<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/NCT03290898</url>
  </required_header>
  <id_info>
    <org_study_id>REPLACE</org_study_id>
    <nct_id>NCT03290898</nct_id>
  </id_info>
  <brief_title>REPLACE: Can Exercise Replace Inhaled Corticosteroid Treatment in Asthma? A RCT</brief_title>
  <official_title>REPLACE: Can Exercise Replace Inhaled Corticosteroid Treatment in Asthma? A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bispebjerg Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bispebjerg Hospital</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate if physical exercise intervention leads to an improved asthma control as measured&#xD;
      by Asthma Control Questionnaire (ACQ-5) in such a magnitude that inhaled corticosteroid can&#xD;
      be reduces in asthmatics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At least 102 asthmatics will be randomized 2:1 (2 to training group; 1 to control) and&#xD;
      undergo 6 months of intervention or usual lifestyle.&#xD;
&#xD;
      Subjects must have confirmed asthma diagnosis, on a stable treatment with inhaled&#xD;
      corticosteroid, symptomatic and untrained.&#xD;
&#xD;
      At enrollment and during the study asthma medicine is adjusted based on asthma symptoms&#xD;
      evaluated by ACQ-5. 6 treatment steps are pre-defined, and if well controlled asthma,&#xD;
      subjects are down-titrated one step, if uncontrolled, subjects are uptitrated one step.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Actual">December 4, 2020</completion_date>
  <primary_completion_date type="Actual">June 26, 2020</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>A randomized, controlled parallel group, outcome assessor blinded, clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>Single blindet, randomization and training intervention by non-investigator. Open-label after primary follow up. After unblinding, blindet 3rd party performs tests (visit 9 and 12 months, e.g. spirometry)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Reduced inhaled corticosteroid (ICS) 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>The proportion of participants at 6 months that have been down-titrated in ICS dose by at least 25% compared to the participants' baseline dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduced inhaled corticosteroid (ICS) 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>The proportion of participants at 12 months that have been down-titrated in ICS dose by at least 25 % compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulated ICS 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in cumulated dose of ICS at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulated ICS 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in cumulated dose of ICS at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulated Long acting beta2 agonists (LABA) 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in cumulated dose of LABA at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulated LABA 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in cumulated dose of LABA at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exacerbation rate 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Number of exacerbations (moderate-severe) at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exacerbation rate 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Number of exacerbations (moderate-severe) at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>miniAQLQ 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in Asthma life quality evaluated by miniAQLQ at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>miniAQLQ 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in Asthma life quality evaluated by miniAQLQ at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of exhaled Nitrogen Oxid 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in Airway inflammation evaluated by FeNO at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of exhaled Nitrogen Oxid 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in Airway inflammation evaluated by FeNO at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum cell count 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in Airway inflammation evaluated by sputum cell count at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum cell count 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in Airway inflammation evaluated by sputum cell count at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammation 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammation 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway hyperresponsiveness</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in airway hyperresponsiveness measured by methacholine test at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in lung function evaluated by FEV1 at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in lung function evaluated by FVC at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in lung function evaluated by FEV1 at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>Change from baseline in lung function evaluated by FVC at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiopulmonary fitness</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in cardiopulmonary fitness evaluated by maximum oxygen consumption at 6 months (VO2max)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fat and muscle composition (DEXA scan)</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>Change from baseline in fat and muscle composition evaluated by DEXA scan</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Eosinophilic subpopulation - exploratory analyses 6 months</measure>
