An Efficacy Trial of Low Dose All-trans Retinoic Acid in Patients With Primary Sclerosing Cholangitis

Study Overview
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Brief Summary
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The purpose of this research study is to determine whether a low dose of ATRA will improve laboratory tests of liver and bile duct inflammation in patients with PSC. The investigators will also look for changes to other blood tests which are related to inflammation, scarring, and the immune system.

Official Title
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An Efficacy Trial of Low Dose All-trans Retinoic Acid (ATRA) in Patients With Primary Sclerosing Cholangitis

Conditions
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Cholangitis, Sclerosing

Intervention / Treatment
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* Drug: All-trans retinoic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ages 18-80 Diagnosis of large-duct PSC based on ERCP or MRCP, or liver biopsy findings without alternative explanation for findings, for at least 6 months. Serum ALP levels persistently more than 1.5 x upper limit of normal over the past 6 months. Ursodeoxycholic acid therapy must be discontinued for at least 3 months. At least 2 forms of barrier protection for males and females of child-bearing age. Exclusion Criteria: Small duct PSC, overlap with autoimmune hepatitis, IgG4 disease or secondary sclerosing cholangitis. Any malignancy, presently or within the past 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix or in situ prostate cancer. Viral hepatitis including hepatitis A, B, C, D, E. Decompensated cirrhosis, or planned liver transplantation. Recent diagnostic or therapeutic biliary manipulation (endoscopic, radiologic) within the past 3 months. Ascending Cholangitis requiring antibiotics within the past 3 months. Uncontrolled IBD, or IBD requiring the use of steroids. Acute or Chronic Kidney Disease with serum creatinine > 2 mg/dL. Allergy to ATRA or vitamin A compounds.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All-trans retinoic acid (ATRA) therapy<br>Fixed low dose of ATRA 10 mg twice daily for 24 weeks. | Drug: All-trans retinoic acid<br>* Fixed low dose of ATRA 10 mg twice daily for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Alkaline Phosphatase (ALP) | Blood will be drawn at each time point to compare pre- and post-treatment values for each individual. | Baseline to week 24. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patients Who Have Normalization of Serum ALP or Reduction to Less Than 1.5 x Upper Limit of Normal (ULN) | Blood is drawn at each time point to assess the outcome. | Baseline to week 24. | 
| The Percent of Patients Who Have Reduction of Serum C4 by 50% | Blood is drawn at each time point to assess the outcome. | Baseline to week 24. | 
| The Percent of Patients Who Have Reduction of Serum Bile Acids by 50% | Blood is drawn at each time point to assess the outcome. | Baseline to week 24. | 
| The Percent of Patients Who Have Reduction of Serum Alanine Aminotransferase (ALT) by 50% | Blood is drawn at each time point to assess the outcome. | Baseline to week 24. | 
| The Percent of Patients Who Have Reduction of Serum Enhanced Liver Fibrosis Score (ELF) by 10% | Blood is drawn at each time point to assess the outcome. | Baseline to week 24. | 
| The Percent of Patients Who Have Improvement in Fibrosis Per Transient Elastography by at Least 1 Stage | Transient Elastography will be performed at baseline and week 24 to assess the outcome. | Baseline to week 24. |