Primary Sclerosing Cholangitis in Children

NCT04181138 | Recruiting DMC

• 2 other identifiers: PSC Study - ChiLDReN Network2U24DK062456
• Study Type: observational
• Target: 1,000
• Locations: 2 countries
• Sites: 12

Brief Summary

Primary sclerosing cholangitis (PSC) is a rare liver disease that damages the liver's bile ducts. Bile ducts are tiny tubes that carry bile from the liver to the small intestine. Bile is a liquid produced by the liver that helps us absorb and use the nutrients in the food we eat. In people with PSC, the bile backs up into the liver and will damage it, causing scarring of the liver. The purposes of this study are to:

• Collect medical and other data to learn more about PSC, how it progresses, and identify factors that may cause the disease to progress more quickly.
• Ask questions about how PSC symptoms affect your child's life to learn more about its impact on your child's daily functioning
• Children with PSC who are seen at one of the participating clinical sites in the Childhood Liver Disease Research Network (ChiLDReN) will be asked to contribute information, DNA, and other specimens. The information and specimens will be available to investigators to carry out approved research aimed at learning more about the possible causes and long-term effects of PSC.

Conditions

Primary Sclerosing Cholangitis; Liver Diseases; Cholangitis, Sclerosing

Keywords

Pediatric Liver Disease; Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (1)

• To characterize the major phenotypes of PSC including patients with large duct or small duct disease, with and without Inflammatory Bowel Disease (IBD), and with and without Auto Immune Hepatitis (AIH)

  Data will be collected on all phenotypes of PSC but attention is focused on how the intestinal inflammation and clinical activity of Inflammatory Bowel Disease (IBD) affect the progression of PSC, better classification of patients with features of Auto Immune Hepatitis (AIH), and the implications of bacterial cholangitis amongst all PSC phenotypes. Collection of retrospective clinical and laboratory data from the time of diagnosis of PSC and annual timepoints thereafter. Information regarding clinically important timepoints, laboratory data and FibroScan Liver Stiffness Measurements (LSM) are collected prospectively. Slides/images (if available) from each liver biopsy obtained at the time of diagnosis of PSC and thereafter and from the explanted liver recovered at the time of liver transplantation will undergo central review. Cholangiography results (MRCP, ERCP) will also undergo central review.

  up to 10 years

Secondary Outcomes (3)

• To identify the symptoms of PSC in children and the affects of those symptoms on the functional health of children.

  up to 10 years

• Utilizing imaging modalities measuring liver fibrosis, and large duct injury to correlate with other markers of fibrosis and biliary injury and predict progression of disease.

  up to 10 years

• Development of a repository for formalin fixed paraffin embedded (FFPE) liver biopsy tissue, serum, plasma, peripheral blood mononuclear cells (PBMCs), DNA and stool.

  up to 10 years

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants are eligible for enrollment into the ChiLDReN PSC Study if they meet the inclusion criteria and if none of the exclusion criteria apply. Every effort will be made to enroll as diverse a patient population (racial, ethnic, sex, age, etc) as possible.

You may qualify if:

• Patients with the clinical diagnosis of large or small duct PSC made at any time prior to enrollment are screened for eligibility to participate in this prospective cohort study. The site PI will determine eligibility following review of MRCP or ERCP images with the site radiologist to confirm presence of an abnormal cholangiogram at the time of diagnosis of large duct PSC. Liver histopathology obtained at the time of diagnosis of small duct PSC will be reviewed with the site pathologist prior to enrollment.
• Aged 2 through 25 years at time of screening.
• Diagnosis of large duct PSC based on review of cholangiogram by MRC, ERC, or intraoperative cholangiogram (IOC) by the site radiologist and interpreted to be consistent with PSC, based on one or more of the following:
• Focal structuring of the bile duct(s)
• Dominant stricture of the common bile duct
• Saccular dilatation of bile duct(s)
• Beaded appearance of bile duct(s)
• Pruning appearance of the distal bile duct branches
• AND/OR
• Diagnosis of small duct PSC based on review of liver histopathology by the site pathologist and interpreted to be compatible with PSC:
• Probable small duct PSC: biopsy with ≥3 of 5 criteria: periductal edema, concentric inflammation, bile duct injury, ductular reaction, and neutrophils in bile ducts (cholangitis) OR...
• Definitive small duct PSC: Periductal fibrosis/ "onion skinning" around interlobular bile ducts or smaller profiles
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Able to provide informed consent/assent
• Participants for the imaging study are eligible if they are:

You may not qualify if:

• An individual who meets any of the following criteria at baseline will be excluded from participation in this study.
• History of liver transplantation
• History bone marrow transplantation
• History of primary or acquired immunodeficiency predisposing to secondary sclerosing cholangitis, for instance: hyper-IgM syndrome, severe combined immunodeficiency (SCID) syndrome, common variable immunodeficiency (CVID) syndrome, cartilage hair hypoplasia syndrome, or HIV/AIDS
• History of histiocytosis, including Langerhans cell histiocytosis (LCH), or hemophagocytic lymphohistiocytosis (HLH)
• History of ischemic cholangitis
• History of portal vein thrombosis with biliopathy, veno-occlusive disease, or abdominal radiation vasculopathy
• History of recurrent pyogenic cholangitis
• History of biliary tract surgery for cholecystolithiasis prior to cholangiogram/liver biopsy evaluated to determine enrollment
• History of biliary tract surgery for choledochal cyst
• History of hepatocellular carcinoma, or hepatoblastoma
• History of surgical biliary trauma
• History of congenital cytomegalovirus (CMV) hepatitis
• History of Sickle Cell Disease
• History of cystic fibrosis, biliary atresia, Caroli disease/congenital hepatic fibrosis, or progressive familial intrahepatic cholestasis type 3/MDR3 disease

Sponsors & Collaborators

• Arbor Research Collaborative for Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (12)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Ann & Robert H Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

COMPLETED

Cincinnati Children's Hospital Medical

Cincinnati, Ohio, 45229, United States

RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, 77030, United States

RECRUITING

The University of Utah

Salt Lake City, Utah, 84113, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

COMPLETED

Related Publications (14)

• Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet. 2013 Nov 9;382(9904):1587-99. doi: 10.1016/S0140-6736(13)60096-3. Epub 2013 Jun 28.

  PMID: 23810223 BACKGROUND

• Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013 Sep;145(3):521-36. doi: 10.1053/j.gastro.2013.06.052. Epub 2013 Jul 1.

  PMID: 23827861 BACKGROUND

• Bambha K, Kim WR, Talwalkar J, Torgerson H, Benson JT, Therneau TM, Loftus EV Jr, Yawn BP, Dickson ER, Melton LJ 3rd. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003 Nov;125(5):1364-9. doi: 10.1016/j.gastro.2003.07.011.

  PMID: 14598252 BACKGROUND

• Deneau M, Jensen MK, Holmen J, Williams MS, Book LS, Guthery SL. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology. 2013 Oct;58(4):1392-400. doi: 10.1002/hep.26454. Epub 2013 Aug 13.

  PMID: 23686586 BACKGROUND

• Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol. 2011 Jul 18;11:83. doi: 10.1186/1471-230X-11-83.

  PMID: 21767410 BACKGROUND

• Olsson R, Danielsson A, Jarnerot G, Lindstrom E, Loof L, Rolny P, Ryden BO, Tysk C, Wallerstedt S. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. 1991 May;100(5 Pt 1):1319-23.

  PMID: 2013375 BACKGROUND

• Ricciuto A, Kamath BM, Griffiths AM. The IBD and PSC Phenotypes of PSC-IBD. Curr Gastroenterol Rep. 2018 Mar 28;20(4):16. doi: 10.1007/s11894-018-0620-2.

  PMID: 29594739 BACKGROUND

• Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, Fischler B, Gupte G, Hierro L, Indolfi G, Jahnel J, Smets F, Verkade HJ, Hadzic N. Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):345-360. doi: 10.1097/MPG.0000000000001801.

  PMID: 29356770 BACKGROUND

• Debray D, Pariente D, Urvoas E, Hadchouel M, Bernard O. Sclerosing cholangitis in children. J Pediatr. 1994 Jan;124(1):49-56. doi: 10.1016/s0022-3476(94)70253-5.

  PMID: 8283375 BACKGROUND

• Smolka V, Karaskova E, Tkachyk O, Aiglova K, Ehrmann J, Michalkova K, Konecny M, Volejnikova J. Long-term follow-up of children and adolescents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis. Hepatobiliary Pancreat Dis Int. 2016 Aug;15(4):412-8. doi: 10.1016/s1499-3872(16)60088-7.

  PMID: 27498582 BACKGROUND

• Feldstein AE, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003 Jul;38(1):210-7. doi: 10.1053/jhep.2003.50289.

  PMID: 12830004 BACKGROUND

• Miloh T, Arnon R, Shneider B, Suchy F, Kerkar N. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009 Feb;7(2):239-45. doi: 10.1016/j.cgh.2008.10.019. Epub 2008 Oct 30.

  PMID: 19121649 BACKGROUND

• Valentino PL, Wiggins S, Harney S, Raza R, Lee CK, Jonas MM. The Natural History of Primary Sclerosing Cholangitis in Children: A Large Single-Center Longitudinal Cohort Study. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):603-609. doi: 10.1097/MPG.0000000000001368.

  PMID: 27504812 BACKGROUND

• Wilschanski M, Chait P, Wade JA, Davis L, Corey M, St Louis P, Griffiths AM, Blendis LM, Moroz SP, Scully L, et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology. 1995 Nov;22(5):1415-22.

  PMID: 7590657 BACKGROUND

Related Links

• Childhood Liver Disease Research Network (ChiLDReN) website

Biospecimen

Retention: SAMPLES WITH DNA

DNA, plasma, serum, PBMCs, stool, liver tissue

MeSH Terms

Conditions

Cholangitis, Sclerosing; Liver Diseases

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Cara Mack, MD

  Medical College of Wisconsin-Milwaukee

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

• Katrina Loh, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

• John Magee, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Lisa Henn, PhD

  Arbor Research Collaborative for Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Terese A Howell, BS, CCRC

CONTACT

734-476-5340; terri.howell@arborresearch.org

Melissa Sexton, BBA, CCRP

CONTACT

734-693-3811; melissa.sexton@arborresearch.org

Study Design

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

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: November 29, 2019
• Study Start: December 30, 2021
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

US (11); CA (1)