Intestinal Microbiome Composition in Infants With Biliary Atresia (BA) (BA)
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|ClinicalTrials.gov Identifier: NCT03890536|
Recruitment Status : Not yet recruiting
First Posted : March 26, 2019
Last Update Posted : December 14, 2021
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.
|Condition or disease|
|Biliary Atresia Intrahepatic Cholestases Normal Controls|
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|
|Estimated Enrollment :||50 participants|
|Official Title:||Intestinal Microbiome Composition in Infants With Biliary Atresia|
|Estimated Study Start Date :||June 2022|
|Estimated Primary Completion Date :||March 2029|
|Estimated Study Completion Date :||March 2032|
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.
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.
All healthy infants with no acute or chronic liver related illness.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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..
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03890536
|Contact: Jorge A Bezerra, MDfirstname.lastname@example.org|
|Contact: Reena R Mourya, MScemail@example.com|
|Principal Investigator:||Jorge A Bezerra, MD||Professor of Pediatrics|