Mapping Disease Pathways for Biliary Atresia (BA)

September 5, 2025 updated by: Rakesh Sindhi, University of Pittsburgh

Coordinating Center- Mapping Disease Pathways for Biliary Atresia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • UPMC Children's Hospital of Pittsburgh
        • Contact:
        • Principal Investigator:
          • Rakesh Sindhi, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Individuals who have had a liver transplantation due to a diagnosis of biliary atresia.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pittsburgh

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health (NIH)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 21, 2016

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 21, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 21, 2035

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 1, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 9, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY19070273
  • 1R01DK109365-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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