Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis
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| First Received Date ICMJE | October 14, 2011 | ||||||||
| Last Updated Date | June 28, 2012 | ||||||||
| Start Date ICMJE | October 2011 | ||||||||
| Estimated Primary Completion Date | October 2012 (final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Improvement in serum alkaline phosphatase levels [ Time Frame: Baseline and after 3 months of treatment. ] [ Designated as safety issue: No ] The primary outcome measure is a 30% improvement in serum alkaline phosphatase in subjects, comparing pre- and post-treatment values for each individual. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | Complete list of historical versions of study NCT01456468 on ClinicalTrials.gov Archive Site | ||||||||
| Current Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Original Secondary Outcome Measures ICMJE | Not Provided | ||||||||
| Current Other Outcome Measures ICMJE | Not Provided | ||||||||
| Original Other Outcome Measures ICMJE | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis | ||||||||
| Official Title ICMJE | Combination Therapy With Ursodeoxycholic Acid (UDCA) and All-Trans Retinoic Acid (ATRA) for Treatment of Primary Sclerosing Cholangitis - A Human Pilot Study | ||||||||
| Brief Summary | The purpose of this research study is to determine whether the combination of UDCA and ATRA taken for 3 months will improve laboratory tests of liver and bile duct inflammation in patients with PSC. Our hypothesis is that a combination of these medications will improve the liver inflammatory tests in these patients, specifically a reduction in alkaline phosphatase (AP) by at least 30%. |
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| 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. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase | Phase 1 | ||||||||
| Study Design ICMJE | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
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| Condition ICMJE | Cholangitis, Sclerosing | ||||||||
| Intervention ICMJE | Drug: Oral all-trans retinoic acid (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 IND was obtained for this process. Other Name: The medication is all-trans retinoic acid (ATRA). |
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| Study Arm (s) | Experimental: UDCA + ATRA
This is a single-arm study. All subjects will take UDCA and ATRA.
Intervention: Drug: Oral all-trans retinoic acid (ATRA) |
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| Publications * | He H, Mennone A, Boyer JL, Cai SY. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells. Hepatology. 2011 Feb;53(2):548-57. Epub 2010 Dec 10. | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE | 30 | ||||||||
| Estimated Completion Date | October 2012 | ||||||||
| Estimated Primary Completion Date | October 2012 (final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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| Gender | Both | ||||||||
| Ages | 18 Years to 80 Years | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts ICMJE |
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| Location Countries ICMJE | United States | ||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT01456468 | ||||||||
| Other Study ID Numbers ICMJE | 1012007734 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| Responsible Party | James Boyer, Yale University | ||||||||
| Study Sponsor ICMJE | Yale University | ||||||||
| Collaborators ICMJE | Mayo Clinic | ||||||||
| Investigators ICMJE |
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| Information Provided By | Yale University | ||||||||
| Verification Date | June 2012 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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