Clinical Trials

In the current protocol, we propose the assessment of potential beneficial effects of the antibiotic Xifaxan on liver biochemistries, liver related symptoms and Mayo risk score in 15 adult and 5 pediatric patients with PSC. Adult patients will receive Xifaxan, 550 mg twice daily over a 12-week period. Pediatric patients with PSC whose weight is   greater than or equal to 40 kg will receive Xifaxan, 550 mg twice daily.

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.