<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/NCT02204202</url>
  </required_header>
  <id_info>
    <org_study_id>1R01HL121218-01-201102155</org_study_id>
    <secondary_id>R01HL121218</secondary_id>
    <nct_id>NCT02204202</nct_id>
  </id_info>
  <brief_title>PET Assessment of Acute Lung Transplant Rejection</brief_title>
  <official_title>Positron Emission Tomography Assessment of Acute Lung Transplant Rejection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to gain understanding of the basic responses of the&#xD;
      lungs to inflammation and specifically if there may be a better way to detect graft&#xD;
      inflammation using non-invasive methods as well as to determine the effectiveness of&#xD;
      immunosuppressive treatment regimens in preventing acute rejection in lung transplant&#xD;
      recipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Positron emission tomography with fluorodeoxyglucose (FDG-PET) is a potential way we can&#xD;
      measure lung inflammation. FDG-PET imaging is a clinically accepted and FDA-approved method&#xD;
      that is commonly used in the diagnosis and management of cancer. PET is a machine that&#xD;
      detects radiation and generates pictures using a donut shaped scanner similar in appearance&#xD;
      to an x-ray &quot;CAT&quot; computerized axial tomography or computed tomography (CT) scan. FDG stands&#xD;
      for [18F] (flourine 18) fluorodeoxyglucose, a radiolabeled sugar that is used to identify&#xD;
      areas of inflammation with the PET scanner. A CT scan takes a picture of what the lungs and&#xD;
      airways look like.&#xD;
&#xD;
      T cells are the primary cause of acute rejection of lung transplants. Because T cells must&#xD;
      divide in order to be activated and cause rejection, imaging them while they are dividing is&#xD;
      another way that we can determine whether acute rejection is occurring. A new PET tracer&#xD;
      called [18F]ISO-1 (18F-labeled σ2-receptor ligand for PET,&#xD;
      N-(4-(6,7-dimethoxy-3,-4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbe&#xD;
      nzamide (18F-3c), binds to dividing cells. Therefore, [18F]ISO-1 may help us measure acute&#xD;
      rejection more accurately. [18F]ISO-1 is an investigational drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PI left institution&#xD;
  </why_stopped>
  <start_date>February 2014</start_date>
  <completion_date type="Actual">February 4, 2017</completion_date>
  <primary_completion_date type="Actual">February 4, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung</measure>
    <time_frame>This outcome measure is assessed from the [18F]FDG scan performed on Day 1.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Logan plot analysis determined distribution volume ratio (DVR) of [18F] ISO-1 uptake</measure>
    <time_frame>This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells</measure>
    <time_frame>Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan</time_frame>
    <description>The biopsy specimens will be stained for proliferation markers. The bronchoalveolar lavage cells will be assessed for glucose uptake with 2-NBDG ( fluorescent glucose analog that has been used to monitor glucose uptake in live cells, as an indicator of cell viability).</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">28</enrollment>
  <condition>Lung Disease</condition>
  <arm_group>
    <arm_group_label>Grade A0</arm_group_label>
    <description>Double-lung transplant recipients with no evidence of rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Grades A2-3</arm_group_label>
    <description>Double-lung transplant recipients with mild to moderate rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]FDG</intervention_name>
    <description>10 millicuries (mCi) of [18F]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition</description>
    <arm_group_label>Grade A0</arm_group_label>
    <arm_group_label>Grades A2-3</arm_group_label>
    <other_name>fluorodeoxyglucose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[18F]ISO-1</intervention_name>
    <description>8 mCi of [18F]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition</description>
    <arm_group_label>Grade A0</arm_group_label>
    <arm_group_label>Grades A2-3</arm_group_label>
    <other_name>F-18 labeled proliferation tracer targeting PGRMC1</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      cells from bronchoalveolar lavage specimen; tissues from biopsy specimens&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Any patient within 7 months of double-lung transplantation and who is scheduled for&#xD;
        bronchoscopy with biopsy will be eligible. Patients will be identified via the bronchoscopy&#xD;
        schedule through the Lung Transplant Center at Barnes-Jewish Hospital / Washington&#xD;
        University School of Medicine and approached for potential participation prior to their&#xD;
        scheduled bronchoscopy. PET/CT imaging with [18F]FDG will be performed, if consented, no&#xD;
        more than 3 days after results from the biopsy are reported. [18F]ISO-1 PET/CT imaging will&#xD;
        be performed the day after [18F]FDG PET and can be performed after treatment for acute&#xD;
        rejection has been initiated. We intend to image 30 lung transplant recipients with no&#xD;
        evidence of rejection (grade A0) and 30 recipients with mild to moderate (grades A2-3)&#xD;
        rejection.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Double-lung transplant recipient&#xD;
&#xD;
