Intestinal Microbiome Composition in Infants With Biliary Atresia (BA)

NCT03890536 | Withdrawn

• 1 other identifier: CIN001-Microbiome study in BA
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Atresia; Intrahepatic Cholestases; Normal Controls

Keywords

Microbiome

Outcome Measures

Primary Outcomes (1)

• Change in intestinal microbiome signature.

  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 Outcomes (5)

• Microbiome signature and serum direct/ conjugated bilirubin.

  Through study completion, an average of 24 months.

• Microbiome signature and survival at 1 yr of age.

  Through study completion, an average of 36 months.

• Microbiome signature and survival at 2 yr of age.

  Through study completion, an average of 48 months.

• Microbiome signature and ascending cholangitis.

  Through study completion, an average of 48 months.

• Change in microbiome signature and liver transplant.

  Through study completion, an average of 48 months.

Study Arms (3)

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.

Eligibility Criteria

• Age: 1 Day - 2 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• Age:
• Birth to 5 months
• 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
• Signed informed consent/assent

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (8)

• 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.

  PMID: 8675193 BACKGROUND

• 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.

  PMID: 21226614 BACKGROUND

• 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.

  PMID: 23397531 BACKGROUND

• 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.

  PMID: 23401313 BACKGROUND

• 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.

  PMID: 24232746 BACKGROUND

• 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.

  PMID: 21998394 BACKGROUND

• 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.

  PMID: 21998395 BACKGROUND

• 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.

  PMID: 19801464 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Stool specimens will be collected from infants with Biliary atresia, non-biliary atresia liver disease and control subjects with no disease. Bacterial genomic DNA will be isolated from stool samples of the above-mentioned subjects.

MeSH Terms

Conditions

Biliary Atresia; Cholestasis, Intrahepatic

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cholestasis; Liver Diseases

Study Officials

• Jorge A Bezerra, MD

  Professor of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: March 26, 2019
• Study Start: December 1, 2023
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2032
• Last Updated: July 9, 2025

Record last verified: 2025-07

Locations

US (1)