Clinical trial NCT03359174: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholangitis, Sclerosing
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2017-12-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change of Serum Alkaline Phosphatase (ALP)
timeFrame: Baseline to week 24.
Secondary outcomes:
measure: Change in Patients Who Have Normalization of Serum ALP or Reduction to Less Than 1.5 x Upper Limit of Normal (ULN)
timeFrame: Baseline to week 24.
measure: The Percent of Patients Who Have Reduction of Serum C4 by 50%
timeFrame: Baseline to week 24.
measure: The Percent of Patients Who Have Reduction of Serum Bile Acids by 50%
timeFrame: Baseline to week 24.
measure: The Percent of Patients Who Have Reduction of Serum Alanine Aminotransferase (ALT) by 50%
timeFrame: Baseline to week 24.
measure: The Percent of Patients Who Have Reduction of Serum Enhanced Liver Fibrosis Score (ELF) by 10%
timeFrame: Baseline to week 24.
measure: The Percent of Patients Who Have Improvement in Fibrosis Per Transient Elastography by at Least 1 Stage
timeFrame: Baseline to week 24.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: James Boyer, MD
role: PRINCIPAL_INVESTIGATOR
References: