<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/NCT04489758</url>
  </required_header>
  <id_info>
    <org_study_id>200473</org_study_id>
    <nct_id>NCT04489758</nct_id>
  </id_info>
  <brief_title>4DX for the Diagnosis of Constrictive Bronchiolitis</brief_title>
  <official_title>Utility of a Novel Imaging Algorithm (4DX) for the Diagnosis of Constrictive Bronchiolitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>4DMedical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</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>
      Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of&#xD;
      conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive&#xD;
      bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs)&#xD;
      are often normal. This study will determine whether analysis of fluoroscopy images using the&#xD;
      4Dx XV Ventilation Analysis software developed by 4D Medical will be able to detect&#xD;
      constrictive bronchiolitis in Veterans better than PFTs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Constrictive (or obliterative) bronchiolitis is a rare pulmonary disease characterized by&#xD;
      subepithelial inflammatory and fibrotic narrowing of the bronchioles on histologic analysis,&#xD;
      which often presents with nonspecific symptoms such as progressive dyspnea on exertion and&#xD;
      nonproductive cough over weeks to months. Constrictive bronchiolitis may be triggered by&#xD;
      autoimmune disease, chronic allograft rejection in lung transplant recipients, graft versus&#xD;
      host disease in stem cell transplant recipients, viral illness, or inhaled toxins. Although&#xD;
      pulmonary function tests (PFTs) may be helpful for the diagnosis of constrictive&#xD;
      bronchiolitis, a study performed by King and colleagues in 2009 found that many Veterans with&#xD;
      biopsy-proven constrictive bronchiolitis had normal PFTs. Thus, for these patients, more&#xD;
      sensitive methods of noninvasive testing are needed.&#xD;
&#xD;
      4Dx XV Ventilation Analysis is a new imaging analysis algorithm which utilizes standard&#xD;
      fluoroscopy to quantify ventilation with sufficient fidelity to identify regional&#xD;
      differences. Fluoroscopic images of a single tidal breath are obtained at 5 distinct angles&#xD;
      (direct AP, +/- 36 degrees, and +/- 72 degrees). Readouts from the 4Dx XV Ventilation&#xD;
      Analysis include absolute value of total lung ventilation, heterogeneity of lung ventilation,&#xD;
      a frequency distribution of lung ventilation as a line plot, and a regional map of lung&#xD;
      ventilation. In addition, an expiratory time constant (time to exhale 63% of the tidal&#xD;
      volume), heterogeneity of the expiratory time constant, frequency distribution of expiratory&#xD;
      time constant as a line plot, and a regional map of expiratory time constant are also&#xD;
      calculated. Pilot studies performed by 4D Medical show data generated by the 4Dx XV&#xD;
      Ventilation Analysis software applied to fluoroscopy is reproducible in individuals with&#xD;
      normal lung function and the heterogeneity index increases in individuals undergoing&#xD;
      radiation therapy.&#xD;
&#xD;
      The investigators hypothesize that the 4Dx XV Ventilation Analysis program, when applied to&#xD;
      standard fluoroscopic images, is more sensitive for the diagnosis of constrictive&#xD;
      bronchiolitis than PFTs in Veterans with constrictive bronchiolitis. Specific metrics that&#xD;
      will be evaluated with the software include ventilation heterogeneity and expiratory phase&#xD;
      constants, among other metrics. Endpoints will be compared during tidal breathing and a full&#xD;
      exhalation to residual volume from functional residual capacity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 25, 2021</start_date>
  <completion_date type="Actual">May 27, 2022</completion_date>
  <primary_completion_date type="Actual">May 27, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>4Dx XV Ventilation Analysis applied to fluoroscopic images</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>X-ray velocimetry results</measure>
    <time_frame>1 month</time_frame>
    <description>Heterogeneity of ventilation as detected by X-ray velocimetry</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Constrictive Bronchiolitis</condition>
  <arm_group>
    <arm_group_label>Constrictive Bronchiolitis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Veterans with surgical lung biopsy-proven constrictive bronchiolitis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Control patients with minimal smoking history and no chronic lung disease or respiratory symptoms</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis</intervention_name>
    <description>Fluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms.</description>
    <arm_group_label>Constrictive Bronchiolitis</arm_group_label>
    <arm_group_label>Controls</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Constrictive bronchiolitis arm:&#xD;
&#xD;
          -  Biopsy demonstrating constrictive bronchiolitis&#xD;
&#xD;
          -  Prior CT Chest&#xD;
&#xD;
          -  18-60 years old&#xD;
&#xD;
          -  &lt; 1 pack year history of tobacco use&#xD;
&#xD;
        Control arm:&#xD;
&#xD;
          -  18-60 years old&#xD;
&#xD;
          -  Prior CT Chest without evidence chronic lung disease as judged by a Pulmonologist&#xD;
&#xD;
          -  No clinically significant dyspnea or functional limitations&#xD;
&#xD;
          -  &lt; 1 pack year history of tobacco use&#xD;
&#xD;
        Exclusion Criteria (for both arms)&#xD;
&#xD;
          -  Pregnancy (as determined by testing on the morning prior to fluoroscopy)&#xD;
&#xD;
          -  Inability to undergo PFTs or fluoroscopy&#xD;
&#xD;
          -  Inability to raise arms above a 90-degree angle&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, Ninan M, Lambright ES, Sheller JR, Johnson JE, Miller RF. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011 Jul 21;365(3):222-30. doi: 10.1056/NEJMoa1101388. Erratum In: N Engl J Med. 2011 Nov 3;365(18):1749.</citation>
    <PMID>21774710</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>August 29, 2022</last_update_submitted>
  <last_update_submitted_qc>August 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Bradley Richmond</investigator_full_name>
    <investigator_title>Assistant Professor of Pulmonary/Critical Care Medicine</investigator_title>
  </responsible_party>
  <keyword>fluoroscopy</keyword>
  <keyword>X-ray velocimetry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiolitis</mesh_term>
    <mesh_term>Bronchiolitis Obliterans</mesh_term>
    <mesh_term>Organizing Pneumonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489758
org study id: 200473
nct id: NCT04489758
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Constrictive bronchiolitis is an uncommon lung disease that has been described in Veterans of
      conflicts in Iraq and Afghanistan. Although these Veterans have evidence of constrictive
      bronchiolitis on lung biopsies, non-invasive tests such as pulmonary function tests (PFTs)
      are often normal. This study will determine whether analysis of fluoroscopy images using the
      4Dx XV Ventilation Analysis software developed by 4D Medical will be able to detect
      constrictive bronchiolitis in Veterans better than PFTs.
