<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/NCT03300882</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT CTOT-22</org_study_id>
    <secondary_id>NIAID CRMS ID#: 38277</secondary_id>
    <nct_id>NCT03300882</nct_id>
  </id_info>
  <brief_title>PREDICT Cytomegalovirus (CMV)</brief_title>
  <acronym>PREDICT CMV</acronym>
  <official_title>Prospective Multicenter Cytomegalovirus (CMV) Specific Immune Monitoring to Predict Patient Risk After Lung Transplantation (CTOT-22)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinical Trials in Organ Transplantation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rho Federal Systems Division, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The overall objective of this study is to establish a personalized test to measure&#xD;
      individualized cytomegalovirus (CMV) specific immunity in lung transplant recipients in an&#xD;
      effort to guide antiviral prophylaxis duration in clinical practice.&#xD;
&#xD;
      Targeted participants are those:&#xD;
&#xD;
        -  enrolled in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who&#xD;
&#xD;
        -  are CMV recipient positive by serology as determined using methods in accordance with&#xD;
           current local organ procurement organization policies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cytomegalovirus (CMV) is a common virus. The virus is spread from one person to another&#xD;
      through infected body fluids. In those with a normal immune system, CMV does not cause much&#xD;
      of a problem. The immune system keeps the virus under control so most people do not have any&#xD;
      symptoms. Once infected, the virus usually stays dormant (inactive) in the body for a&#xD;
      person's entire life. This means some of the cells in the body are infected and the virus can&#xD;
      become active again.&#xD;
&#xD;
      Lung transplant recipients take anti-rejection medicines to prevent the body from rejecting&#xD;
      the transplanted lung(s). Although anti-rejection medications help protect the transplanted&#xD;
      lung(s) from the body's immune system, these medications also decrease the body's ability to&#xD;
      fight infections. This reduces the immune system's ability to control viruses like CMV. Many&#xD;
      transplant recipients take an antiviral medication early after transplant to help the body&#xD;
      control the CMV virus. This is the time that risk of infection would be highest. Sometimes&#xD;
      recipients get an active CMV infection after stopping these medicines. If this happens, the&#xD;
      infection is treated and monitored.&#xD;
&#xD;
      In this study, investigators are trying to determine whether a blood test can predict&#xD;
      development of active CMV infection in lung transplant recipients. Specifically, the clinical&#xD;
      research study will prospectively assess the performance of an immune signature based on the&#xD;
      &quot;ex vivo&quot; measurement of T cell CMV specific immunity in predicting freedom from future CMV&#xD;
      infections among recipient positive (R+) lung transplant participants receiving standard&#xD;
      durations of valganciclovir prophylaxis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2017</start_date>
  <completion_date type="Actual">November 25, 2019</completion_date>
  <primary_completion_date type="Actual">November 25, 2019</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease within 6 months Post CMV Prophylaxis Discontinuation</measure>
    <time_frame>From CMV Prophylaxis Discontinuation to 6 Months Post CMV Prophylaxis Discontinuation</time_frame>
    <description>Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease Within 18 Months Post-Transplant</measure>
    <time_frame>From CMV Prophylaxis Discontinuation to 18-Months Post-Transplant</time_frame>
    <description>Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">84</enrollment>
  <condition>Lung Transplant</condition>
  <arm_group>
    <arm_group_label>CMV+ First Lung Transplant Recipients</arm_group_label>
    <description>Participants enrolled in one of four North American sites in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who are cytomegalovirus positive by serology (e.g., CMV Recipient positive).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Procedure</intervention_name>
    <description>Serial blood draws. Participants will be enrolled either pre-transplant or within 45 days post-transplant and will be followed over the course of 18 months post transplant. Protocol mandated serial measurement of cytomegalovirus (CMV)-specific immune signature will occur pre-transplant (as applicable) and at post-transplant timepoint months 2, -3, -6, -9, -12 and -18.</description>
