xml: <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/NCT06012500</url>
    </required_header>
    <id_info>
      <org_study_id>2021-0031</org_study_id>
      <nct_id>NCT06012500</nct_id>
    </id_info>
    <brief_title>Evaluation of Explanted Lungs by MRI and Biological Assays</brief_title>
    <acronym>Xe MRI in ILD</acronym>
    <official_title>Evaluation of Explanted Lungs by MRI and Biological Assays</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Children's Hospital Medical Center, Cincinnati</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Children's Hospital Medical Center, Cincinnati</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 purpose of this multi-centered, NIH-sponsored study is to to develop an optimal protocol&#xD;
        for using non-invasive 129Xe gas exchange MRI to detect changing disease activity in&#xD;
        interstitial lung diseases (ILDs). We base this study on the demonstrated promise of 129Xe as&#xD;
        a biomarker for both prognosis and therapy response, overwhelming interest from both industry&#xD;
        and academic partners, and impending FDA approval for 129Xe ventilation MRI. This requires&#xD;
        disseminating standardized and repeatable methods for 3D 129Xe functional MRI in order to&#xD;
        facilitate innovative multi-center observational and interventional trials that can advance&#xD;
        our understanding of fibrotic lung disease, while accelerating the development of novel&#xD;
        therapies.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        There remains an urgent need to better phenotype interstitial lung diseases, predict&#xD;
        trajectories, monitor progression, and measure treatment response. Because ILD pathology is&#xD;
        spatially and temporarly heterogeneous, the problem demands a 3-dimensional (3D) lung&#xD;
        assessment. To this end, CT imaging patterns are critical in IPF diagnosis, but such&#xD;
        structural imaging is insensitive to changing functional status. Thus, we have developed&#xD;
        hyperpolarized (HP) 129Xe MRI, whose unique properties enable rapid, non-invasive, 3D&#xD;
        functional assessment of inhaled gas distribu-tion in the airspaces, as well as its uptake in&#xD;
        the pulmonary interstitium (barrier tissues) and trans-fer to the pulmonary capillary red&#xD;
        blood cells (RBCs). This way of probing regional gas exchange confers sensitivity to&#xD;
        micron-scale interstitial barrier thickening and locally diminished RBC trans-fer. We have&#xD;
        used 129Xe MRI to predict outcomes such as death or the need for transplant and have provided&#xD;
        preliminary evidence showing that barrier uptake is a sensitive and early marker of therapy&#xD;
        response. These advancements have led to demands for wider dissemination, which drives an&#xD;
        urgent need to harmonize acquisition protocols and quantification methods.&#xD;
  &#xD;
        This work will be conducted by 4 collaborating centers - Duke University, the University of&#xD;
        Cin-cinnati, Cincinnati Children's Hospital Medical Center, and the University of Wisconsin.&#xD;
        Cincin-nati Children's will operate under its own IRB protocol and IND, but each will share&#xD;
        data and im-aging techniques in order to establish best practices. The specific aims of the&#xD;
        work are:&#xD;
  &#xD;
        Aim 1 - Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms. We&#xD;
        will improve upon published repeatability of ±15-20% by harmonizing MRI/MRS protocols by&#xD;
        improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the&#xD;
        individ-ual patient. Using these approaches, each center will demonstrate coefficients of&#xD;
        repeatability of ±6% or better in patients with ILD.&#xD;
  &#xD;
        Aim 2 - Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS. We will deploy a&#xD;
        reconstruction and analysis package enabling users of any of three major MRI vendor&#xD;
        plat-forms to obtain robust, real-time quantitative analysis of images and spectra. We will&#xD;
        demon-strate that healthy reference cohorts are equivalent to ±10% across 4 centers and use&#xD;
        this to build the definitive multi-site healthy reference distributions.&#xD;
  &#xD;
        Aim 3 - Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging. To position&#xD;
        the technology for clinical deployment and interpretation, we will develop a physiologic&#xD;
        model incorporating ventilation, barrier and RBC metrics to explain the underlying factors&#xD;
        responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO).&#xD;
        This framework will be deployed to readers who will differentiate ILD from normal aging.&#xD;
  &#xD;
        The expected outcomes are to 1) deploy robust and standardized acquisition and analysis&#xD;
        proto-cols across centers and scanner platforms, 2) establish the methods and standards for&#xD;
        maximiz-ing repeatability of each gas exchange imaging metric, and 3) provide the tools and&#xD;
        framework needed to use 129Xe MRI to characterize disease and assess therapeutic efficacy.&#xD;
        Collectively, this program will enable rapid and innovative trials that will accelerate&#xD;
        progress in studying and treating fibrotic lung disease. While this technical development&#xD;
        study is focused on healthy sub-jects and those with ILD, deployment of these non-invasive&#xD;
        MRI methods should benefit the study of interstitial lung disease more broadly, as well as&#xD;
        other conditions of gas exchange im-pairment such as pulmonary vascular disease, COPD, and&#xD;
        COVID-19.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 14, 2022</start_date>
    <completion_date type="Anticipated">March 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms</measure>
      <time_frame>1 day</time_frame>