    <time_frame>6 months +/- 7 days</time_frame>
    <description>To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics. Both regarding primary outcome and secondary outcomes.</description>
  </other_outcome>
  <other_outcome>
    <measure>Eosinophilic subpopulation - exploratory analyses 12 months</measure>
    <time_frame>12 months +/- 7 days</time_frame>
    <description>To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics with regards to secondary outcomes at 12 months.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Training group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Supervised High intensity interval training (HIIT) 3 times a week for 6 months.&#xD;
Training session:&#xD;
10 minutes warm up (Low-moderate intensity) 30 minutes intervention (16 minutes HIIT) 10 minutes cool down(Low-moderate intensity)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control group, usual lifestyle. Aside from training intervention, all other visits are the same as intervention group (training).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>High Intensity Interval Training</intervention_name>
    <description>Training (HIIT)</description>
    <arm_group_label>Training group</arm_group_label>
    <other_name>Training group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Asthma (The diagnose of asthma is based on symptoms and at least one positive asthma&#xD;
             test the last 5 years (AHR to either mannitol or methacholine, reversibility to&#xD;
             beta2-agonist, peak flow variation or positive eucapnic voluntary hyperventilation&#xD;
             test))&#xD;
&#xD;
          -  ACQ ≥ 1 and ≤ 2.5&#xD;
&#xD;
          -  On a daily dose of ICS at a minimum of 400 µg budesonide or equivalent ICS for 3&#xD;
             months and with no changes in asthma medicine 4 weeks prior to enrollment&#xD;
&#xD;
          -  Untrained (no participation in vigorous exercise for more than 1 hour per week during&#xD;
             the last 2 month)&#xD;
&#xD;
          -  Capable of exercising on bike&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to speak and understand Danish&#xD;
&#xD;
          -  Infection within 4 weeks prior to visit 100*&#xD;
&#xD;
          -  Asthma exacerbation within 4 weeks prior to visit 100*&#xD;
&#xD;
          -  Hospitalized for an asthma attack during the last 2 months&#xD;
&#xD;
          -  Treatment with immunotherapy within 5 T½ of the treatment drug prior to visit 100&#xD;
&#xD;
          -  Initiation of allergen immunotherapy within 3 months prior to visit 100 or plan to&#xD;
             begin therapy during study period&#xD;
&#xD;
          -  Treatment with peroral prednisolone&#xD;
&#xD;
          -  Respiratory: other chronic pulmonary disease of clinically significance&#xD;
&#xD;
          -  Cardiovascular: Unstable ischemic heart disease, myocardial infarction within the last&#xD;
             12 months, symptomatic heart failure (NYHA III-IV or EF &lt;40%), symptomatic heart&#xD;
             arrhythmia (documented with ECG), uncontrolled hypertension (&gt;155/100)&#xD;
&#xD;
          -  Pregnancy or breastfeeding or planned pregnancy within the next 12 months&#xD;
&#xD;
          -  Other inflammatory or metabolic diseases with the exception of rhinitis, atopy and&#xD;
             well-controlled hypothyroidism treated with or without Eltroxin&#xD;
&#xD;
          -  Vaccination less than 2 weeks prior to any visit&#xD;
&#xD;
          -  Current or former smokers with &gt; 20 pack years&#xD;
&#xD;
          -  Subjects, who by investigators determination, will not be able to adhere to study&#xD;
             protocol&#xD;
&#xD;
               -  If patients are excluded due to a recent infection or exacerbation they can&#xD;
                  undergo re-screening after a total of 4 weeks after end of exacerbation&#xD;
                  treatment/clearing the infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vibeke Backer, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Respiratory Research Unit, Birpebjerg Hospital</name>
      <address>
        <city>Copenhagen NV</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>March 11, 2021</last_update_submitted>
  <last_update_submitted_qc>March 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bispebjerg Hospital</investigator_affiliation>
    <investigator_full_name>Vibeke Backer</investigator_full_name>
    <investigator_title>Professor dr.med.</investigator_title>
  </responsible_party>
  <keyword>Asthma</keyword>
  <keyword>Exercise</keyword>
  <keyword>Asthma treatment</keyword>
  <keyword>Inhaled corticosteroid</keyword>
  <keyword>Rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03290898/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03290898/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03290898
org study id: REPLACE
nct id: NCT03290898
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To evaluate if physical exercise intervention leads to an improved asthma control as measured
      by Asthma Control Questionnaire (ACQ-5) in such a magnitude that inhaled corticosteroid can
      be reduces in asthmatics.
At least 102 asthmatics will be randomized 2:1 (2 to training group; 1 to control) and
      undergo 6 months of intervention or usual lifestyle.

      Subjects must have confirmed asthma diagnosis, on a stable treatment with inhaled
      corticosteroid, symptomatic and untrained.

