Study of Combivir for Patients With Primary Biliary Cirrhosis
Information source: University of Alberta
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Primary Biliary Cirrhosis
Intervention: Combination antiviral therapy (Drug); Placebo (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: University of Alberta Official(s) and/or principal investigator(s):
Andrew L Mason, MBBS MRCPI, Principal Investigator, Affiliation: University of Alberta
Bruce Bacon, MD, Principal Investigator, Affiliation: St. Louis University
Keith Lindor, MD, Principal Investigator, Affiliation: Mayo Clinic Foundation
James Neuberger, MD FRCP, Principal Investigator, Affiliation: University of Birmingham
Catherine Vincent, MD FRCPC, Principal Investigator, Affiliation: University of Montreal
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
Clinical Details
Official title: Randomized Controlled Pilot Study of Combivir for Patients With Primary Biliary Cirrhosis
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: 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.
Secondary outcome: 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.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University of Alberta, Edmonton, Alberta T5N 1Y9, Canada
University of Birmingham, Birmingham, England B15 2TH, United Kingdom
Mayo Clinic, Rochester, Minnesota 55905, United States
St Louis University, St Louis, Missouri 63103, United States
University of Montreal, Montreal, Quebec H3C 3J7, Canada
Additional Information
Related publications: Mason AL, Farr GH, Xu L, Hubscher SG, Neuberger JM. Pilot studies of single and combination antiretroviral therapy in patients with primary biliary cirrhosis. Am J Gastroenterol. 2004 Dec;99(12):2348-55. Mason A, Nair S. Primary biliary cirrhosis: new thoughts on pathophysiology and treatment. Curr Gastroenterol Rep. 2002 Feb;4(1):45-51. Review. Xu L, Shen Z, Guo L, Fodera B, Keogh A, Joplin R, O'Donnell B, Aitken J, Carman W, Neuberger J, Mason A. Does a betaretrovirus infection trigger primary biliary cirrhosis? Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8454-9. Epub 2003 Jun 27.
Starting date: January 2004
Ending date: April 2007
Last updated: October 31, 2007
|
