Clinical trial NCT00345553: Biliary Atresia Study in Infants and Children
Official title: Biliary Atresia Study in Infants and Children (BASIC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Atresia
Keywords: Biliary Atresia
Cholestasis
Lead sponsor: Arbor Research Collaborative for Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2006-06-28
Enrollment: 1265
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recruitment will be open to any eligible subject. The method of contacting the study subjects will conform to local IRB guidelines, but in general: the parents or guardians of all eligible subjects at each ChiLDReN center, or the subjects themselves if 18 years of age or older, will be approached to participate. New patients who are not participating in ChiLDReN study PROBE may be approached for study participation, but will not be eligible for enrollment until 6 months of age.

Brief summary: Little is known about the factors that cause biliary atresia nor the factors that influence disease progression. The purpose of this study is to collect the pertinent clinical information, genetic material and body fluid samples to enable investigators to address the following aims: To identify the gene or genes implicated in the etiology of BA; To identify polymorphisms that may be important in disease progression such as HLA polymorphisms; To characterize the natural history of the older, non-transplanted child with BA.

Detailed description: Little is known about the factors that cause biliary atresia nor the factors that influence disease progression. A variety of genetic, autoimmune and environmental influences have been hypothesized to be important. Most studies to date have focused on the neonate and young child with BA, yet the older surviving child with BA can provide important information about genetics, as well as, natural history.

The purpose of this study is to collect the pertinent clinical information, genetic material and body fluid samples to enable investigators to address the following hypotheses:

Hypothesis 1: A genetic defect is a likely causative factor for BA among children with BA and multiple congenital anomalies.

Hypothesis 2: Autoimmune factors are likely to contribute to disease progression or acquisition and can be identified by correlating HLA among children with BA to healthy controls and by comparison of those who develop early complications including, variceal bleed, ascites, and growth failure compared to those who do not.

Hypothesis 3a: Sentinel events such as variceal bleeding, ascites and growth failure are earlier predictors of death or need for liver transplantation than the pediatric end-stage liver disease score (PELD).

Hypothesis 3b: Health related quality of life will be impaired compared to healthy age matched children and relate to severity of illness.

Hypothesis 3c: Growth failure as measured by anthropometrics and nutritional supplementation will be predictive of onset of sentinel events (ascites, variceal bleed, death, and transplant) in the following 24 months.

This study will be performed by the Childhood Liver Disease Research Network (ChiLDReN), a National Institute of Diabetes \& Digestive and Kidney Diseases (NIDDK) funded network.

Eligibility criteria: Inclusion Criteria:

1. Participants need to have a confirmed diagnosis of BA determined by chart review including review of pertinent diagnostic biopsy reports, radiologic reports and surgical reports (if surgery was performed).
2. Participants need to be \>6 months of age up to and equal to the age of 20 (participants enrolled at 20 years of age will have one visit).
3. Participants either have their native liver or have a confirmed liver transplantation.
4. Parent, guardian or participant (if 18 years of age or older) is willing to provide informed consent and, when appropriate, the participant is willing to assent.

Exclusion Criteria:

1. Currently participating in the ChiLDReN study PROBE
2. Inability to confirm original diagnostic evaluation of biliary atresia
3. Inability or unwillingness of family or participant to participate in all scheduled visits.

Primary outcomes:
measure: To identify the gene or genes implicated in the etiology of BA
timeFrame: Specimens for this aim are collected once during study, usually at baseline.
Secondary outcomes:
measure: To identify polymorphisms that may be important in disease progression such as Human leukocyte antigen (HLA) polymorphisms
timeFrame: Specimens for this aim are collected once during study, usually at baseline.
measure: Define the natural history of the older, non-transplanted child with biliary atresia
timeFrame: Observational information collected at entrance into study as well as at each yearly follow-up visit.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: St Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital (Baylor College of Medicine)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto, ON, Canada
name: Vicky Ng, MD
role: STUDY_CHAIR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Ed Doo, MD
role: STUDY_DIRECTOR
affiliation: University of Michigan
name: John C Magee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arbor Research Collaborative for Health - Data Coordinating Center
name: Lisa Henn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Averell Sherker, MD
role: STUDY_DIRECTOR
References:
citation: Ng VL, Haber BH, Magee JC, Miethke A, Murray KF, Michail S, Karpen SJ, Kerkar N, Molleston JP, Romero R, Rosenthal P, Schwarz KB, Shneider BL, Turmelle YP, Alonso EM, Sherker AH, Sokol RJ; Childhood Liver Disease Research and Education Network (CHiLDREN). Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr. 2014 Sep;165(3):539-546.e2. doi: 10.1016/j.jpeds.2014.05.038. Epub 2014 Jul 9.