      <description>Harmonize MRI/MRS protocols by improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the individual patient. Using these approaches, each center will demonstrate coefficients of repeatability of ±6% or better in patients with ILD.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS</measure>
      <time_frame>1 day</time_frame>
      <description>Deploy a reconstruction and analysis package enabling users of any of three major MRI vendor platforms to obtain robust, real-time quantitative analysis of images and spectra.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging</measure>
      <time_frame>1 Day</time_frame>
      <description>To position the technology for clinical deployment and interpretation, we will develop a physiologic model incorporating ventilation, barrier and RBC metrics to explain the underlying factors responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO)</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>ILD</condition>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <description>Healthy Controls</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ILD</arm_group_label>
      <description>Participants with diagnosed ILD</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Xenon-129</intervention_name>
      <description>Inhaled contrast for MRI</description>
      <arm_group_label>Control</arm_group_label>
      <arm_group_label>ILD</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          - Patients with ILD and healthy controls&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#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. Clinical diagnosis of Interstitial Lung Disease made by a board certified&#xD;
               pulmonologist us-ing established criteria. We will not exclude individuals based on&#xD;
               ILD type or severity of disease with the exception of the below criteria&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Subject is less than 18 years old&#xD;
  &#xD;
            2. MRI is contraindicated based on responses to MRI screening questionnaire&#xD;
  &#xD;
            3. Subject is pregnant or lactating&#xD;
  &#xD;
            4. Resting oxygen saturation on room air &lt;90%&#xD;
  &#xD;
            5. Respiratory illness of a bacterial or viral etiology within 30 days of MRI&#xD;
  &#xD;
            6. Subject has history of any known ventricular cardiac arrhythmia&#xD;
  &#xD;
            7. Subject has history of cardiac arrest within the last year&#xD;
  &#xD;
            8. Subject does not fit into 129Xe vest coil used for MRI&#xD;
  &#xD;
            9. Subject cannot hold his/her breath for 15 seconds&#xD;
  &#xD;
           10. Subject deemed unlikely to be able to comply with instructions during imaging&#xD;
  &#xD;
           11. Medical or psychological conditions which, in the opinion of the investigator, might&#xD;
               create undue risk to the subject or interfere with the subject's ability to comply&#xD;
               with the protocol requirements&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Jason Woods, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ashley Bordon, MS</last_name>
      <phone>513-636-0143</phone>
      <email>Ashley.Bordon@cchmc.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jason Woods, PhD</last_name>
      <phone>513-803-4463</phone>
      <email>Jason.Woods@cchmc.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Cincinnati Children's Hospital Medical Center</name>
        <address>
          <city>Cincinnati</city>
          <state>Ohio</state>
          <zip>45229</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jason Woods, PhD</last_name>
        <phone>513-803-4463</phone>
        <email>Jason.Woods@cchmc.org</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>September 3, 2021</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Xenon</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06012500
  org study id: 2021-0031
  nct id: NCT06012500
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this multi-centered, NIH-sponsored study is to to develop an optimal protocol
        for using non-invasive 129Xe gas exchange MRI to detect changing disease activity in
        interstitial lung diseases (ILDs). We base this study on the demonstrated promise of 129Xe as
        a biomarker for both prognosis and therapy response, overwhelming interest from both industry
        and academic partners, and impending FDA approval for 129Xe ventilation MRI. This requires
        disseminating standardized and repeatable methods for 3D 129Xe functional MRI in order to
        facilitate innovative multi-center observational and interventional trials that can advance
        our understanding of fibrotic lung disease, while accelerating the development of novel
        therapies.
  There remains an urgent need to better phenotype interstitial lung diseases, predict
        trajectories, monitor progression, and measure treatment response. Because ILD pathology is
        spatially and temporarly heterogeneous, the problem demands a 3-dimensional (3D) lung
        assessment. To this end, CT imaging patterns are critical in IPF diagnosis, but such
        structural imaging is insensitive to changing functional status. Thus, we have developed
        hyperpolarized (HP) 129Xe MRI, whose unique properties enable rapid, non-invasive, 3D
        functional assessment of inhaled gas distribu-tion in the airspaces, as well as its uptake in
        the pulmonary interstitium (barrier tissues) and trans-fer to the pulmonary capillary red
        blood cells (RBCs). This way of probing regional gas exchange confers sensitivity to
        micron-scale interstitial barrier thickening and locally diminished RBC trans-fer. We have
        used 129Xe MRI to predict outcomes such as death or the need for transplant and have provided
        preliminary evidence showing that barrier uptake is a sensitive and early marker of therapy
        response. These advancements have led to demands for wider dissemination, which drives an
        urgent need to harmonize acquisition protocols and quantification methods.
  
