<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/NCT03273049</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY19070273</org_study_id>
    <secondary_id>1R01DK109365-01A1</secondary_id>
    <nct_id>NCT03273049</nct_id>
  </id_info>
  <brief_title>Mapping Disease Pathways for Biliary Atresia</brief_title>
  <acronym>BA</acronym>
  <official_title>Coordinating Center- Mapping Disease Pathways for Biliary Atresia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</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>
      This project will primarily evaluate the developmental/genetic basis of biliary atresia, the&#xD;
      most common cause of liver failure at birth, and which accounts of half of all liver&#xD;
      transplants performed worldwide in children.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Characterized by failure to drain bile from the liver due to atretic extrahepatic bile ducts,&#xD;
      BA is corrected in less than half of all affected children with surgical reconstruction. The&#xD;
      remainder progress to cirrhosis and require liver transplantation. Because bile duct loss can&#xD;
      be accompanied by other birth defects such as laterality defects of the gut and&#xD;
      cardiovascular systems, the disease has been categorized into the more common 'isolated'&#xD;
      variety presumably due to a perinatal viral cholangitis, and the 'syndromic' variety, due to&#xD;
      genetic factors. Mechanistic differences implied by this categorization have not been&#xD;
      demonstrated conclusively. In contrast, three susceptibility genes identified in&#xD;
      predominantly 'isolated&quot; BA cases, and the presence of abnormal cilia which are known to&#xD;
      predispose to laterality defects, in both isolated and syndromic forms of BA suggest that in&#xD;
      addition to environmental influences, genetic susceptibility is important in both forms of&#xD;
      BA. This view is reinforced by our preliminary work which shows that knockdown of a novel BA&#xD;
      susceptibility gene causes both biliary dysgenesis and laterality defects in animal models.&#xD;
      This finding also suggests that common birth defects affecting the liver and other organs may&#xD;
      originate from defects in the same genes. The project will combine candidate gene&#xD;
      identification and replication with human DNA samples from 1100 BA subjects and their&#xD;
      biological parents or siblings, if available, with validation using corresponding human BA&#xD;
      liver tissue and zebrafish knockdown models.&#xD;
&#xD;
      The project outcome will consist of pathways comprising multiple susceptibility genes&#xD;
      involved in morphogenesis of the liver and other organs, which explain the complex phenotype&#xD;
      of BA. The project will use the experimental and bioinformatics capabilities of the&#xD;
      Universities of Pittsburgh and California (at San Diego) to analyze data and study human&#xD;
      samples from the participating centers. Four of the world's largest pediatric liver&#xD;
      transplant centers, the Children's Hospitals of Pittsburgh (CHP), King's College Hospital&#xD;
      (KCH), London, UK, Birmingham Children's Hospital, UK (BCH), and the Hospital Sirio Libanes&#xD;
      (HSL), Sao Paulo, Brazil will enroll biliary atresia subjects and their biological parents&#xD;
      and/or siblings, if available.&#xD;
&#xD;
      Information developed in this project will be the basis for designing novel management&#xD;
      strategies to reduce the societal impact of this rare childhood disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 21, 2016</start_date>
  <completion_date type="Anticipated">July 21, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 21, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Genomic pathways of BA</measure>
    <time_frame>up to two years</time_frame>
    <description>Main project outcome will consist of pathways comprising multiple susceptibility genes involved in morphogenesis of the liver and other organs, which explain the complex phenotype of BA.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Predisposition of BA</measure>
    <time_frame>upwards of four years to achieve this outcome measure</time_frame>
    <description>determine whether candidate genes and related pathways which predispose to BA, also predispose to laterality defects affecting the liver and other organs.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">1100</enrollment>
  <condition>Biliary Atresia</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Samples with DNA: blood, saliva or liver tissue.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals who have had a liver transplantation due to a diagnosis of biliary atresia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  living individuals who were diagnosed with Biliary Atresia and received or are about&#xD;
             to receive a liver transplant from multiple participating centers (Children's Hospital&#xD;
             of Pittsburgh, Kings College Hospital, Children's Hospital of Birmingham, and Hospital&#xD;
             Sírio-Libanês).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No child participant in the care of the state will be enrolled, nor will patients in&#xD;
             the care of temporary or informal guardians be enrolled&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Morgan L Paul, BSN</last_name>
    <phone>4126928472</phone>
    <email>Morgan.Paul2@upmc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Daniel Pieratt, MPA</last_name>
    <phone>4126926692</phone>
    <email>pierattdw@upmc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UPMC Children's Hospital of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Morgan L Paul, BSN</last_name>
      <phone>412-692-8472</phone>
      <email>Morgan.Paul2@upmc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Daniel Pieratt, MPA</last_name>
      <phone>4126926692</phone>
      <email>pierattdw@upmc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Rakesh Sindhi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Rakesh Sindhi</investigator_full_name>
    <investigator_title>Rakesh Sindhi, MD, Professor of Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biliary Atresia</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/NCT03273049
org study id: STUDY19070273
secondary id: 1R01DK109365-01A1
nct id: NCT03273049
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This project will primarily evaluate the developmental/genetic basis of biliary atresia, the
      most common cause of liver failure at birth, and which accounts of half of all liver
      transplants performed worldwide in children.
Characterized by failure to drain bile from the liver due to atretic extrahepatic bile ducts,
      BA is corrected in less than half of all affected children with surgical reconstruction. The
      remainder progress to cirrhosis and require liver transplantation. Because bile duct loss can
      be accompanied by other birth defects such as laterality defects of the gut and
      cardiovascular systems, the disease has been categorized into the more common 'isolated'
      variety presumably due to a perinatal viral cholangitis, and the 'syndromic' variety, due to
      genetic factors. Mechanistic differences implied by this categorization have not been
      demonstrated conclusively. In contrast, three susceptibility genes identified in
      predominantly 'isolated" BA cases, and the presence of abnormal cilia which are known to
      predispose to laterality defects, in both isolated and syndromic forms of BA suggest that in
      addition to environmental influences, genetic susceptibility is important in both forms of
      BA. This view is reinforced by our preliminary work which shows that knockdown of a novel BA
      susceptibility gene causes both biliary dysgenesis and laterality defects in animal models.
      This finding also suggests that common birth defects affecting the liver and other organs may
      originate from defects in the same genes. The project will combine candidate gene
      identification and replication with human DNA samples from 1100 BA subjects and their
      biological parents or siblings, if available, with validation using corresponding human BA
      liver tissue and zebrafish knockdown models.

      The project outcome will consist of pathways comprising multiple susceptibility genes
      involved in morphogenesis of the liver and other organs, which explain the complex phenotype
      of BA. The project will use the experimental and bioinformatics capabilities of the
      Universities of Pittsburgh and California (at San Diego) to analyze data and study human
      samples from the participating centers. Four of the world's largest pediatric liver
      transplant centers, the Children's Hospitals of Pittsburgh (CHP), King's College Hospital
      (KCH), London, UK, Birmingham Children's Hospital, UK (BCH), and the Hospital Sirio Libanes
      (HSL), Sao Paulo, Brazil will enroll biliary atresia subjects and their biological parents
      and/or siblings, if available.

      Information developed in this project will be the basis for designing novel management
      strategies to reduce the societal impact of this rare childhood disease.
observational model: Other
time perspective: Prospective
measure: Genomic pathways of BA
time frame: up to two years
description: Main project outcome will consist of pathways comprising multiple susceptibility genes involved in morphogenesis of the liver and other organs, which explain the complex phenotype of BA.
measure: Predisposition of BA
time frame: upwards of four years to achieve this outcome measure
description: determine whether candidate genes and related pathways which predispose to BA, also predispose to laterality defects affecting the liver and other organs.
Samples with DNA: blood, saliva or liver tissue.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Morgan L Paul, BSN
phone: 4126928472
email: Morgan.Paul2@upmc.edu
last name: Daniel Pieratt, MPA
phone: 4126926692
email: pierattdw@upmc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Rakesh Sindhi
investigator title: Rakesh Sindhi, MD, Professor of Surgery
mesh term: Biliary Atresia