<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/NCT03237364</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00076112</org_study_id>
    <nct_id>NCT03237364</nct_id>
  </id_info>
  <brief_title>Iraq- Afghanistan War Lung Injury Using 19F MRI (DIAL1001006)</brief_title>
  <official_title>Evaluation of Regional Lung Function in U.S. Soldiers With Suspected Iraq-Afghanistan War Lung Injury Using 19F MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hal C Charles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to evaluate the utilization of conventional 'thermally' polarized&#xD;
      perfluorinated gases mixed with oxygen as an exogenous inert contrast agent to image the&#xD;
      airway spaces in subjects with suspected lung disease, post deployment in Iraq and&#xD;
      Afghanistan. This is an open label proof of concept study expanding on work here at Duke.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There has been mounting evidence of respiratory problems related to military service in the&#xD;
      Middle East especially in the past two decades. An overview by Flavo et al. summarizes&#xD;
      studies not only of soldiers but evaluation of particulates from the Middle East in a number&#xD;
      of animal models. While there have been some 'prospective' studies based on use of a standard&#xD;
      evaluation protocol post deployment, the primary imaging modalities have been chest&#xD;
      radiograph (most read as normal) and chest high resolution computed tomography (HRCT),&#xD;
      neither of which have significant functional information. Standard pulmonary function testing&#xD;
      (e.g. spirometry, lung volumes, diffusing capacity, bronchoalveolar lavage, as well as&#xD;
      oscillatory resistance) were used in the STAMPEDE study, but only provide global functional&#xD;
      information. The case study by King et al. included lung biopsy in a sub-cohort (n = 49) of&#xD;
      soldiers with varying degrees of inhalation exposure during deployment. All biopsy samples&#xD;
      were abnormal and some were consistent with constrictive bronchiolitis. Constrictive&#xD;
      bronchiolitis is a non-reversible bronchiolar airway disease that is characterized by&#xD;
      fibrosis of the bronchioles and can be challenging to diagnose without biopsy (it is also&#xD;
      known by the term 'bronchiolitis obliterans'). The chest radiographs were normal in these&#xD;
      subjects although about 25% of chest CT showed 'air trapping' or 'centrilobular nodules'.&#xD;
      Pulmonary function testing in 39 soldiers with HRCT showed normal to near normal results in&#xD;
      32 of the subjects, with seven showing low diffusion capacity, obstruction and/or&#xD;
      restriction. Clearly, neither global measures of lung function nor high resolution anatomic&#xD;
      imaging are sensitive enough to avoid a biopsy to confirm diagnosis of constrictive&#xD;
      bronchiolitis. We hypothesize that measures of regional lung function should provide&#xD;
      additional information to aid in the diagnosis of WLI and may assist in the management of&#xD;
      more difficult or advanced cases of WLI.&#xD;
&#xD;
      This is an open label study in up to 10 subjects being evaluated for post war lung injury.&#xD;
      Each subject will receive up to 25 liters of inert perfluoropropane/oxygen gas mixtures as a&#xD;
      contrast agent to visualize the airway and alveolar spaces in their lungs using 19F magnetic&#xD;
      resonance imaging of inert gas/oxygen mixtures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 19, 2017</start_date>
  <completion_date type="Actual">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lung Ventilatory Heterogeneity defined by parametric imaging with 19F perfluorinated gas/oxygen mixtures</measure>
    <time_frame>one hour</time_frame>
    <description>Fraction of lung with slow filling compartments compared to historic norms.</description>
  </primary_outcome>
  <enrollment type="Actual">7</enrollment>
  <condition>Constrictive Bronchiolitis</condition>
  <condition>Iraq-Afganistan War Lung Injury Syndrome</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Perfluorinated Gas/Oxygen Mixture</intervention_name>
    <description>19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, &lt; 1 hour</description>
    <other_name>Perfluorinated Propane Imaging</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must meet all of the following inclusion criteria to be eligible for&#xD;
             enrollment into the trial&#xD;
&#xD;
               1. Outpatients of either gender, age &gt; 18.&#xD;
&#xD;
               2. Willing and able to give informed consent and adhere to visit/protocol schedules.&#xD;
                  (Consent must be given before any study procedures are performed.)&#xD;
&#xD;
               3. Women of childbearing potential must have a negative serum pregnancy test. This&#xD;
                  will be confirmed before participation in this investigational protocol.&#xD;
&#xD;
               4. Subjects must have been deployed in Iraq and/or Afghanistan&#xD;
&#xD;
               5. Subjects must have a strong clinical suspicion of a diagnosis of constrictive&#xD;
                  bronchiolitis based on clinical presentation and spirometry results&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects presenting with any of the following will not be included in the trial:&#xD;
&#xD;
               1. Unable to undergo a 3.0-Tesla MRI exam of the lungs and chest because of&#xD;
                  contraindications (e.g. metal in the eye, claustrophobia);&#xD;
&#xD;
               2. Medical or psychological conditions which, in the opinion of the investigator,&#xD;
