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

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

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Vancomycin; Drug: Vancomycin; Drug: Metronidazole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin 125 mg orally 4 times a day; 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; Comparison of different doses of drug; Drug: Vancomycin; Comparison of different drug doses
Experimental: Vancomycin 250 mg orally 4 times a day	Drug: Vancomycin; Comparison of different doses of drug; Drug: Vancomycin; Comparison of different drug doses
Experimental: Metronidazole 250 mg orally 3 times a day	Drug: Metronidazole; Comparison of different doses of drug
Experimental: Metronidazole 500 mg orally 3 times a day	Drug: Metronidazole; Comparison of different doses of drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: PSC Partners Seeking a Cure
• Investigators: Principal Investigator: Jayant A Talwalkar, MD, Mayo Clinic

Publications and helpful links

General Publications

• Tabibian JH, Weeding E, Jorgensen RA, Petz JL, Keach JC, Talwalkar JA, Lindor KD. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis - a pilot study. Aliment Pharmacol Ther. 2013 Mar;37(6):604-12. doi: 10.1111/apt.12232. Epub 2013 Feb 5.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 10, 2010
• First Submitted That Met QC Criteria: March 10, 2010
• First Posted (Estimate): March 12, 2010

Study Record Updates

• Last Update Posted (Estimate): September 19, 2013
• Last Update Submitted That Met QC Criteria: July 12, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Vancomycin; Metronidazole
• Other Study ID Numbers: 08-008247