        This work will be conducted by 4 collaborating centers - Duke University, the University of
        Cin-cinnati, Cincinnati Children's Hospital Medical Center, and the University of Wisconsin.
        Cincin-nati Children's will operate under its own IRB protocol and IND, but each will share
        data and im-aging techniques in order to establish best practices. The specific aims of the
        work are:
  
        Aim 1 - Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms. We
        will improve upon published repeatability of ±15-20% by harmonizing MRI/MRS protocols by
        improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the
        individ-ual patient. Using these approaches, each center will demonstrate coefficients of
        repeatability of ±6% or better in patients with ILD.
  
        Aim 2 - Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS. We will deploy a
        reconstruction and analysis package enabling users of any of three major MRI vendor
        plat-forms to obtain robust, real-time quantitative analysis of images and spectra. We will
        demon-strate that healthy reference cohorts are equivalent to ±10% across 4 centers and use
        this to build the definitive multi-site healthy reference distributions.
  
        Aim 3 - Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging. To position
        the technology for clinical deployment and interpretation, we will develop a physiologic
        model incorporating ventilation, barrier and RBC metrics to explain the underlying factors
        responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO).
        This framework will be deployed to readers who will differentiate ILD from normal aging.
  
        The expected outcomes are to 1) deploy robust and standardized acquisition and analysis
        proto-cols across centers and scanner platforms, 2) establish the methods and standards for
        maximiz-ing repeatability of each gas exchange imaging metric, and 3) provide the tools and
        framework needed to use 129Xe MRI to characterize disease and assess therapeutic efficacy.
        Collectively, this program will enable rapid and innovative trials that will accelerate
        progress in studying and treating fibrotic lung disease. While this technical development
        study is focused on healthy sub-jects and those with ILD, deployment of these non-invasive
        MRI methods should benefit the study of interstitial lung disease more broadly, as well as
        other conditions of gas exchange im-pairment such as pulmonary vascular disease, COPD, and
        COVID-19.
  observational model: Case-Only
  time perspective: Prospective
  measure: Maximize and Measure Repeatability of 129Xe MRI/MRS Metrics across MRI Platforms
  time frame: 1 day
  description: Harmonize MRI/MRS protocols by improved coaching, optimized dose delivery, and tailoring the inhaled dose volume to the individual patient. Using these approaches, each center will demonstrate coefficients of repeatability of ±6% or better in patients with ILD.
  measure: Establish Harmonized Quantitative Analysis of Gas Exchange MRI/MRS
  time frame: 1 day
  description: Deploy a reconstruction and analysis package enabling users of any of three major MRI vendor platforms to obtain robust, real-time quantitative analysis of images and spectra.
  measure: Deploy a Clinical Framework to Identify Active Fibrosis and Normal Aging
  time frame: 1 Day
  description: To position the technology for clinical deployment and interpretation, we will develop a physiologic model incorporating ventilation, barrier and RBC metrics to explain the underlying factors responsible for a given patient's diffusing capacity (DLCO) and transfer coefficient (KCO)
  arm group label: Control
  description: Healthy Controls
  arm group label: ILD
  description: Participants with diagnosed ILD
  intervention type: Drug
  intervention name: Xenon-129
  description: Inhaled contrast for MRI
  arm group label: Control
  arm group label: ILD
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 99 Years
  last name: Jason Woods, PhD
  role: Principal Investigator
  affiliation: Children's Hospital Medical Center, Cincinnati
  last name: Ashley Bordon, MS
  phone: 513-636-0143
  email: Ashley.Bordon@cchmc.org
  last name: Jason Woods, PhD
  phone: 513-803-4463
  email: Jason.Woods@cchmc.org
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Xenon
  sharing ipd: No