Intestinal Microbiome Composition in Infants With Biliary Atresia (BA) (BA)

January 22, 2023 updated by: Jorge Bezerra. MD, Children's Hospital Medical Center, Cincinnati

Intestinal Microbiome Composition in Infants With Biliary Atresia

A prospective observational study in infants with biliary atresia and controls to determine whether the composition of the intestinal microbiome is specific for biliary atresia will be conducted.

The hypothesis of the study is "infants with biliary atresia have a unique microbiome signature at the time of diagnosis and changes in population dynamics occur during disease progression". The microbiome will be determined at diagnosis and at well-defined time points during the natural history of the disease.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Biliary atresia, the most common cause of neonatal cholestasis, results from a fibrosing and inflammatory obstruction of extrahepatic bile ducts of unknown etiology. Infants with neonatal cholestasis will be enrolled at the time of diagnosis. Those that undergo exploratory laparotomy and are diagnosed with biliary atresia will form the "biliary atresia".

The development of the normal bacterial flora is a dynamic process that varies in early postnatal ages and may be influenced by disease states. To control for age differences, the composition of the microbiome in subjects with other causes of neonatal liver diseases (non-biliary atresia or disease-controls) and age-matched healthy subjects (normal controls) will be determined.

Subjects with biliary atresia will be enrolled at diagnosis, at which time a stool sample and a 2 mL blood sample will be obtained. Thereafter, a stool sample will be obtained at 3±1 months after hepatoportoenterostomy (HPE) and at 24±6 months of age. A stool sample and a 2 ml blood sample will also be obtained if/when subjects are admitted to the hospital for an evaluation and treatment of presumed infection (example: ascending cholangitis) and at the time of liver transplantation.

Similar samples will also be obtained from healthy subjects (normal controls) and patients diagnosed with other cholestatic syndromes (non-biliary atresia or disease-controls) at ages that match those of subjects with biliary atresia. Samples will be used for bacterial DNA isolation, which will be used for bacterial and mammalian gene sequencing using next-generation sequencing methods, followed by statistical analysis to identify unique microbiome compositions or alterations that are associated with particular disease (biliary atresia or non-BA controls) or clinical outcomes including response to HPE, ascending cholangitis and progression of liver disease.

Study Type

Observational

Enrollment (Anticipated)

50

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 Backup

Study Locations

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

Ages Eligible for Study

1 day to 2 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Biliary atresia, the most common cause of neonatal cholestasis, results from a fibrosing and inflammatory obstruction of extrahepatic bile ducts of unknown etiology. Infants with neonatal cholestases due to other causes and age-matched healthy controls will be enrolled.

This is a prospective study that starts at the time of evaluation of neonatal cholestasis and will collect samples and clinical data during the progression of liver disease. A subject will be eligible for study once it is determined that the subject meets entry criteria either into the study or disease-control cohorts or the normal control cohort.

Description

Inclusion Criteria:

  1. Age:

    -Birth to 5 months

  2. Disease state: Must meet either (a), (b), or (c) for eligibility.

    a) Biliary atresia:

    • Conjugated hyperbilirubinemia (serum direct bilirubin > 1mg/dL) AND demonstration of obstruction of extra hepatic bile ducts by examination of histological sections of extra hepatic bile ducts

      b) Neonatal cholestasis secondary to other causes of liver disease:

    • Diagnosis of liver disease caused by syndromes of intrahepatic cholestasis with or without hyperbilirubinemia

      c) Normal controls:

    • No acute or chronic liver related illness
  3. Signed informed consent/assent

Exclusion Criteria:

  1. Evidence of multi-organ system failure (e.g. combined liver and kidney failure)
  2. For subjects < 5 months old, treatment with antibiotics prior to enrollment into study

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: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Biliary atresia
Biliary atresia is an obstructive cholangiopathy of infancy. It is the most common cause of neonatal cholestasis and the most frequent indication for liver transplantation in children. Patients with biliary atresia have conjugated hyperbilirubinemia (serum direct bilirubin > 1mg/dL) AND are scheduled for/undergo exploratory laparotomy for diagnosis and Kasai portoenterostomy for surgical treatment of BA.
Non-BA=disease controls
All infants with other cholestatic syndromes (except biliary atresia) will be eligible for study enrollment in disease controls/non-biliary atresia. This involves the diagnosis of liver diseases caused by syndromes of intrahepatic cholestasis with or without hyperbilirubinemia.
Normal
All healthy infants with no acute or chronic liver related illness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in intestinal microbiome signature.
Time Frame: Through study completion, an average of 24 months.
Change in intestinal microbiome signature at the time of diagnosis of biliary atresia (up to 3 months of age/ at HPE) as compared with disease control and normal.
Through study completion, an average of 24 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiome signature and serum direct/ conjugated bilirubin.
Time Frame: Through study completion, an average of 24 months.
Correlation between the microbiome signature and normalization of serum direct/ conjugated bilirubin 3months after HPE.
Through study completion, an average of 24 months.
Microbiome signature and survival at 1 yr of age.
Time Frame: Through study completion, an average of 36 months.
Correlation between the microbiome signature and survival with the native liver at 1 yr of age.
Through study completion, an average of 36 months.
Microbiome signature and survival at 2 yr of age.
Time Frame: Through study completion, an average of 48 months.
Correlation between the microbiome signature and survival with the native liver at 2 yr of age.
Through study completion, an average of 48 months.
Microbiome signature and ascending cholangitis.
Time Frame: Through study completion, an average of 48 months.
Change in intestinal microbiome signature specific for ascending cholangitis up to and include 2 yr of age.
Through study completion, an average of 48 months.
Change in microbiome signature and liver transplant.
Time Frame: Through study completion, an average of 48 months.
Change in microbiome signature specific for end-stage liver disease (liver transplant) up to and include 2 yr of age..
Through study completion, an average of 48 months.

Collaborators and Investigators

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

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

Wuhan Union Hospital, China

Investigators

  • Principal Investigator: Jorge A Bezerra, MD, Professor of Pediatrics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Anticipated)

December 1, 2023

Primary Completion (Anticipated)

March 1, 2029

Study Completion (Anticipated)

March 1, 2032

Study Registration Dates

First Submitted

January 30, 2019

First Submitted That Met QC Criteria

March 24, 2019

First Posted (Actual)

March 26, 2019

Study Record Updates

Last Update Posted (Actual)

January 25, 2023

Last Update Submitted That Met QC Criteria

January 22, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIN001-Microbiome study in BA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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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