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

• ClinicalTrials.gov Identifier: NCT03359174
• Recruitment Status: Terminated
• First Posted: December 2, 2017
• Results First Posted: August 9, 2021
• Last Update Posted: August 9, 2021
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cholangitis, Sclerosing	Drug: All-trans retinoic acid	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Efficacy Trial of Low Dose All-trans Retinoic Acid (ATRA) in Patients With Primary Sclerosing Cholangitis
• Actual Study Start Date: May 29, 2018
• Actual Primary Completion Date: December 1, 2020
• Actual Study Completion Date: January 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: All-trans retinoic acid (ATRA) therapy; Fixed low dose of ATRA 10 mg twice daily for 24 weeks.	Drug: All-trans retinoic acid; Fixed low dose of ATRA 10 mg twice daily for 24 weeks.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06510

Sponsors and Collaborators

Yale University

Investigators

• Principal Investigator: James Boyer, MD; Yale University

  Study Documents (Full-Text)

Documents provided by Yale University:

Study Protocol and Statistical Analysis Plan  [PDF] September 17, 2018

More Information

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT03359174
• Other Study ID Numbers: 2000021447
• First Posted: December 2, 2017
• Results First Posted: August 9, 2021
• Last Update Posted: August 9, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cholangitis; Cholangitis, Sclerosing; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Tretinoin; Antineoplastic Agents; Keratolytic Agents; Dermatologic Agents