<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/NCT02263794</url>
  </required_header>
  <id_info>
    <org_study_id>ROB0039</org_study_id>
    <nct_id>NCT02263794</nct_id>
  </id_info>
  <brief_title>Hyperpolarized Magnetic Resonance Imaging in Asthma Pre- and Post-Bronchial Thermoplasty</brief_title>
  <official_title>Hyperpolarized Magnetic Resonance Imaging in Asthma Pre- and Post-Bronchial Thermoplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Grace Parraga</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Western University, Canada</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients in London and Hamilton with severe asthma who are deemed eligible by a respirologist&#xD;
      to undergo bronchial thermoplasty treatment will be randomized to image-guided or&#xD;
      conventional bronchial thermoplasty using hyperpolarized noble gas imaging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a one year, single centre randomized controlled trial. Subjects will be identified&#xD;
      through the London Asthma Centre located at St. Joseph's Hospital and from Hamilton at St.&#xD;
      Joseph's Healthcare, and will be given a letter of information for the study. The study will&#xD;
      only recruit subjects with asthma who are undergoing BT as part of their normal clinical care&#xD;
      and asthma treatment plan. Those interested will sign the consent form at the clinic.&#xD;
&#xD;
      Bronchial thermoplasty (BT) is a novel FDA approved outpatient asthma treatment procedure&#xD;
      which aims to &quot;cure&quot; symptoms by permanently reducing airway smooth muscle mass in the lobar&#xD;
      and segmental bronchi. Under local anesthetic, radiofrequency energy is delivered to warm the&#xD;
      airway wall to 65 degrees celcius. The effect of this procedure is a reduction in airway&#xD;
      smooth muscle mass in the treated airways resulting in a reduced potential for&#xD;
      bronchoconstriction.&#xD;
&#xD;
      Fourteen asthma patients will be enrolled in the study and each subject will visit the centre&#xD;
      on five occasions (three pre-treatment visits and two post-treatment visits). We will&#xD;
      evaluate pre-therapy optimization using inflammometry, pre-therapy ventilation defect&#xD;
      reproducibility and BT treatment effects (pre-treatment visit 1= 5±2 days pre-optimization,&#xD;
      pre-treatment visit 2 = 15±7 days pre-BT, pre-treatment visit 3 = 5±2 days pre-BT,&#xD;
      post-treatment visit 4=6 weeks post-BT, post treatment visit 5 = 6 months post-BT). At&#xD;
      pre-treatment visit 1, patients will be randomized to image-guided or conventional therapy.&#xD;
      For all subjects, at all visits, spirometry, plethysmography and 3He and/or 129Xe MRI will be&#xD;
      performed. Methacholine challenge (MCh) will be performed (for those subjects with FEV1 &gt;60%)&#xD;
      at pre-treatment visit 3 and post-treatment visit 4 with spirometry and MRI performed pre-&#xD;
      and post-MCh. Pre-treatment visit 3 will include a low-dose thoracic CT that will be used to&#xD;
      generate a detailed 3D model of the airway tree. MRI will be co-registered to the CT with 3D&#xD;
      airway rendering to enable spatial comparisons between ventilation defects and airways.&#xD;
&#xD;
      All subjects will also complete bi-weekly and weekly quality of life questionnaires.&#xD;
      Self-reported data will be uploaded by each subject monthly to our website using a&#xD;
      confidential and password protected upload.&#xD;
&#xD;
      MRI of the lungs will be performed using an inhaled contrast agent: either Hyperpolarized&#xD;
      Helium-3 or Hyperpolarized Xenon-129. Participants will inhale the hyperpolarized gas and&#xD;
      perform a breathhold for up to 16 seconds. Two different types of images will be acquired in&#xD;
      the coronal plain during each visit: 1) 1H thoracic cavity, and 2) 3He and/or 129Xe static&#xD;
      ventilation. Respiration and oxygen saturation will be monitored throughout the imaging&#xD;
      session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">September 2020</completion_date>
  <primary_completion_date type="Actual">September 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Whole lung and lobe specific ventilation defect percent (VDP) as measured by 3He or 129Xe</measure>
    <time_frame>48 +/- 2 weeks post bronchial thermoplasty treatment</time_frame>
    <description>Change in VDP post BT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function measurements</measure>
    <time_frame>48 +/- 2 weeks post bronchial thermoplasty</time_frame>
    <description>Change in pulmonary function post BT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life questionnaires</measure>
    <time_frame>48 +/- 2 weeks post bronchial thermoplasty</time_frame>
    <description>Change in subject reported QOL post BT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnea Scales</measure>
    <time_frame>48 +/- 2 weeks post bronchial thermoplasty</time_frame>
    <description>Dyspnea scale score post BT</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Image guided bronchial thermoplasty</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At pre-treatment Visit 3, imaging data will be acquired to generate a patient-specific bronchial thermoplasty treatment plan which will include 15-20 target airways, prioritized in order of importance and grouped by lobe, to be targeted during a single session BT treatment procedure. Airways demonstrating dynamic or static bronchoconstriction will be targeted for BT treatment based on their spacial proximity to ventilation defects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional bronchial thermoplasty</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in this group will undergo conventional 3 stage bronchial thermoplasty (during 3 separate bronchoscopies).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Conventional Bronchial Thermoplasty</intervention_name>
    <description>Conventional bronchial thermoplasty is performed during three bronchoscopy sessions each separated by approximately three weeks.</description>
    <arm_group_label>Conventional bronchial thermoplasty</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Image Guided Bronchial Thermoplasty</intervention_name>
    <description>Patient-specific bronchial thermoplasty based on imaging data will be performed during one bronchoscopy session.</description>
    <arm_group_label>Image guided bronchial thermoplasty</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject understands the study procedures and is willing to participate in the study as&#xD;
             indicated by signature on the informed consent&#xD;
&#xD;
          -  Male and female aged 18-60 years of age with a clinical diagnosis of asthma, as per:&#xD;
&#xD;
               -  Beta-agonist reversibility of FEV1&gt;12%, OR&#xD;
&#xD;
               -  Methacholine FEV1 PC20 ≤ 8 mg/ml if not receiving ICS or ≤ 16mg/ml if receiving&#xD;
                  an ICS.&#xD;
&#xD;
          -  Subject has asthma and is taking regular maintenance medication for the past 12 months&#xD;
             that includes:&#xD;
&#xD;
               -  Inhaled corticosteroid (ICS)&#xD;
&#xD;
               -  Long-acting beta agonist (LABA)&#xD;
&#xD;
               -  Other asthma medication such as leukotriene modifier, or anti-IgE, are acceptable&#xD;
&#xD;
          -  FEV1 &gt; 50%pred pre-bronchodilator&#xD;
&#xD;
          -  Subject assigned by the clinical team to receive bronchial thermoplasty as part of&#xD;
             their asthma treatment plan&#xD;
&#xD;
          -  Subject is a non-smoker for 1 year or greater (if former smoker less than 10 pack&#xD;
             years total smoking history).&#xD;
&#xD;
          -  Subject able to perform reproducible pulmonary function testing (i.e., the 3 best&#xD;
             acceptable spirograms have FEV1 values that do not vary more than 5% of the largest&#xD;
             value or more than 100 ml, whichever is greater.)&#xD;
&#xD;
          -  Subject is judged to be in otherwise stable health on the basis of medical history&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is, in the opinion of the investigator, mentally or legally incapacitated,&#xD;
             preventing informed consent from being obtained, or cannot read or understand the&#xD;
             written material&#xD;
&#xD;
          -  Subject is unable to perform spirometry or plethysmography maneuvers&#xD;
&#xD;
          -  Subject is pregnant&#xD;
&#xD;
          -  Recent (within 4 weeks of BL Visit 1) or current asthma exacerbation and/or&#xD;
             respiratory tract infection&#xD;
&#xD;
