Clinical trial NCT00061828: A Prospective Database of Infants With Cholestasis
Official title: Childhood Liver Disease Research Network (ChiLDReN): A Prospective Database of Infants With Cholestasis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Atresia
Neonatal 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: 2003-06-06
Enrollment: 1000
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study population will be selected from the patient base of participating specialty care clinics.

Brief summary: Biliary atresia, idiopathic neonatal hepatitis, and specific genetic cholestatic conditions are the most common causes of jaundice and hyperbilirubinemia that continue beyond the newborn period. The long term goal of the Childhood Liver Disease Research Network (ChiLDReN) is to establish a database of clinical information and plasma, serum, and tissue samples from cholestatic children to facilitate research and to perform clinical, epidemiological and therapeutic trials in these important pediatric liver diseases.

Detailed description: This is a multi-center project to establish a prospective database of clinical information and a repository of blood, and tissue samples from children with diagnoses of neonatal liver diseases, such as biliary atresia (BA), idiopathic neonatal hepatitis (INH), and specific neonatal presentations of genetic cholestatic disorders in order to perform research in these important liver problems. Children will be screened and enrolled at presentation at the participating pediatric liver sites. Participants diagnosed with BA will be followed intensively for the first year, at 18 months of age, and then annually up to 20 years of age, or liver transplantation. Other participants diagnosed with cholestasis will be followed on the same schedule; if there is complete (clinical and biochemical) resolution of their underlying liver disease off all therapy, there will be one follow up visit within one year (preferably scheduled at the time of the next planned follow up visit or at 12 months of age, whichever is later) for data collection and to obtain blood samples. The development of a serum and tissue bank of specimens from children with various neonatal cholestatic disorders will be an invaluable tool for current and future investigations into the etiology and pathogenesis of hepatobiliary injury in the infant.

Detailed clinical data, laboratory investigations, liver and biliary specimens, and long-term follow-up of outcomes are part of the normal standard of care with respect to the diagnosis and treatment of the subjects with liver problems. This research involves the collection of diagnostic, clinical and outcome data concerning the subject, which is kept without identification (coded) in a national research database of infants with liver disease. Samples of blood will be obtained for later research analysis, whenever possible, at the time of clinically indicated blood draws or when there is IV access for a clinical procedure. When liver biopsy specimens are obtained for diagnostic purposes, any liver biopsy specimen in excess of that needed for diagnostic use will be sent to the tissue repository. When a portoenterostomy or liver transplant occurs, sections of the liver and, biliary remnant removed in the course of surgery and in excess of that needed for diagnostic use, will be sent for the repository. These specimens will be used in investigations into the mechanisms and causes of the liver damage that occur in the participant's condition. . All data from this study will be kept in a secure research database at the Scientific Data Coordinating Center (SDCC) and transferred to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) data repository after the study ends.

Eligibility criteria: INCLUSION CRITERIA

* Infant's age less than or equal to 180 days at initial presentation at the ChiLDREN clinical site.
* Diagnosis of cholestasis defined by serum direct or conjugated bilirubin greater than 20% of total and greater than or equal to 2 mg/dl.
* The subject's parent(s)/guardian(s) willing to provide informed written consent.

EXCLUSION CRITERIA

* Acute liver failure.
* Previous hepatobiliary surgery with dissection or excision of biliary tissue.
* Diagnoses of bacterial or fungal sepsis (except where associated with metabolic liver disease)
* Diagnoses of hypoxia, shock or ischemic hepatopathy within the past two weeks (If the cholestasis persists beyond two weeks of the initiating event, the infant can be enrolled).
* Diagnosis of any malignancy.
* Presence of any primary hemolytic disease (except when diagnosed with biliary atresia or another cholestatic disease being studied by ChiLDREN).
* Diagnosis of any drug or Total parenteral nutrition (TPN)-associated cholestasis (except when diagnosed with biliary atresia or another cholestatic disease being studied by ChiLDREN).
* Diagnosis with Extracorporeal membrane oxygenation (ECMO)-associated cholestasis.
* Birth weight less than 1500g (except when diagnosed with biliary atresia).

Primary outcomes:
measure: Change in disease severity over time (disease progression)
timeFrame: Measured at baseline, 1month, 2 months, 3, 6 months post-baseline, 12 and 18 months of age, then annually through year 15.
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California
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 Hospital for Children
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 City
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati 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: 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: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Healthcare of Atlanta - Emory University
name: Saul Karpen, MD, PhD
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 Medical Center, Ann Arbor
name: John Magee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arbor Research Collaborative of Health
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: Hertel PM, Hawthorne K, Kim S, Finegold MJ, Shneider BL, Squires JE, Gupta NA, Bull LN, Murray KF, Kerkar N, Ng VL, Molleston JP, Bezerra JA, Loomes KM, Taylor SA, Schwarz KB, Turmelle YP, Rosenthal P, Magee JC, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study. J Pediatr Gastroenterol Nutr. 2021 Oct 1;73(4):478-484. doi: 10.1097/MPG.0000000000003248.
citation: Ng VL, Sorensen LG, Alonso EM, Fredericks EM, Ye W, Moore J, Karpen SJ, Shneider BL, Molleston JP, Bezerra JA, Murray KF, Loomes KM, Rosenthal P, Squires RH, Wang K, Arnon R, Schwarz KB, Turmelle YP, Haber BH, Sherker AH, Magee JC, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study. J Pediatr. 2018 May;196:139-147.e3. doi: 10.1016/j.jpeds.2017.12.048. Epub 2018 Mar 5.
citation: Shneider BL, Magee JC, Karpen SJ, Rand EB, Narkewicz MR, Bass LM, Schwarz K, Whitington PF, Bezerra JA, Kerkar N, Haber B, Rosenthal P, Turmelle YP, Molleston JP, Murray KF, Ng VL, Wang KS, Romero R, Squires RH, Arnon R, Sherker AH, Moore J, Ye W, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr. 2016 Mar;170:211-7.e1-2. doi: 10.1016/j.jpeds.2015.11.058. Epub 2015 Dec 24.
citation: Ye W, Rosenthal P, Magee JC, Whitington PF; Childhood Liver Disease Research and Education Network. Factors Determining delta-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr. 2015 May;60(5):659-63. doi: 10.1097/MPG.0000000000000690.
citation: Bessho K, Mourya R, Shivakumar P, Walters S, Magee JC, Rao M, Jegga AG, Bezerra JA. Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease. Hepatology. 2014 Jul;60(1):211-23. doi: 10.1002/hep.27045. Epub 2014 May 27.
citation: Shneider BL, Abel B, Haber B, Karpen SJ, Magee JC, Romero R, Schwarz K, Bass LM, Kerkar N, Miethke AG, Rosenthal P, Turmelle Y, Robuck PR, Sokol RJ; Childhood Liver Disease Research and Education Network. Portal hypertension in children and young adults with biliary atresia. J Pediatr Gastroenterol Nutr. 2012 Nov;55(5):567-73. doi: 10.1097/MPG.0b013e31826eb0cf.
citation: Zahm AM, Hand NJ, Boateng LA, Friedman JR. Circulating microRNA is a biomarker of biliary atresia. J Pediatr Gastroenterol Nutr. 2012 Oct;55(4):366-9. doi: 10.1097/MPG.0b013e318264e648.