Back to resultsA Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis (PSC)
Primary Purpose
Primary Sclerosing Cholangitis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Vancomycin
Vancomycin
Metronidazole
Metronidazole
Vancomycin
Sponsored by
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis
Eligibility Criteria
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 Subjects becoming pregnant during the study will be withdrawn.
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Vancomycin 125 mg orally 4 times a day
Vancomycin 250 mg orally 4 times a day
Metronidazole 250 mg orally 3 times a day
Metronidazole 500 mg orally 3 times a day
Arm Description
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.
Outcomes
Primary Outcome Measures
Change From Baseline in Alkaline Phosphatase Following 12 Weeks of Treatment
Secondary Outcome Measures
Change From Baseline in Total Bilirubin Following 12 Weeks Treatment
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.
Change From Baseline in C-Reactive Protein Following 12 Weeks of Treatment
Full Information
NCT ID
NCT01085760
First Posted
March 10, 2010
Last Updated
July 12, 2013
Sponsor
Mayo Clinic
Collaborators
PSC Partners Seeking a Cure
1. Study Identification
Unique Protocol Identification Number
NCT01085760
Brief Title
A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis
Acronym
PSC
Official Title
A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
PSC Partners Seeking a Cure
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vancomycin 125 mg orally 4 times a day
Arm Type
Experimental
Arm Description
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.
Arm Title
Vancomycin 250 mg orally 4 times a day
Arm Type
Experimental
Arm Title
Metronidazole 250 mg orally 3 times a day
Arm Type
Experimental
Arm Title
Metronidazole 500 mg orally 3 times a day
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Intervention Description
Comparison of different doses of drug
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Intervention Description
Comparison of different doses of drug
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Intervention Description
Comparison of different doses of drug
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Intervention Description
Comparison of different doses of drug
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Intervention Description
Comparison of different drug doses
Primary Outcome Measure Information:
Title
Change From Baseline in Alkaline Phosphatase Following 12 Weeks of Treatment
Time Frame
baseline, 12 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Total Bilirubin Following 12 Weeks Treatment
Time Frame
baseline, 12 weeks
Title
Change From Baseline in Mayo PSC Risk Score Following 12 Weeks of Treatment
Description
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.
Time Frame
baseline, 12 weeks
Title
Change From Baseline in C-Reactive Protein Following 12 Weeks of Treatment
Time Frame
baseline, 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jayant A Talwalkar, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23384404
Citation
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.
Results Reference
derived
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A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis
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