 52 weeks is the investigators' outcome measure. The Chronic Respiratory Disease Questionnaire is a valid and reliable questionnaire. 1=minimum score, 7=maximum with the higher score indicating greater mastery. A higher score indicates better health. A change of 0.5 indicates a small change, 1.0 indicates a moderate change and greater or equal to a change of 1.5 indicates a large change.
arm group label: exercise
arm group type: Active Comparator
description: Patients will exercise for 12 weeks and then participate in an adherence program
arm group label: exercise plus breathing retraining
arm group type: Experimental
description: Patients will exercise plus breathing retraining for 12 weeks and then participate in an adherence program
intervention type: Behavioral
intervention name: Breathing retraining plus exercise
description: Patients will participate in a 12-week exercise program with breathing retraining. They will also participate in an adherence program.
arm group label: exercise plus breathing retraining
intervention type: Behavioral
intervention name: Exercise only
description: Patients will participate in a 12-week exercise program . They will also participate in an adherence program.
arm group label: exercise
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Eileen G. Collins, PhD RN
role: Principal Investigator
affiliation: Edward Hines Jr. VA Hospital, Hines, IL
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 