- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03273049
Mapping Disease Pathways for Biliary Atresia (BA)
Coordinating Center- Mapping Disease Pathways for Biliary Atresia
Study Overview
Status
Conditions
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Morgan L Paul, BSN
- Phone Number: 4126928472
- Email: Morgan.Paul2@upmc.edu
Study Contact Backup
- Name: Daniel Pieratt, MPA
- Phone Number: 4126926692
- Email: pierattdw@upmc.edu
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- UPMC Children's Hospital of Pittsburgh
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Contact:
- Morgan L Paul, BSN
- Phone Number: 412-692-8472
- Email: Morgan.Paul2@upmc.edu
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Principal Investigator:
- Rakesh Sindhi, MD
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Contact:
- Daniel Pieratt, MPA
- Phone Number: 4126926692
- Email: pierattdw@upmc.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genomic pathways of BA
Time Frame: 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.
|
up to two years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Predisposition of BA
Time Frame: 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.
|
upwards of four years to achieve this outcome measure
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY19070273
- 1R01DK109365-01A1 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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