    <arm_group_label>CMV+ First Lung Transplant Recipients</arm_group_label>
    <other_name>Serial blood draws</other_name>
    <other_name>Phlebotomy</other_name>
    <other_name>Venipuncture</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood mononuclear cells (PBMCs) and plasma.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult lung transplant recipients undergoing lung transplant at one of the four&#xD;
        participating centers and concurrently enrolled in CTOT-20 (Clinical Trials.gov ID:&#xD;
        NCT02631720).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Individuals who meet all of the following criteria are eligible for enrollment as study&#xD;
        participants:&#xD;
&#xD;
          -  Must be able to understand and provide written informed consent;&#xD;
&#xD;
          -  Anticipated listing for lung transplantation OR listed for lung transplant OR is&#xD;
             within 45 days of having received a single or bilateral cadaveric donor lung&#xD;
             transplant;&#xD;
&#xD;
          -  Undergoing first lung transplant operation;&#xD;
&#xD;
          -  Transplant surgery to be performed or performed at enrolling center;&#xD;
&#xD;
          -  Concurrent participation in CTOT-20 (Clinical Trials.gov ID: NCT02631720); and&#xD;
&#xD;
          -  CMV-seropositive lung transplant recipient, using methods in accordance with current&#xD;
             local organ procurement organization policies.&#xD;
&#xD;
               -  Note: Concurrent participation in immune monitoring studies or interventional&#xD;
                  device trials are permitted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Individuals who meet any of the following criteria are not eligible for enrollment as study&#xD;
        participants:&#xD;
&#xD;
          -  Unwilling to enroll in CTOT-20 (Clinical Trials.gov ID: NCT02631720);&#xD;
&#xD;
          -  Multi-organ recipient;&#xD;
&#xD;
          -  Prior recipient of any solid organ transplant, including prior lung transplant;&#xD;
&#xD;
          -  Prior or concurrent recipient of bone marrow transplant;&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV) infection;&#xD;
&#xD;
          -  Pregnant or planned pregnancy;&#xD;
&#xD;
          -  Any condition that, in the investigator's opinion, would make it unlikely for the&#xD;
             recipient to complete follow up procedures or complete the study; or&#xD;
&#xD;
          -  Participation in an investigational drug trial at the time of enrollment visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laurie Snyder, MD, MHS</last_name>
    <role>Study Chair</role>
    <affiliation>Duke University Medical Center: Transplantation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Scott Palmer, MD, MHS</last_name>
    <role>Study Chair</role>
    <affiliation>Duke University Medical Center: Transplantation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Hospital: Transplantation</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center: Transplantation</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation: Transplantation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto General Hospital: Transplantation</name>
      <address>
        <city>Toronto</city>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.niaid.nih.gov</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID)</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/about/dait</url>
    <description>Division of Allergy, Immunology, and Transplantation (DAIT)</description>
  </link>
  <link>
    <url>http://www.ctotstudies.org/</url>
    <description>Clinical Trials in Organ Transplantation (CTOT)</description>
  </link>
  <reference>
    <citation>Snyder LD, Chan C, Kwon D, Yi JS, Martissa JA, Copeland CA, Osborne RJ, Sparks SD, Palmer SM, Weinhold KJ. Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78-85. doi: 10.1164/rccm.201504-0733OC.</citation>
    <PMID>26372850</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Study co-enrollment (CTOT-20 and CTOT-22)</keyword>
  <keyword>cytomegalovirus (CMV)</keyword>
  <keyword>CMV seropositive positive recipient</keyword>
  <keyword>CMV infection</keyword>
  <keyword>CMV-specific immunity</keyword>
  <keyword>immunologic monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytomegalovirus Infections</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/NCT03300882
org study id: DAIT CTOT-22
secondary id: NIAID CRMS ID#: 38277
nct id: NCT03300882
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The overall objective of this study is to establish a personalized test to measure
      individualized cytomegalovirus (CMV) specific immunity in lung transplant recipients in an
      effort to guide antiviral prophylaxis duration in clinical practice.

      Targeted participants are those:

        -  enrolled in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who

        -  are CMV recipient positive by serology as determined using methods in accordance with
           current local organ procurement organization policies.
Cytomegalovirus (CMV) is a common virus. The virus is spread from one person to another
      through infected body fluids. In those with a normal immune system, CMV does not cause much
      of a problem. The immune system keeps the virus under control so most people do not have any
      symptoms. Once infected, the virus usually stays dormant (inactive) in the body for a
      person's entire life. This means some of the cells in the body are infected and the virus can
      become active again.

      Lung transplant recipients take anti-rejection medicines to prevent the body from rejecting
      the transplanted lung(s). Although anti-rejection medications help protect the transplanted
      lung(s) from the body's immune system, these medications also decrease the body's ability to
      fight infections. This reduces the immune system's ability to control viruses like CMV. Many
      transplant recipients take an antiviral medication early after transplant to help the body
      control the CMV virus. This is the time that risk of infection would be highest. Sometimes
      recipients get an active CMV infection after stopping these medicines. If this happens, the
      infection is treated and monitored.

      In this study, investigators are trying to determine whether a blood test can predict
      development of active CMV infection in lung transplant recipients. Specifically, the clinical
      research study will prospectively assess the performance of an immune signature based on the
      "ex vivo" measurement of T cell CMV specific immunity in predicting freedom from future CMV
      infections among recipient positive (R+) lung transplant participants receiving standard
      durations of valganciclovir prophylaxis.
observational model: Cohort
time perspective: Prospective
measure: Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease within 6 months Post CMV Prophylaxis Discontinuation
time frame: From CMV Prophylaxis Discontinuation to 6 Months Post CMV Prophylaxis Discontinuation
description: Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.
measure: Time from CMV Prophylaxis Discontinuation Post-Transplant to First Detection of CMV Infection or CMV Disease Within 18 Months Post-Transplant
time frame: From CMV Prophylaxis Discontinuation to 18-Months Post-Transplant
description: Participants will be evaluated for CMV infection or disease according to each center's standard of care clinical protocol. All centers have aligned their clinical practice to include, at a minimum, a CMV infection and a CMV disease assessment at the time of prophylaxis discontinuation, monthly for the first 6 months after discontinuation, and quarterly after that up to 18 months post transplantation.
arm group label: CMV+ First Lung Transplant Recipients
description: Participants enrolled in one of four North American sites in clinical research study CTOT-20 (Clinical Trials.gov ID: NCT02631720) who are cytomegalovirus positive by serology (e.g., CMV Recipient positive).
intervention type: Other
intervention name: Procedure
description: Serial blood draws. Participants will be enrolled either pre-transplant or within 45 days post-transplant and will be followed over the course of 18 months post transplant. Protocol mandated serial measurement of cytomegalovirus (CMV)-specific immune signature will occur pre-transplant (as applicable) and at post-transplant timepoint months 2, -3, -6, -9, -12 and -18.
arm group label: CMV+ First Lung Transplant Recipients
other name: Serial blood draws
other name: Phlebotomy
other name: Venipuncture
Peripheral blood mononuclear cells (PBMCs) and plasma.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laurie Snyder, MD, MHS
role: Study Chair
affiliation: Duke University Medical Center: Transplantation
last name: Scott Palmer, MD, MHS
role: Study Chair
affiliation: Duke University Medical Center: Transplantation
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
url: https://www.niaid.nih.gov
description: National Institute of Allergy and Infectious Diseases (NIAID)
url: https://www.niaid.nih.gov/about/dait
description: Division of Allergy, Immunology, and Transplantation (DAIT)
url: http://www.ctotstudies.org/
description: Clinical Trials in Organ Transplantation (CTOT)
citation: Snyder LD, Chan C, Kwon D, Yi JS, Martissa JA, Copeland CA, Osborne RJ, Sparks SD, Palmer SM, Weinhold KJ. Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78-85. doi: 10.1164/rccm.201504-0733OC.
PMID: 26372850
responsible party type: Sponsor
mesh term: Cytomegalovirus Infections