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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01088607
• Date of registration: 12/03/2010
• Prospective Registration: Yes
• Primary sponsor: University of Tennessee
• Public title: Safety and Efficacy Study of Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis
• Scientific title: Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: A Pilot Withdrawal/Reinstitution Trial
• Date of first enrolment: October 2010
• Target sample size: 27
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01088607
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada, United States

Contacts

• Name: Benjamin Shneider, M.D.
• Affiliation: Baylor College of Medicine

• Name: Dennis D Black, M.D.
• Affiliation: University of Tennessee Health Science Center

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female < 21 years of age, no racial or ethnic restrictions

2. Pediatric PSC diagnosed as per the criteria developed by STOPSC (2 of 3 required):

- Serum GGT increased more than 50% above the upper limit of normal for age

- Endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic
cholangiography (PTC) or magnetic resonance cholangiopancreatography (MRCP)
findings of intrahepatic and/or extrahepatic bile duct irregularities consistent
with PSC

- Liver biopsy abnormalities consistent with chronic biliary injury Note that these
criteria will include patients with small duct PSC who have normal biliary
imaging with the required biochemical and histologic criteria.

3. Patients with PSC/AIH overlap will also be included who meet the criteria for PSC plus
have liver histologic features of AIH.

4. Biochemically quiescent liver disease defined by an ALT and GGT < 2.0 X upper limit of
normal (ULN) measured on two separate occasions > 2 weeks apart

5. Prior and on-going UDCA therapy at a dose of at least 13 mg/kg/day or 600 mg/day for
more than 6 months

6. Ability to swallow pills

7. Quiescent inflammatory bowel disease (IBD) as reflected by a modified Pediatric
Ulcerative Colitis Activity Index score of less than 6 or a modified Pediatric Crohn's
Disease Activity Index score of less than 15.

8. Not excluded by the STOPSC pediatric PSC exclusion criteria (see Appendix) that are
designed to minimize misdiagnosis due to other primary liver diseases, previous
biliary injury/surgery, therapies, or systemic disorders that may secondarily affect
the liver and/or biliary tract.

9. Subjects will remain on all current medications, including those for IBD and
immunosuppressive therapy.

10. Female subjects of childbearing age will be required to have a pregnancy test, and if
sexually active, will be required to use an accepted method of birth control during
the course of the study.

11. Parent or legal guardian must be willing to provide signed and dated informed consent
documentation. Assent from the child or adolescent will be obtained as appropriate.

Exclusion Criteria:

1. Evidence of decompensated cirrhosis:

- Cirrhosis as defined by biopsy findings or evidence of portal hypertension with
no other known cause and:

- Platelet count < 100,000 or,

- Spleen palpable more than 2 cm below the left costal margin or,

- Ascites or,

- Varices or other GI manifestation of portal hypertension

- Decompensated liver disease defined by:

- Serum total bilirubin (TB) > 5 mg/dl and direct bilirubin (DB) > 1 mg/dl or,

- Prothrombin time (PT) prolonged by more than 3 seconds after parenteral
vitamin K administration or,

- Ascites requiring diuretic therapy or,

- Serum albumin < 3 g/dl

2. Evidence of acute liver failure:

- No prior history of liver disease and

- PT > 20 seconds or INR > 2.0 unresponsive to parenteral vitamin K administration
or,

- PT > 15 seconds or international normalized ratio (INR) > 1.5 with change in
mental status ascribable to hepatic encephalopathy

3. History of cholangitis or bile duct strictures requiring intervention

4. Liver transplantation



Age minimum: 5 Years
Age maximum: 21 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Sclerosing Cholangitis

Intervention(s)

Drug: ursodeoxycholic acid (UDCA)

Primary Outcome(s)

The primary outcome will be the change in alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) or biomarkers for inflammation in study subjects at baseline compared to the end of Phase III (UDCA discontinuation) of the study. [Time Frame: 16 weeks]

Secondary Outcome(s)

A secondary outcome will be the change in ALT, GGT or biomarkers for inflammation in study subjects at the end of Phase III (UDCA discontinuation) compared to the end of Phase IV (UDCA reinstitution) of the study. [Time Frame: 8 weeks]

Secondary ID(s)

FD-003709

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Children's Hospital of Philadelphia

Phoenix Children's Hospital

Texas Children's Hospital

Ann & Robert H Lurie Children's Hospital of Chicago

University of Colorado, Denver

Yale University

Children's Hospital Los Angeles

Icahn School of Medicine at Mount Sinai

University of Pittsburgh

Children's Healthcare of Atlanta

University of California, San Francisco