                  might create undue risk to the subject or interfere with the subject's ability to&#xD;
                  comply with the protocol requirements&#xD;
&#xD;
               3. Unable to receive gas mixture by breathing because of contraindications;&#xD;
&#xD;
               4. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
                  abnormality that may increase the risk associated with trial participation or may&#xD;
                  interfere with the interpretation of trial results and, in the judgment of the&#xD;
                  investigator, would make the subject inappropriate for entry into this trial.&#xD;
&#xD;
        Female; women at risk of pregnancy are required to have a confirmed negative urine&#xD;
        pregnancy test at Screening if of childbearing potential prior to the MRI scan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cecil Charles, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University Medical Center, Department of Radiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke Image Analysis Laboratory</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>March 9, 2020</last_update_submitted>
  <last_update_submitted_qc>March 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Hal C Charles</investigator_full_name>
    <investigator_title>Assistant Professor of Radiology</investigator_title>
  </responsible_party>
  <keyword>deployed in Iraq and/or Afghanistan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiolitis</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Bronchiolitis Obliterans</mesh_term>
    <mesh_term>Organizing Pneumonia</mesh_term>
    <mesh_term>Wounds and Injuries</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/NCT03237364
org study id: Pro00076112
nct id: NCT03237364
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The goal of this study is to evaluate the utilization of conventional 'thermally' polarized
      perfluorinated gases mixed with oxygen as an exogenous inert contrast agent to image the
      airway spaces in subjects with suspected lung disease, post deployment in Iraq and
      Afghanistan. This is an open label proof of concept study expanding on work here at Duke.
There has been mounting evidence of respiratory problems related to military service in the
      Middle East especially in the past two decades. An overview by Flavo et al. summarizes
      studies not only of soldiers but evaluation of particulates from the Middle East in a number
      of animal models. While there have been some 'prospective' studies based on use of a standard
      evaluation protocol post deployment, the primary imaging modalities have been chest
      radiograph (most read as normal) and chest high resolution computed tomography (HRCT),
      neither of which have significant functional information. Standard pulmonary function testing
      (e.g. spirometry, lung volumes, diffusing capacity, bronchoalveolar lavage, as well as
      oscillatory resistance) were used in the STAMPEDE study, but only provide global functional
      information. The case study by King et al. included lung biopsy in a sub-cohort (n = 49) of
      soldiers with varying degrees of inhalation exposure during deployment. All biopsy samples
      were abnormal and some were consistent with constrictive bronchiolitis. Constrictive
      bronchiolitis is a non-reversible bronchiolar airway disease that is characterized by
      fibrosis of the bronchioles and can be challenging to diagnose without biopsy (it is also
      known by the term 'bronchiolitis obliterans'). The chest radiographs were normal in these
      subjects although about 25% of chest CT showed 'air trapping' or 'centrilobular nodules'.
      Pulmonary function testing in 39 soldiers with HRCT showed normal to near normal results in
      32 of the subjects, with seven showing low diffusion capacity, obstruction and/or
      restriction. Clearly, neither global measures of lung function nor high resolution anatomic
      imaging are sensitive enough to avoid a biopsy to confirm diagnosis of constrictive
      bronchiolitis. We hypothesize that measures of regional lung function should provide
      additional information to aid in the diagnosis of WLI and may assist in the management of
      more difficult or advanced cases of WLI.

      This is an open label study in up to 10 subjects being evaluated for post war lung injury.
      Each subject will receive up to 25 liters of inert perfluoropropane/oxygen gas mixtures as a
      contrast agent to visualize the airway and alveolar spaces in their lungs using 19F magnetic
      resonance imaging of inert gas/oxygen mixtures.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Lung Ventilatory Heterogeneity defined by parametric imaging with 19F perfluorinated gas/oxygen mixtures
time frame: one hour
description: Fraction of lung with slow filling compartments compared to historic norms.
intervention type: Diagnostic Test
intervention name: Perfluorinated Gas/Oxygen Mixture
description: 19-Fluorine (19F) MRI of the lungs with 21%/79% Oxygen/Perfluorinated Gas, ≤ 25 liters, gas, single visit, < 1 hour
other name: Perfluorinated Propane Imaging
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Cecil Charles, PhD
role: Principal Investigator
affiliation: Duke University Medical Center, Department of Radiology
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Hal C Charles
investigator title: Assistant Professor of Radiology
mesh term: Bronchiolitis
mesh term: Lung Injury
mesh term: Bronchiolitis Obliterans
mesh term: Organizing Pneumonia
mesh term: Wounds and Injuries
sharing ipd: No