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

March 10, 2010
July 12, 2013
February 2010
November 2011   (final data collection date for primary outcome measure)
Change From Baseline in Alkaline Phosphatase Following 12 Weeks of Treatment [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
The primary endpoint will be the change in alkaline phosphatase following 12 weeks of treatment with each antibiotic, compared to the baseline value. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01085760 on ClinicalTrials.gov Archive Site
  • 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 ]
Frequency of adverse events, comparison of change in alkaline phosphatase, AST, total bilirubin and Mayo risk score after 12 weeks of therapy, & change in pruritus, VAS score and fatigue severity as quantified by the questionnaires compared to baseline. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis
A Pilot Study of Vancomycin or Metronidazole in Patients With Primary Sclerosing Cholangitis

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

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Primary Sclerosing Cholangitis
  • Drug: Vancomycin
    Comparison of different doses of drug
  • Drug: Metronidazole
    Comparison of different doses of drug
  • Drug: Vancomycin
    Comparison of different drug doses
  • 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.
    Interventions:
    • Drug: Vancomycin
    • Drug: Vancomycin
  • Experimental: Vancomycin 250 mg orally 4 times a day
    Intervention: Drug: Vancomycin
  • Experimental: Metronidazole 250 mg orally 3 times a day
    Intervention: Drug: Metronidazole
  • Experimental: Metronidazole 500 mg orally 3 times a day
    Intervention: Drug: Metronidazole
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
November 2011
November 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01085760
08-008247
No
Jayant A. Talwalkar, Mayo Clinic
Mayo Clinic
PSC Partners Seeking a Cure Foundation
Principal Investigator: Jayant A Talwalkar, MD Mayo Clinic
Mayo Clinic
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP