Clincosm LogoSign in Get a demo

BA: Mapping Disease Pathways for Biliary Atresia

Sponsor
University of Pittsburgh (Other)
Overall Status
Recruiting
CT.gov ID
NCT03273049
Collaborator
National Institutes of Health (NIH) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
1,100
Enrollment
1
Location
84
Anticipated Duration (Months)
13.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    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.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    1100 participants
    Observational Model:
    Other
    Time Perspective:
    Prospective
    Official Title:
    Coordinating Center- Mapping Disease Pathways for Biliary Atresia
    Actual Study Start Date :
    Jul 21, 2016
    Anticipated Primary Completion Date :
    Dec 21, 2022
    Anticipated Study Completion Date :
    Jul 21, 2023

    Outcome Measures

    Primary Outcome Measures

    1. Genomic pathways of BA [up to two years]

      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.

    Secondary Outcome Measures

    1. Predisposition of BA [upwards of four years to achieve this outcome measure]

      determine whether candidate genes and related pathways which predispose to BA, also predispose to laterality defects affecting the liver and other organs.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • living individuals who were diagnosed with Biliary Atresia and received or are about to receive a liver transplant from multiple participating centers (Children's Hospital of Pittsburgh, Kings College Hospital, Children's Hospital of Birmingham, and Hospital Sírio-Libanês).
    Exclusion Criteria:
    • No child participant in the care of the state will be enrolled, nor will patients in the care of temporary or informal guardians be enrolled

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224

    Sponsors and Collaborators

    • University of Pittsburgh
    • National Institutes of Health (NIH)
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rakesh Sindhi, Rakesh Sindhi, MD, Professor of Surgery, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03273049
    Other Study ID Numbers:
    • STUDY19070273
    • 1R01DK109365-01A1
    First Posted:
    Sep 6, 2017
    Last Update Posted:
    May 3, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Biliary Atresia

    Study Results

    No Results Posted as of May 3, 2022