Cholangitis, Sclerosing
Conditions
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.
Interventions
DRUGAll-trans retinoic acid
Fixed low dose of ATRA 10 mg twice daily for 24 weeks.
Sponsors
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Serum Alkaline Phosphatase (ALP) | Baseline to week 24. | Blood will be drawn at each time point to compare pre- and post-treatment values for each individual. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percent of Patients Who Have Reduction of Serum C4 by 50% | Baseline to week 24. | Blood is drawn at each time point to assess the outcome. |
| The Percent of Patients Who Have Reduction of Serum Bile Acids by 50% | Baseline to week 24. | Blood is drawn at each time point to assess the outcome. |
| 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. | 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% | Baseline to week 24. | 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 | Baseline to week 24. | Transient Elastography will be performed at baseline and week 24 to assess the outcome. |
| The Percent of Patients Who Have Reduction of Serum Alanine Aminotransferase (ALT) by 50% | Baseline to week 24. | Blood is drawn at each time point to assess the outcome. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from physicians case load at Yale University, Digestive Disease's Liver clinic between May 2018 and December 2018. Both participants were enrolled in May of 2018.
Pre-assignment details
Of the two patients who screened, both met inclusion and exclusion criterial and were enrolled
Participants by arm
| Arm | Count |
|---|---|
| All-trans Retinoic Acid (ATRA) Therapy Fixed low dose of ATRA 10 mg twice daily for 24 weeks.
All-trans retinoic acid: Fixed low dose of ATRA 10 mg twice daily for 24 weeks. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All-trans Retinoic Acid (ATRA) Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Change of Serum Alkaline Phosphatase (ALP)
Blood will be drawn at each time point to compare pre- and post-treatment values for each individual.
Time frame: Baseline to week 24.
Population: Data were not collected
Secondary
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.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, and no trial end point was achieved so there was no data to record. .
Secondary
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.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, data not reported.
Secondary
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.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, data not reported.
Secondary
The Percent of Patients Who Have Reduction of Serum Bile Acids by 50%
Blood is drawn at each time point to assess the outcome.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, data not reported.
Secondary
The Percent of Patients Who Have Reduction of Serum C4 by 50%
Blood is drawn at each time point to assess the outcome.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, data not reported.
Secondary
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.
Time frame: Baseline to week 24.
Population: Only 1 patient completed the study, data not reported.