Study of Combivir for Patients With Primary Biliary Cirrhosis

NCT00490620 | Completed Phase 2

• 1 other identifier: Col40296
• Study Type: interventional
• Target: 59
• Locations: 3 countries
• Sites: 5

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

Conditions

Primary Biliary Cirrhosis

Keywords

primary biliary cirrhosis C06.552.630.400; retroviral infection C02.782.815

Outcome Measures

Primary Outcomes (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.

  During the 6 months of therapy

Secondary Outcomes (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.

  During the 6 months of therapy

Study Arms (2)

1

PLACEBO COMPARATOR

blinded placebo control

Drug: Placebo

2

ACTIVE COMPARATOR

Antiretroviral therapy

Drug: Combination antiviral therapy

Interventions

Combination antiviral therapy DRUG

Zidovudine 300mg and lamivudine 150mg BID for 6 months

Also known as: Combivir

2

Placebo DRUG

placebo BID for 6 months

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead
• GlaxoSmithKline: collaborator
• Axcan Pharma: collaborator

Study Sites (5)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St Louis University

St Louis, Missouri, 63103, United States

Location

University of Alberta

Edmonton, Alberta, T5N 1Y9, Canada

Location

University of Montreal

Montreal, Quebec, H3C 3J7, Canada

Location

University of Birmingham

Birmingham, England, B15 2TH, United Kingdom

Location

Related Publications (3)

• 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. doi: 10.1111/j.1572-0241.2004.40741.x.

  PMID: 15571581 BACKGROUND

• Mason A, Nair S. Primary biliary cirrhosis: new thoughts on pathophysiology and treatment. Curr Gastroenterol Rep. 2002 Feb;4(1):45-51. doi: 10.1007/s11894-002-0037-8.

  PMID: 11825541 BACKGROUND

• 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. doi: 10.1073/pnas.1433063100. Epub 2003 Jun 27.

  PMID: 12832623 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

lamivudine, zidovudine drug combination

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 21, 2007
• First Posted: June 25, 2007
• Study Start: January 1, 2004
• Study Completion: April 1, 2007
• Last Updated: November 1, 2007

Record last verified: 2007-10

Locations

US (2); GB (1); CA (2)