A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Vancomycin or Metronidazole is safe and beneficial in the treatment of Primary Sclerosing Cholangitis.

Detailed Description
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In this protocol, we propose the assessment of potential beneficial effects of the antibiotics vancomycin and metronidazole on liver biochemistries, liver related symptoms and Mayo risk score in patients with PSC. The patients will be randomized into four groups of ten patients: one group will receive low dose vancomycin, one group will receive high dose vancomycin, one group will receive low dose metronidazole and one group will receive high dose metronidazole. Each group will be treated for three months.

Official Title
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A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Drug: Vancomycin
* Drug: Vancomycin
* Drug: Metronidazole
* Drug: Metronidazole
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PSC established by alkaline phosphatase >1.5 times and/or two fold elevation of liver transaminases (AST and/or ALT) for at least 6 months duration. Cholangiography demonstrating intrahepatic and/or extrahepatic biliary obstruction, beading, or narrowing consistent with PSC. Both genders. Age ≥ 18 years old and < than 75 years old. 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, silymarin or prednisone in the preceding three months. Active drug or alcohol use. Prior history of allergic reactions to the antibiotics which will be used in the study. Any condition that, in the opinion of the investigator, would interfere with the patients' 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. Pregnancy or current lactation. Subjects becoming pregnant during the study will be withdrawn.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycin 125 mg orally 4 times a day<br>The patients will be randomized into four groups of ten patients: one group will receive low dose vancomycin, one group will receive high dose vancomycin, one group will receive low dose metronidazole and one group will receive high dose metronidazole. | Drug: Vancomycin<br>* Comparison of different doses of drug<br>Drug: Vancomycin<br>* Comparison of different drug doses<br>|
| Experimental: Vancomycin 250 mg orally 4 times a day<br> | Drug: Vancomycin<br>* Comparison of different doses of drug<br>|
| Experimental: Metronidazole 250 mg orally 3 times a day<br> | Drug: Metronidazole<br>* Comparison of different doses of drug<br>|
| Experimental: Metronidazole 500 mg orally 3 times a day<br> | Drug: Metronidazole<br>* Comparison of different doses of drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Alkaline Phosphatase Following 12 Weeks of Treatment |  | baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Bilirubin Following 12 Weeks Treatment |  | baseline, 12 weeks | 
| Change From Baseline in Mayo PSC Risk Score Following 12 Weeks of Treatment | The Mayo PSC risk score was calculated for each patient at baseline and at 12 weeks, where Risk = 0.03 (age [years]) + 0.54 Ln (total bilirubin [mg/dL]) + 0.54 Ln (AST [IU/L]) + 1.24 (variceal bleeding) - 0.84 (albumin [g/dL]). There is no range, minimum, or maximum value but greater values indicate worse disease. | baseline, 12 weeks | 
| Change From Baseline in C-Reactive Protein Following 12 Weeks of Treatment |  | baseline, 12 weeks |