          -  Scheduled for bronchoscopy with transbronchial biopsy&#xD;
&#xD;
          -  Capable of lying still and supine with arms raised above the head within the PET/CT&#xD;
             scanner for ~1.25 hours&#xD;
&#xD;
          -  Capable of following instructions for breathing protocol during CT portion of PET/CT&#xD;
&#xD;
          -  Able and willing to give informed consent&#xD;
&#xD;
          -  BMI &lt; 35&#xD;
&#xD;
          -  Already scheduled to undergo bronchoscopy with bronchoalveolar lavage (BAL) for&#xD;
             clinical reasons&#xD;
&#xD;
          -  Willing to donate a portion of BAL and biopsy specimen for laboratory testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Glucose level &gt; 150 mg/dl at time of [18F]FDG PET scan (however, up to 160 mg/dl, with&#xD;
             repeat testing showing level is stable or decreasing, is acceptable)&#xD;
&#xD;
          -  Pregnancy (confirmed by qualitative urine human chorionic gonadotropin (hCG) pregnancy&#xD;
             test)&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Presence of implanted electronic medical device&#xD;
&#xD;
          -  Enrollment in another research study of an investigational drug&#xD;
&#xD;
          -  Inability to lie flat with arms raised above the head for 1.5 hours for PET/CT scans&#xD;
             or follow breathing protocol instructions for the CT portion of the PET/CT&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Delphine L Chen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine / Barnes-Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute lung transplant rejection</keyword>
  <keyword>neutrophilic lung inflammation</keyword>
  <keyword>positron emission tomography imaging</keyword>
  <keyword>[18F] fluorodeoxyglucose</keyword>
  <keyword>[18F] ISO-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorodeoxyglucose F18</mesh_term>
  </intervention_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/NCT02204202
org study id: 1R01HL121218-01-201102155
secondary id: R01HL121218
nct id: NCT02204202
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this research study is to gain understanding of the basic responses of the
      lungs to inflammation and specifically if there may be a better way to detect graft
      inflammation using non-invasive methods as well as to determine the effectiveness of
      immunosuppressive treatment regimens in preventing acute rejection in lung transplant
      recipients.
Positron emission tomography with fluorodeoxyglucose (FDG-PET) is a potential way we can
      measure lung inflammation. FDG-PET imaging is a clinically accepted and FDA-approved method
      that is commonly used in the diagnosis and management of cancer. PET is a machine that
      detects radiation and generates pictures using a donut shaped scanner similar in appearance
      to an x-ray "CAT" computerized axial tomography or computed tomography (CT) scan. FDG stands
      for [18F] (flourine 18) fluorodeoxyglucose, a radiolabeled sugar that is used to identify
      areas of inflammation with the PET scanner. A CT scan takes a picture of what the lungs and
      airways look like.

      T cells are the primary cause of acute rejection of lung transplants. Because T cells must
      divide in order to be activated and cause rejection, imaging them while they are dividing is
      another way that we can determine whether acute rejection is occurring. A new PET tracer
      called [18F]ISO-1 (18F-labeled σ2-receptor ligand for PET,
      N-(4-(6,7-dimethoxy-3,-4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbe
      nzamide (18F-3c), binds to dividing cells. Therefore, [18F]ISO-1 may help us measure acute
      rejection more accurately. [18F]ISO-1 is an investigational drug.
observational model: Cohort
time perspective: Cross-Sectional
measure: Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung
time frame: This outcome measure is assessed from the [18F]FDG scan performed on Day 1.
measure: Logan plot analysis determined distribution volume ratio (DVR) of [18F] ISO-1 uptake
time frame: This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2.
measure: Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells
time frame: Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan
description: The biopsy specimens will be stained for proliferation markers. The bronchoalveolar lavage cells will be assessed for glucose uptake with 2-NBDG ( fluorescent glucose analog that has been used to monitor glucose uptake in live cells, as an indicator of cell viability).
arm group label: Grade A0
description: Double-lung transplant recipients with no evidence of rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans
arm group label: Grades A2-3
description: Double-lung transplant recipients with mild to moderate rejection who undergo both [18F]FDG and [18F]ISO-1 PET imaging scans
intervention type: Drug
intervention name: [18F]FDG
description: 10 millicuries (mCi) of [18F]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
arm group label: Grade A0
arm group label: Grades A2-3
other name: fluorodeoxyglucose
intervention type: Drug
intervention name: [18F]ISO-1
description: 8 mCi of [18F]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
arm group label: Grade A0
arm group label: Grades A2-3
other name: F-18 labeled proliferation tracer targeting PGRMC1
cells from bronchoalveolar lavage specimen; tissues from biopsy specimens
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Delphine L Chen, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Fluorodeoxyglucose F18