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

NCT03359174 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2000021447
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Cholangitis, Sclerosing

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in Patients Who Have Normalization of Serum ALP or Reduction to Less Than 1.5 x Upper Limit of Normal (ULN)

  Baseline to week 24.

• The Percent of Patients Who Have Reduction of Serum C4 by 50%

  Baseline to week 24.

• The Percent of Patients Who Have Reduction of Serum Bile Acids by 50%

  Baseline to week 24.

• The Percent of Patients Who Have Reduction of Serum Alanine Aminotransferase (ALT) by 50%

  Baseline to week 24.

• The Percent of Patients Who Have Reduction of Serum Enhanced Liver Fibrosis Score (ELF) by 10%

  Baseline to week 24.

Study Arms (1)

All-trans retinoic acid (ATRA) therapy

EXPERIMENTAL

Fixed low dose of ATRA 10 mg twice daily for 24 weeks.

Drug: All-trans retinoic acid

Interventions

All-trans retinoic acid DRUG

Fixed low dose of ATRA 10 mg twice daily for 24 weeks.

All-trans retinoic acid (ATRA) therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

Tretinoin

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Clinical Research Coordinator
• Organization: Yale Univeristy

laura.cusack@yale.edu

203 737 6839

Study Officials

• James Boyer, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 2, 2017
• Study Start: May 29, 2018
• Primary Completion: December 1, 2020
• Study Completion: January 1, 2021
• Last Updated: August 9, 2021
• Results First Posted: August 9, 2021

Record last verified: 2021-08

Locations

US (1)