Intestinal Microbiome Composition in Infants With Biliary Atresia (BA)

NCT ID: NCT03890536

Last Updated: 2025-07-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2023-12-31

Study Completion Date

2032-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Biliary Atresia Intrahepatic Cholestases Normal Controls

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

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.

No interventions assigned to this group

Normal

All healthy infants with no acute or chronic liver related illness.

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

1 Day

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jorge A Bezerra, MD

Role: PRINCIPAL_INVESTIGATOR

Professor of Pediatrics

Locations

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Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Countries

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United States

References

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Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, Sokol RJ. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology. 1996 Jun;23(6):1682-92. doi: 10.1002/hep.510230652.

Reference Type BACKGROUND
PMID: 8675193 (View on PubMed)

Bessho K, Bezerra JA. Biliary atresia: will blocking inflammation tame the disease? Annu Rev Med. 2011;62:171-85. doi: 10.1146/annurev-med-042909-093734.

Reference Type BACKGROUND
PMID: 21226614 (View on PubMed)

Mack CL, Feldman AG, Sokol RJ. Clues to the etiology of bile duct injury in biliary atresia. Semin Liver Dis. 2012 Nov;32(4):307-16. doi: 10.1055/s-0032-1329899. Epub 2013 Feb 8.

Reference Type BACKGROUND
PMID: 23397531 (View on PubMed)

Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013 Jul;58(1):120-7. doi: 10.1002/hep.26319. Epub 2013 May 14.

Reference Type BACKGROUND
PMID: 23401313 (View on PubMed)

Tabibian JH, Talwalkar JA, Lindor KD. Role of the microbiota and antibiotics in primary sclerosing cholangitis. Biomed Res Int. 2013;2013:389537. doi: 10.1155/2013/389537. Epub 2013 Oct 22.

Reference Type BACKGROUND
PMID: 24232746 (View on PubMed)

Kane M, Case LK, Kopaskie K, Kozlova A, MacDearmid C, Chervonsky AV, Golovkina TV. Successful transmission of a retrovirus depends on the commensal microbiota. Science. 2011 Oct 14;334(6053):245-9. doi: 10.1126/science.1210718.

Reference Type BACKGROUND
PMID: 21998394 (View on PubMed)

Kuss SK, Best GT, Etheredge CA, Pruijssers AJ, Frierson JM, Hooper LV, Dermody TS, Pfeiffer JK. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science. 2011 Oct 14;334(6053):249-52. doi: 10.1126/science.1211057.

Reference Type BACKGROUND
PMID: 21998395 (View on PubMed)

Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol. 2009 Dec;75(23):7537-41. doi: 10.1128/AEM.01541-09. Epub 2009 Oct 2.

Reference Type BACKGROUND
PMID: 19801464 (View on PubMed)

Other Identifiers

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CIN001-Microbiome study in BA

Identifier Type: -

Identifier Source: org_study_id

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