Biliary AtresiaBANCT03890536
Intestinal Microbiome Composition in Infants With Biliary Atresia (BA)
An observational study of Biliary Atresia and Intrahepatic Cholestases, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 2 yearsHealthy volunteers can take part
- Conditions the study is for
- Biliary Atresia, Intrahepatic Cholestases, Normal Controls
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2023to Mar 2032
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 2 years
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- Age:
- -Birth to 5 months
- Disease state: Must meet either (a), (b), or (c) for eligibility.
- 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
- Neonatal cholestasis secondary to other causes of liver disease:
Show all 10Show fewer
- Diagnosis of liver disease caused by syndromes of intrahepatic cholestasis with or without hyperbilirubinemia
- Normal controls:
- No acute or chronic liver related illness
- Signed informed consent/assent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: 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.
Read the 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.
- Conditions
- Biliary Atresia, Intrahepatic Cholestases, Normal Controls
- Keywords
- Microbiome
- Medical subject headings
- Biliary Atresia, Cholestasis, Intrahepatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 24 months.
Secondary outcomes (5)
Microbiome signature and serum direct/ conjugated bilirubin.
Correlation between the microbiome signature and normalization of serum direct/ conjugated bilirubin 3months after HPE.
Measured: Through study completion, an average of 24 months.
Microbiome signature and survival at 1 yr of age.
Correlation between the microbiome signature and survival with the native liver at 1 yr of age.
Measured: Through study completion, an average of 36 months.
Microbiome signature and survival at 2 yr of age.
Correlation between the microbiome signature and survival with the native liver at 2 yr of age.
Measured: Through study completion, an average of 48 months.
Microbiome signature and ascending cholangitis.
Change in intestinal microbiome signature specific for ascending cholangitis up to and include 2 yr of age.
Measured: Through study completion, an average of 48 months.
Change in microbiome signature and liver transplant.
Change in microbiome signature specific for end-stage liver disease (liver transplant) up to and include 2 yr of age..
Measured: Through study completion, an average of 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2019
- Study startDec 2023 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionMar 2032 (estimated)
Why it stopped: Study never began enrolling. Study team left institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Biliary AtresiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jorge A Bezerra, MD, Principal investigator, Professor of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03890536
- Sponsor's protocol ID
- CIN001-Microbiome study in BA
- Acronym
- BA
- Status last verified
- Jul 2025
- First submitted
- 30 Jan 2019
- Last updated
- 9 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 8675193Bessho 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.
PubMed 21226614Mack 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.
PubMed 23397531Mouzaki 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.
PubMed 23401313Tabibian 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.
PubMed 24232746Kane 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.
PubMed 21998394Kuss 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.
PubMed 21998395Schloss 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.
PubMed 19801464
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intestinal Microbiome Composition in Infants With Biliary Atresia
- ClinicalTrials.gov ID
- NCT03890536
- Acronym / sponsor ID
- BA / CIN001-Microbiome study in BA
- Conditions
- Biliary Atresia, Intrahepatic Cholestases, Normal Controls
- Keywords
- Microbiome
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study never began enrolling. Study team left institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Study start
- Dec 2023 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2032 (estimated)
- First posted
- 26 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 1 day to 2 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (10 listed)
- Age:
- -Birth to 5 months
- Disease state: Must meet either (a), (b), or (c) for eligibility.
- Signed informed consent/assent
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
5 secondary outcomes
Microbiome signature and serum direct/ conjugated bilirubin.
Time frame: 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.
Microbiome signature and survival at 2 yr of age.
Time frame: 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 microbiome signature and liver transplant.
Time frame: Through study completion, an average of 48 months.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Background: PubMed 8675193Balistreri 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.
- Background: PubMed 21226614Bessho 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.
- Background: PubMed 23397531Mack 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.
- Background: PubMed 23401313Mouzaki 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.
- Background: PubMed 24232746Tabibian 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.
- Background: PubMed 21998394Kane 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.
- Background: PubMed 21998395Kuss 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.
- Background: PubMed 19801464Schloss 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge A Bezerra, MD principal investigator
Professor of Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Biliary Atresia and Intrahepatic Cholestases, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in intestinal microbiome signature. (time frame: Through study completion, an average of 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03890536, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.