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Study of Combivir for Patients With Primary Biliary Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00490620
Recruitment Status : Completed
First Posted : June 25, 2007
Last Update Posted : November 1, 2007
Axcan Pharma
Information provided by:
University of Alberta

Brief Summary:
This is a proof of principal study to determine whether combination anti-viral therapy with Combivir impacts on hepatic biochemistry in patients with primary biliary cirrhosis

Condition or disease Intervention/treatment Phase
Primary Biliary Cirrhosis Drug: Combination antiviral therapy Drug: Placebo Phase 2 Phase 3

Detailed Description:
A novel human retrovirus has been cloned from a cDNA library derived from biliary epithelia cells extracted from patients with Primary Biliary Cirrhosis. Although there is no formal proof that this virus is etiologically related to the disease, we have found evidence for viral infection in the majority of patients with PBC using standard serologic and hybridization assays. In order to address the hypotheses that PBC is etiologically related to a retrovirus infection and that anti-retroviral therapy may be beneficial for patients with PBC, we have conducted 2 pilot studies using lamivudine and Combivir (lamivudine 150mg and Zidovudine 300mg). On the whole, little clinical improvement was observed in patients on lamivudine therapy alone, whereas those on Combivir had significant reductions of hepatic biochemistry studies and histologic improvement. Moreover, 4 of 10 Combivir patients completely normalized their liver function tests and the anti-viral therapy was well tolerated. We now propose a larger randomized trial to assess the short term (6 months) safety and efficacy of Combivir for patients with PBC. Efficacy in this study will be defined using both liver biochemistries and virologic endpoints.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Pilot Study of Combivir for Patients With Primary Biliary Cirrhosis
Study Start Date : January 2004
Actual Study Completion Date : April 2007

Arm Intervention/treatment
Placebo Comparator: 1
blinded placebo control
Drug: Placebo
placebo BID for 6 months

Active Comparator: 2
Antiretroviral therapy
Drug: Combination antiviral therapy
Zidovudine 300mg and lamivudine 150mg BID for 6 months
Other Name: Combivir

Primary Outcome Measures :
  1. The percentage of patients with either (i) normalized alkaline phosphatase, (ii) normalized AST and ALT or (iii) normal alkaline phosphatase, AST and ALT will be recorded. [ Time Frame: During the 6 months of therapy ]

Secondary Outcome Measures :
  1. 50% improvement towards baseline for alkaline phosphatase, AST and ALT, changes in symptoms using an objective graded clinical parameter scale, serum AMA titers, quantitative immunoglobulins and virologic parameters. [ Time Frame: During the 6 months of therapy ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients 18 years old of either sex will be recruited for this study.
  • Persistently elevated alkaline phosphatase or serum aminotransferases of at least 1.5 times normal after a minimum of 6 months UDCA therapy.
  • Positive serum AMA (titer > 1:20).
  • Liver biopsy histology compatible with PBC obtained at any time prior to study.
  • Maintained on UDCA at a dose of 13-15 mg/kg for 6 or more months.
  • Patients must read and sign informed consent form.

Exclusion Criteria:

  • Patients treated with immunosuppressive or anti-inflammatory agents such as colchicine, methotrexate, D-penicillamine, cyclosporine, tacrolimus, mycophenolate mofetil, corticosteroid therapy will be excluded but may enter the study after a 3 month period off immunosuppressive and anti-inflammatory therapy.
  • Advanced liver disease: Childs Pugh class B or C cirrhosis, recurrent variceal hemorrhage, spontaneous encephalopathy, diuretic resistant ascites, need for liver transplantation within the year.
  • Patients with a secondary hepatic diagnosis such as viral hepatitis, drug induced liver injury, extrahepatic biliary obstruction, primary sclerosing cholangitis, metabolic liver diseases or alcoholic liver disease.
  • Regular use of more than 30 g of alcohol per day in the last year.
  • Patients with a predicted survival of less than 3 years from malignant or other potentially life threatening disease.
  • Creatinine clearance less than < 70 mL/min using the Cockcroft Gault equation:
  • Clinically apparent pancreatitis.
  • Serum amylase > 3 x upper limit of normal (patients with sicca syndrome and salivary gland disease may have elevated amylase levels)
  • Pregnancy or breast-feeding a child.
  • Sexually active patients of child bearing age and not using effective contraception.
  • Allergic reaction to Combivir like drugs
  • Clinical evidence of myositis
  • Weight of < 50 Kg

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00490620

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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
St Louis University
St Louis, Missouri, United States, 63103
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T5N 1Y9
Canada, Quebec
University of Montreal
Montreal, Quebec, Canada, H3C 3J7
United Kingdom
University of Birmingham
Birmingham, England, United Kingdom, B15 2TH
Sponsors and Collaborators
University of Alberta
Axcan Pharma
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Principal Investigator: Andrew L Mason, MBBS MRCPI University of Alberta
Principal Investigator: Bruce Bacon, MD St. Louis University
Principal Investigator: Keith Lindor, MD Mayo Clinic Foundation
Principal Investigator: James Neuberger, MD FRCP University of Birmingham
Principal Investigator: Catherine Vincent, MD FRCPC Université de Montréal
Layout table for additonal information Identifier: NCT00490620    
Other Study ID Numbers: Col40296
First Posted: June 25, 2007    Key Record Dates
Last Update Posted: November 1, 2007
Last Verified: October 2007
Keywords provided by University of Alberta:
primary biliary cirrhosis C06.552.630.400
retroviral infection C02.782.815
Additional relevant MeSH terms:
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Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Bile Duct Diseases
Biliary Tract Diseases
Antiviral Agents
Anti-Infective Agents