A Pilot Study of Xifaxan to Treat Patients With PSC

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of Xifaxan in Patients With Primary Sclerosing Cholangitis

Conditions
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Primary Sclerosing Cholangitis (PSC)

Intervention / Treatment
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* Drug: Xifaxan


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of PSC established by all of the following criteria: Alkaline phosphatase >1.5 times upper limit of normal for at least 6 months duration Gamma-glutamyl transferase (GGT) >1.5 times upper limit of normal in pediatric patients Cholangiography demonstrating intrahepatic and/or extrahepatic biliary obstruction, beading, or narrowing consistent with PSC Liver histology in the past (if available for review) with features consistent with or diagnostic of PSC Both genders Adults: Ages 18-75 years. Pediatric: Weight > 40 kg Patient's informed consent for study participation Exclusion criteria: Treatment with systematic antibiotics, Azulfidine, ursodeoxycholic acid, corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, tacrolimus, vitamin E or prednisone in the preceding three months Active drug or alcohol use Prior history of allergic reaction to the antibiotics which will be used in the study Any condition that, in the opinion of the investigator, would interfere with the patient's ability to complete the study safely or successfully Evidence of decompensated liver disease such as recurrent variceal bleeding, refractory ascites or spontaneous hepatic encephalopathy Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant) Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis or secondary sclerosing cholangitis Treatment with any study medications in the preceding three months Pregnancy or current lactation; subjects becoming pregnant during the study despite all the precautions will be withdrawn and referred to their primary physicians

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xifaxan<br>Xifaxan 550 mg two times per day for three months | Drug: Xifaxan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in alkaline phosphatase | An improvement in elevated levels of alkaline phosphatase to less than half of the initial level at study entry | Three months | 
| Absence of treatment failure | Absence of treatment failure which is defined as any of the following: death, need for liver transplantation, side effects requiring discontinuation of therapy, worsening of liver biochemistries, voluntary discontinuation for any reason, marked worsening of fatigue or itching. | Three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Sclerosing Cholangitis, Xifaxan