      At enrollment and during the study asthma medicine is adjusted based on asthma symptoms
      evaluated by ACQ-5. 6 treatment steps are pre-defined, and if well controlled asthma,
      subjects are down-titrated one step, if uncontrolled, subjects are uptitrated one step.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A randomized, controlled parallel group, outcome assessor blinded, clinical trial
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: Single blindet, randomization and training intervention by non-investigator. Open-label after primary follow up. After unblinding, blindet 3rd party performs tests (visit 9 and 12 months, e.g. spirometry)
measure: Reduced inhaled corticosteroid (ICS) 6 months
time frame: 6 months +/- 7 days
description: The proportion of participants at 6 months that have been down-titrated in ICS dose by at least 25% compared to the participants' baseline dose
measure: Reduced inhaled corticosteroid (ICS) 12 months
time frame: 12 months +/- 7 days
description: The proportion of participants at 12 months that have been down-titrated in ICS dose by at least 25 % compared to baseline.
measure: Cumulated ICS 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in cumulated dose of ICS at 6 months
measure: Cumulated ICS 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in cumulated dose of ICS at 12 months
measure: Cumulated Long acting beta2 agonists (LABA) 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in cumulated dose of LABA at 6 months
measure: Cumulated LABA 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in cumulated dose of LABA at 12 months
measure: Exacerbation rate 6 months
time frame: 6 months +/- 7 days
description: Number of exacerbations (moderate-severe) at 6 months
measure: Exacerbation rate 12 months
time frame: 12 months +/- 7 days
description: Number of exacerbations (moderate-severe) at 12 months
measure: miniAQLQ 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in Asthma life quality evaluated by miniAQLQ at 6 months
measure: miniAQLQ 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in Asthma life quality evaluated by miniAQLQ at 12 months
measure: Fraction of exhaled Nitrogen Oxid 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in Airway inflammation evaluated by FeNO at 6 months
measure: Fraction of exhaled Nitrogen Oxid 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in Airway inflammation evaluated by FeNO at 12 months
measure: Sputum cell count 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in Airway inflammation evaluated by sputum cell count at 6 months
measure: Sputum cell count 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in Airway inflammation evaluated by sputum cell count at 12 months
measure: Systemic inflammation 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 6 months
measure: Systemic inflammation 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 12 months
measure: Airway hyperresponsiveness
time frame: 6 months +/- 7 days
description: Change from baseline in airway hyperresponsiveness measured by methacholine test at 6 months
measure: FEV1 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in lung function evaluated by FEV1 at 6 months
measure: FVC 6 months
time frame: 6 months +/- 7 days
description: Change from baseline in lung function evaluated by FVC at 6 months
measure: FEV1 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in lung function evaluated by FEV1 at 12 months
measure: FVC 12 months
time frame: 12 months +/- 7 days
description: Change from baseline in lung function evaluated by FVC at 12 months
measure: Cardiopulmonary fitness
time frame: 6 months +/- 7 days
description: Change from baseline in cardiopulmonary fitness evaluated by maximum oxygen consumption at 6 months (VO2max)
measure: Change in fat and muscle composition (DEXA scan)
time frame: 6 months +/- 7 days
description: Change from baseline in fat and muscle composition evaluated by DEXA scan
measure: Eosinophilic subpopulation - exploratory analyses 6 months
time frame: 6 months +/- 7 days
description: To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics. Both regarding primary outcome and secondary outcomes.
measure: Eosinophilic subpopulation - exploratory analyses 12 months
time frame: 12 months +/- 7 days
description: To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics with regards to secondary outcomes at 12 months.
arm group label: Training group
arm group type: Active Comparator
description: Supervised High intensity interval training (HIIT) 3 times a week for 6 months.
Training session:
10 minutes warm up (Low-moderate intensity) 30 minutes intervention (16 minutes HIIT) 10 minutes cool down(Low-moderate intensity)
arm group label: Control group
arm group type: No Intervention
description: Control group, usual lifestyle. Aside from training intervention, all other visits are the same as intervention group (training).
intervention type: Behavioral
intervention name: High Intensity Interval Training
description: Training (HIIT)
arm group label: Training group
other name: Training group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Vibeke Backer, professor
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Bispebjerg Hospital
investigator full name: Vibeke Backer
investigator title: Professor dr.med.
mesh term: Asthma
sharing ipd: No
provided document: 
provided document: 