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

This study has been completed.
Sponsor:
Collaborator:
PSC Partners Seeking a Cure Foundation
Information provided by (Responsible Party):
Jayant A. Talwalkar, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01085760
First received: March 10, 2010
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Primary Sclerosing Cholangitis
Drug: Vancomycin
Drug: Metronidazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change From Baseline in Alkaline Phosphatase Following 12 Weeks of Treatment [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in Total Bilirubin Following 12 Weeks Treatment [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Mayo PSC Risk Score Following 12 Weeks of Treatment [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: February 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085760

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
PSC Partners Seeking a Cure Foundation
Investigators
Principal Investigator: Jayant A Talwalkar, MD Mayo Clinic
  More Information

No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jayant A. Talwalkar, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01085760     History of Changes
Other Study ID Numbers: 08-008247
Study First Received: March 10, 2010
Results First Received: November 2, 2012
Last Updated: July 12, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cholangitis
Cholangitis, Sclerosing
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Vancomycin
Metronidazole
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Antiparasitic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 01, 2014