Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research study is to determine whether the combination of UDCA and ATRA taken for 3 months will improve laboratory tests of liver and bile duct inflammation in patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that a combination of these medications will improve the liver inflammatory tests in these patients, specifically a reduction in alkaline phosphatase (AP) by at least 30%.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Collaborator: Mayo Clinic
• Treatments: Tretinoin; Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

• Diagnosis of PSC for at least 6 months, made by clinical evaluation in addition to one of the following: a prior endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC, also termed MRI/MRCP) or liver biopsy.

• Progressing disease or stable disease with persistent elevation in AP despite treatment with UDCA (15 mg/kg/day) for at least 6 months.

• Measures of progressing disease:

1. Cholangitis within the past 12 months.

2. Presence or progression of biliary abnormalities on MRI/MRC.

3. Elevated liver tests (alkaline phosphatase, bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]).

• Age between 18 and 80.

Exclusion Criteria:

• Pregnancy or planned pregnancy during study period and within 6 months of study completion.

• Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher cardiac disease, hyperlipidemia, hypertriglyceridemia, hepatic injury, or adverse event related to administration of UDCA or ATRA.

• Prior intolerance to UDCA or ATRA (or related oral vitamin A compounds).

• Evidence of decompensated cirrhosis within the past 6 months (i.e. variceal bleeding, uncontrolled ascites, hepatic encephalopathy, jaundice).

• Estimated need for liver transplantation within 1 year.

• Any evidence of hepatocellular carcinoma, cholangiocarcinoma, or other malignancy.