Constrictive (or obliterative) bronchiolitis is a rare pulmonary disease characterized by
      subepithelial inflammatory and fibrotic narrowing of the bronchioles on histologic analysis,
      which often presents with nonspecific symptoms such as progressive dyspnea on exertion and
      nonproductive cough over weeks to months. Constrictive bronchiolitis may be triggered by
      autoimmune disease, chronic allograft rejection in lung transplant recipients, graft versus
      host disease in stem cell transplant recipients, viral illness, or inhaled toxins. Although
      pulmonary function tests (PFTs) may be helpful for the diagnosis of constrictive
      bronchiolitis, a study performed by King and colleagues in 2009 found that many Veterans with
      biopsy-proven constrictive bronchiolitis had normal PFTs. Thus, for these patients, more
      sensitive methods of noninvasive testing are needed.

      4Dx XV Ventilation Analysis is a new imaging analysis algorithm which utilizes standard
      fluoroscopy to quantify ventilation with sufficient fidelity to identify regional
      differences. Fluoroscopic images of a single tidal breath are obtained at 5 distinct angles
      (direct AP, +/- 36 degrees, and +/- 72 degrees). Readouts from the 4Dx XV Ventilation
      Analysis include absolute value of total lung ventilation, heterogeneity of lung ventilation,
      a frequency distribution of lung ventilation as a line plot, and a regional map of lung
      ventilation. In addition, an expiratory time constant (time to exhale 63% of the tidal
      volume), heterogeneity of the expiratory time constant, frequency distribution of expiratory
      time constant as a line plot, and a regional map of expiratory time constant are also
      calculated. Pilot studies performed by 4D Medical show data generated by the 4Dx XV
      Ventilation Analysis software applied to fluoroscopy is reproducible in individuals with
      normal lung function and the heterogeneity index increases in individuals undergoing
      radiation therapy.

      The investigators hypothesize that the 4Dx XV Ventilation Analysis program, when applied to
      standard fluoroscopic images, is more sensitive for the diagnosis of constrictive
      bronchiolitis than PFTs in Veterans with constrictive bronchiolitis. Specific metrics that
      will be evaluated with the software include ventilation heterogeneity and expiratory phase
      constants, among other metrics. Endpoints will be compared during tidal breathing and a full
      exhalation to residual volume from functional residual capacity.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: 4Dx XV Ventilation Analysis applied to fluoroscopic images
primary purpose: Diagnostic
masking: None (Open Label)
measure: X-ray velocimetry results
time frame: 1 month
description: Heterogeneity of ventilation as detected by X-ray velocimetry
arm group label: Constrictive Bronchiolitis
arm group type: Experimental
description: Veterans with surgical lung biopsy-proven constrictive bronchiolitis
arm group label: Controls
arm group type: Active Comparator
description: Control patients with minimal smoking history and no chronic lung disease or respiratory symptoms
intervention type: Diagnostic Test
intervention name: X-ray velocimetry analyzed by 4Dx XV Ventilation Analysis
description: Fluoroscopy will be performed for a complete tidal breath and full exhalation at 5 angles (AP, +/- 36 degrees from AP, and +/- 72 degrees from AP) while the patient's arms are raised overhead. 4Dx XV Ventilation Analysis software will be used to analyze these images. Both groups will also undergo pulmonary function testing and take a questionnaire regarding respiratory symptoms.
arm group label: Constrictive Bronchiolitis
arm group label: Controls
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: United States
citation: King MS, Eisenberg R, Newman JH, Tolle JJ, Harrell FE Jr, Nian H, Ninan M, Lambright ES, Sheller JR, Johnson JE, Miller RF. Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan. N Engl J Med. 2011 Jul 21;365(3):222-30. doi: 10.1056/NEJMoa1101388. Erratum In: N Engl J Med. 2011 Nov 3;365(18):1749.
PMID: 21774710
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Bradley Richmond
investigator title: Assistant Professor of Pulmonary/Critical Care Medicine
mesh term: Bronchiolitis
mesh term: Bronchiolitis Obliterans
mesh term: Organizing Pneumonia
sharing ipd: No