- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01456468
Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis
Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis - A Human Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with PSC often have ongoing inflammation and fibrosis (scars) along the length of their bile ducts, and eventually this involves the liver itself which can lead to cirrhosis (severe scarring), severe infections (cholangitis), bile duct cancer and death.
Although many patients are treated with UDCA, and experience improvement in their liver tests and relief of symptoms, no medical treatment to date has been found to produce a long-term improvement of inflammation and scarring, or to improved survival. For this reason, there is a great need to identify new medications which are effective for the treatment of PSC.
Recent work in animals by the research group at Yale University School of Medicine has shown that the combination of UDCA and ATRA produced a significant improvement in liver scarring and inflammation in animals with bile duct disease similar to that seen in PSC. This improvement included a lowering in the levels of bile acids, which are harmful to the liver, and a lowering of inflammation in the liver tissue of these animals. The benefits seen in this study were greater in animals receiving the combination of UDCA and ATRA compared to animals who received either medicine alone.
The medication ATRA is related to vitamin A, and has been used for many years as a topical medication in the treatment of skin conditions such as acne and psoriasis. It has also been used for nearly 20 years as an oral medicine in the treatment of a form of blood cancer (acute promyelocytic leukemia), where it is given for 90 days at a time. ATRA has been shown to produce a remission from the leukemia and is currently a standard treatment for patients with that specific condition. ATRA is not used routinely in the care of patients with liver or bile duct disease.
Based on the benefits observed by treatment with ATRA and UDCA in our animal studies, the investigators plan to study this combination in patients with PSC and believe that this may be an effective regimen for patients with this condition. The investigators will check blood tests of the liver and bile ducts before, during, and after the treatment in order to look for changes to liver tests which would be due to the medication combination.
Therefore, the goal of this study is to study the changes to liver tests in patients with PSC who take a combination of UDCA and ATRA for 90 days, comparing levels at the beginning of the study to those at the end of the study.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
- Yale University School of Medicine - 333 Cedar St - 1080 LMP
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of PSC for at least 6 months, made by clinical evaluation in addition to one of the following: a prior endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC, also termed MRI/MRCP) or liver biopsy.
Progressing disease or stable disease with persistent elevation in AP despite treatment with UDCA (15 mg/kg/day) for at least 6 months.
Measures of progressing disease:
- Cholangitis within the past 12 months.
- Presence or progression of biliary abnormalities on MRI/MRC.
- Elevated liver tests (alkaline phosphatase, bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]).
- Age between 18 and 80.
Exclusion Criteria:
- Pregnancy or planned pregnancy during study period and within 6 months of study completion.
- Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher cardiac disease, hyperlipidemia, hypertriglyceridemia, hepatic injury, or adverse event related to administration of UDCA or ATRA.
- Prior intolerance to UDCA or ATRA (or related oral vitamin A compounds).
- Evidence of decompensated cirrhosis within the past 6 months (i.e. variceal bleeding, uncontrolled ascites, hepatic encephalopathy, jaundice).
- Estimated need for liver transplantation within 1 year.
- Any evidence of hepatocellular carcinoma, cholangiocarcinoma, or other malignancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: UDCA + ATRA
This is a single-arm study.
All subjects will take UDCA and ATRA.
|
The subjects will continue to take their current dose of UDCA (15 mg/kg/day), as per ongoing clinical care, and need to be on a stable dose of UDCA for at least six months prior to enrollment. The specific intervention is the addition of daily oral ATRA (45 mg/m^2) divided into 2 doses. To increase adherence to the dosing regimen, the drug will be compounded by the Research Pharmacies of Yale and Mayo into 2 formulations (30 mg and 40 mg capsules), and an Investigational New Drug (IND) permit was obtained for this process.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Improvement in serum alkaline phosphatase levels
Time Frame: Baseline and after 3 months of treatment.
|
The primary outcome measure is a 30% improvement in serum alkaline phosphatase in subjects, comparing pre- and post-treatment values for each individual.
|
Baseline and after 3 months of treatment.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: James L Boyer, MD, Yale University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1012007734
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cholangitis, Sclerosing
-
Medical University of WarsawNational Science Centre, PolandRecruitingPrimary Sclerosing Cholangitis (PSC)Poland
-
Mayo ClinicActive, not recruiting
-
Cascade Pharmaceuticals, IncCovanceCompletedPrimary Sclerosing Cholangitis (PSC)United States
-
Brigham and Women's HospitalCompletedSclerosing CholangitisUnited States
-
RenJi HospitalRecruitingPrimary Sclerosing Cholangitis | IgG4-related Sclerosing CholangitisChina
-
HighTide Biopharma Pty LtdCompletedPrimary Sclerosing Cholangitis (PSC)United States, Canada
-
Intercept PharmaceuticalsCompletedPrimary Sclerosing Cholangitis (PSC)United States, Italy
-
Mirum Pharmaceuticals, Inc.CompletedPrimary Sclerosing Cholangitis (PSC)United States, United Kingdom, Canada
-
Mayo ClinicCompletedPrimary Sclerosing Cholangitis (PSC)United States
-
Gilead SciencesCompletedPrimary Sclerosing Cholangitis (PSC)United States, Belgium, Canada, Germany, United Kingdom, Italy, Spain, Denmark, Netherlands, Sweden
Clinical Trials on Oral all-trans retinoic acid (ATRA)
-
Amsterdam UMC, location VUmcUMC Utrecht; Erasmus Medical Center; University of Turin, Italy; Vejle HospitalCompleted
-
Shandong UniversityWithdrawnPurpura | Idiopathic Thrombocytopenic PurpuraChina
-
Gruppo Italiano Malattie EMatologiche dell'AdultoUnknown
-
Gruppo Italiano Malattie EMatologiche dell'AdultoUnknown
-
Peking University People's HospitalQilu Hospital of Shandong University; Beijing Hospital; Navy General Hospital...Unknown
-
Dwight OwenRecruitingMetastatic Lung Non-Small Cell Carcinoma | Stage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Recurrent Lung Non-Small Cell CarcinomaUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedLung CancerUnited States
-
First Affiliated Hospital Xi'an Jiaotong UniversityRecruitingAcute Myeloid LeukemiaChina
-
Imago BioSciences, Inc., a subsidiary of Merck...CompletedAcute Myeloid Leukemia | Myelodysplastic SyndromeAustralia
-
Peking University People's HospitalBeijing Friendship Hospital; Beijing Tongren Hospital; Beijing Hospital; Navy General...Not yet recruitingPurpura, Thrombocytopenic, IdiopathicChina