Safety and Efficacy Study of Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis

Summary

Primary sclerosing cholangitis (PSC), although uncommon, is a devastating and insidiously progressive liver disease, resulting from advancing inflammation, fibrosis and obliteration of the bile ducts in the liver, leading to cirrhosis and end-stage liver disease. Although prognosis in children may be somewhat better than that of adults, approximately one third of pediatric patients require transplantation by adulthood. Other than transplantation, there is to date no therapy conclusively proven to improve the long-term outcome. Ursodeoxycholic acid (UDCA) improves biochemical markers of liver disease, although in high doses does not clearly improve the long-term outcome in adults, and in a recent study may have actually worsened outcome. Childhood PSC is different from that of adult PSC in many ways, and children may derive more short-term, as well as long-term, benefit than adults. This unique multicenter study will carefully monitor the effects of withdrawal and restarting UDCA on liver injury and inflammation in children with PSC. The preliminary data will help in the design of a more definitive larger study to determine if UDCA has a beneficial role in the treatment of PSC in children. Funding Source - FDA OOPD

Conditions

• Primary Sclerosing Cholangitis

Interventions

DRUG

ursodeoxycholic acid (UDCA)

Pediatric PSC patients already receiving UDCA therapy will enter a four-phase trial consisting of baseline data collection (phase I, 4 weeks), 50% reduction in UDCA dose (phase II, 4 weeks), discontinuation of UDCA (phase III, 8 weeks) and reinstitution of therapy at a dose of 20 mg/kg/day (phase IV, 8 weeks). Surveillance and endpoint evaluation for each phase will include liver chemistries and clinical data. Comparisons will be made between baseline and the end of phase III (primary outcome) and between the end of phase III and the end of phase IV (secondary outcome). Serum cytokine biomarkers will be measured and compared between baseline and the end of phase III and between the end of phases III and IV.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai

  collaborator OTHER

• Ann & Robert H Lurie Children's Hospital of Chicago

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• University of California, San Francisco

  collaborator OTHER

• University of Pittsburgh

  collaborator OTHER

• Phoenix Children's Hospital

  collaborator OTHER

• Children's Hospital of Philadelphia

  collaborator OTHER

• Children's Healthcare of Atlanta

  collaborator OTHER

• Children's Hospital Los Angeles

  collaborator OTHER

• Baylor College of Medicine

  collaborator OTHER

• Yale University

  collaborator OTHER

• University of Tennessee

  lead OTHER

Principal Investigators

• Dennis D Black, M.D. · University of Tennessee

• Benjamin Shneider, M.D. · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

5 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-10-31

Primary Completion

2016-12-31

Completion

2017-06-30

Countries

• United States

Study Locations