          -  Subject has an implanted mechanically, electrically or magnetically activated device&#xD;
             or any metal in their body which cannot be removed, including but not limited to&#xD;
             pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips,&#xD;
             bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical&#xD;
             staples (including clips or metallic sutures and/or ear implants.) (At the discretion&#xD;
             of the MRI Technologist/3T Manager)&#xD;
&#xD;
          -  In the investigator's opinion, subject suffers from any physical, psychological or&#xD;
             other condition(s) that might prevent performance of the MRI, such as severe&#xD;
             claustrophobia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grace E Parraga, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Robarts Research Institute, The University of Western Ontario</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David G McCormack, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McMaster University</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robarts Research Institute; The University of Western Ontario; London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Svenningsen S, Kirby M, Starr D, Coxson HO, Paterson NA, McCormack DG, Parraga G. What are ventilation defects in asthma? Thorax. 2014 Jan;69(1):63-71. doi: 10.1136/thoraxjnl-2013-203711. Epub 2013 Aug 16.</citation>
    <PMID>23956019</PMID>
  </reference>
  <reference>
    <citation>Janssen LJ. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo). 2012;2012:593784. doi: 10.1155/2012/593784. Epub 2012 Sep 16.</citation>
    <PMID>23024662</PMID>
  </reference>
  <reference>
    <citation>Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M; RISA Trial Study Group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91. doi: 10.1164/rccm.200704-571OC. Epub 2007 Sep 27.</citation>
    <PMID>17901415</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Western Ontario, Canada</investigator_affiliation>
    <investigator_full_name>Dr. Grace Parraga</investigator_full_name>
    <investigator_title>PhD, Scientist. Robarts Research Institute</investigator_title>
  </responsible_party>
  <keyword>Bronchial Thermoplasty</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</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/NCT02263794
org study id: ROB0039
nct id: NCT02263794
lead sponsor: 
collaborator: 
has dmc: No
Patients in London and Hamilton with severe asthma who are deemed eligible by a respirologist
      to undergo bronchial thermoplasty treatment will be randomized to image-guided or
      conventional bronchial thermoplasty using hyperpolarized noble gas imaging.
This is a one year, single centre randomized controlled trial. Subjects will be identified
      through the London Asthma Centre located at St. Joseph's Hospital and from Hamilton at St.
      Joseph's Healthcare, and will be given a letter of information for the study. The study will
      only recruit subjects with asthma who are undergoing BT as part of their normal clinical care
      and asthma treatment plan. Those interested will sign the consent form at the clinic.

      Bronchial thermoplasty (BT) is a novel FDA approved outpatient asthma treatment procedure
      which aims to "cure" symptoms by permanently reducing airway smooth muscle mass in the lobar
      and segmental bronchi. Under local anesthetic, radiofrequency energy is delivered to warm the
      airway wall to 65 degrees celcius. The effect of this procedure is a reduction in airway
      smooth muscle mass in the treated airways resulting in a reduced potential for
      bronchoconstriction.

      Fourteen asthma patients will be enrolled in the study and each subject will visit the centre
      on five occasions (three pre-treatment visits and two post-treatment visits). We will
      evaluate pre-therapy optimization using inflammometry, pre-therapy ventilation defect
      reproducibility and BT treatment effects (pre-treatment visit 1= 5±2 days pre-optimization,
      pre-treatment visit 2 = 15±7 days pre-BT, pre-treatment visit 3 = 5±2 days pre-BT,
      post-treatment visit 4=6 weeks post-BT, post treatment visit 5 = 6 months post-BT). At
      pre-treatment visit 1, patients will be randomized to image-guided or conventional therapy.
