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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cholangitis, Sclerosing
• Intervention / Treatment: Drug: All-trans retinoic acid

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: James Boyer, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: November 27, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: 2000021447

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No