Back to resultsAn Efficacy Trial of Low Dose All-trans Retinoic Acid in Patients With Primary Sclerosing Cholangitis
Primary Purpose
Cholangitis, Sclerosing
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
All-trans retinoic acid
Sponsored by
About this trial
This is an interventional treatment trial for Cholangitis, Sclerosing
Eligibility 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.
Sites / Locations
- Yale University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All-trans retinoic acid (ATRA) therapy
Arm Description
Fixed low dose of ATRA 10 mg twice daily for 24 weeks.
Outcomes
Primary Outcome Measures
Change of Serum Alkaline Phosphatase (ALP)
Blood will be drawn at each time point to compare pre- and post-treatment values for each individual.
Secondary Outcome Measures
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.
The Percent of Patients Who Have Reduction of Serum C4 by 50%
Blood is drawn at each time point to assess the outcome.
The Percent of Patients Who Have Reduction of Serum Bile Acids by 50%
Blood is drawn at each time point to assess the outcome.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03359174
Brief Title
An Efficacy Trial of Low Dose All-trans Retinoic Acid in Patients With Primary Sclerosing Cholangitis
Official Title
An Efficacy Trial of Low Dose All-trans Retinoic Acid (ATRA) in Patients With Primary Sclerosing Cholangitis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
low recruitment
Study Start Date
May 29, 2018 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
January 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangitis, Sclerosing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All-trans retinoic acid (ATRA) therapy
Arm Type
Experimental
Arm Description
Fixed low dose of ATRA 10 mg twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
All-trans retinoic acid
Intervention Description
Fixed low dose of ATRA 10 mg twice daily for 24 weeks.
Primary Outcome Measure Information:
Title
Change of Serum Alkaline Phosphatase (ALP)
Description
Blood will be drawn at each time point to compare pre- and post-treatment values for each individual.
Time Frame
Baseline to week 24.
Secondary Outcome Measure Information:
Title
Change in Patients Who Have Normalization of Serum ALP or Reduction to Less Than 1.5 x Upper Limit of Normal (ULN)
Description
Blood is drawn at each time point to assess the outcome.
Time Frame
Baseline to week 24.
Title
The Percent of Patients Who Have Reduction of Serum C4 by 50%
Description
Blood is drawn at each time point to assess the outcome.
Time Frame
Baseline to week 24.
Title
The Percent of Patients Who Have Reduction of Serum Bile Acids by 50%
Description
Blood is drawn at each time point to assess the outcome.
Time Frame
Baseline to week 24.
Title
The Percent of Patients Who Have Reduction of Serum Alanine Aminotransferase (ALT) by 50%
Description
Blood is drawn at each time point to assess the outcome.
Time Frame
Baseline to week 24.
Title
The Percent of Patients Who Have Reduction of Serum Enhanced Liver Fibrosis Score (ELF) by 10%
Description
Blood is drawn at each time point to assess the outcome.
Time Frame
Baseline to week 24.
Title
The Percent of Patients Who Have Improvement in Fibrosis Per Transient Elastography by at Least 1 Stage
Description
Transient Elastography will be performed at baseline and week 24 to assess the outcome.
Time Frame
Baseline to week 24.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Boyer, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
12. IPD Sharing Statement
Learn more about this trial
An Efficacy Trial of Low Dose All-trans Retinoic Acid in Patients With Primary Sclerosing Cholangitis
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