      For all subjects, at all visits, spirometry, plethysmography and 3He and/or 129Xe MRI will be
      performed. Methacholine challenge (MCh) will be performed (for those subjects with FEV1 >60%)
      at pre-treatment visit 3 and post-treatment visit 4 with spirometry and MRI performed pre-
      and post-MCh. Pre-treatment visit 3 will include a low-dose thoracic CT that will be used to
      generate a detailed 3D model of the airway tree. MRI will be co-registered to the CT with 3D
      airway rendering to enable spatial comparisons between ventilation defects and airways.

      All subjects will also complete bi-weekly and weekly quality of life questionnaires.
      Self-reported data will be uploaded by each subject monthly to our website using a
      confidential and password protected upload.

      MRI of the lungs will be performed using an inhaled contrast agent: either Hyperpolarized
      Helium-3 or Hyperpolarized Xenon-129. Participants will inhale the hyperpolarized gas and
      perform a breathhold for up to 16 seconds. Two different types of images will be acquired in
      the coronal plain during each visit: 1) 1H thoracic cavity, and 2) 3He and/or 129Xe static
      ventilation. Respiration and oxygen saturation will be monitored throughout the imaging
      session.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Whole lung and lobe specific ventilation defect percent (VDP) as measured by 3He or 129Xe
time frame: 48 +/- 2 weeks post bronchial thermoplasty treatment
description: Change in VDP post BT
measure: Pulmonary function measurements
time frame: 48 +/- 2 weeks post bronchial thermoplasty
description: Change in pulmonary function post BT
measure: Quality of Life questionnaires
time frame: 48 +/- 2 weeks post bronchial thermoplasty
description: Change in subject reported QOL post BT
measure: Dyspnea Scales
time frame: 48 +/- 2 weeks post bronchial thermoplasty
description: Dyspnea scale score post BT
arm group label: Image guided bronchial thermoplasty
arm group type: Experimental
description: At pre-treatment Visit 3, imaging data will be acquired to generate a patient-specific bronchial thermoplasty treatment plan which will include 15-20 target airways, prioritized in order of importance and grouped by lobe, to be targeted during a single session BT treatment procedure. Airways demonstrating dynamic or static bronchoconstriction will be targeted for BT treatment based on their spacial proximity to ventilation defects.
arm group label: Conventional bronchial thermoplasty
arm group type: Active Comparator
description: Patients in this group will undergo conventional 3 stage bronchial thermoplasty (during 3 separate bronchoscopies).
intervention type: Procedure
intervention name: Conventional Bronchial Thermoplasty
description: Conventional bronchial thermoplasty is performed during three bronchoscopy sessions each separated by approximately three weeks.
arm group label: Conventional bronchial thermoplasty
intervention type: Procedure
intervention name: Image Guided Bronchial Thermoplasty
description: Patient-specific bronchial thermoplasty based on imaging data will be performed during one bronchoscopy session.
arm group label: Image guided bronchial thermoplasty
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Grace E Parraga, PhD
role: Principal Investigator
affiliation: Robarts Research Institute, The University of Western Ontario
last name: David G McCormack, MD
role: Principal Investigator
affiliation: London Health Sciences Centre
facility: 
facility: 
country: Canada
citation: Svenningsen S, Kirby M, Starr D, Coxson HO, Paterson NA, McCormack DG, Parraga G. What are ventilation defects in asthma? Thorax. 2014 Jan;69(1):63-71. doi: 10.1136/thoraxjnl-2013-203711. Epub 2013 Aug 16.
PMID: 23956019
citation: Janssen LJ. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo). 2012;2012:593784. doi: 10.1155/2012/593784. Epub 2012 Sep 16.
PMID: 23024662
citation: Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M; RISA Trial Study Group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91. doi: 10.1164/rccm.200704-571OC. Epub 2007 Sep 27.
PMID: 17901415
responsible party type: Sponsor-Investigator
investigator affiliation: University of Western Ontario, Canada
investigator full name: Dr. Grace Parraga
investigator title: PhD, Scientist. Robarts Research Institute
mesh term: Asthma