search
Back to results

Study of Combivir for Patients With Primary Biliary Cirrhosis

Primary Purpose

Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Combination antiviral therapy
Placebo
Sponsored by
University of Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring primary biliary cirrhosis C06.552.630.400, retroviral infection C02.782.815

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic
  • St Louis University
  • University of Alberta
  • University of Montreal
  • University of Birmingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

1

2

Arm Description

blinded placebo control

Antiretroviral therapy

Outcomes

Primary Outcome Measures

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 Measures

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.

Full Information

First Posted
June 21, 2007
Last Updated
October 31, 2007
Sponsor
University of Alberta
Collaborators
GlaxoSmithKline, Axcan Pharma
search

1. Study Identification

Unique Protocol Identification Number
NCT00490620
Brief Title
Study of Combivir for Patients With Primary Biliary Cirrhosis
Official Title
Randomized Controlled Pilot Study of Combivir for Patients With Primary Biliary Cirrhosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Alberta
Collaborators
GlaxoSmithKline, Axcan Pharma

4. Oversight

Data Monitoring Committee
No

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis
Keywords
primary biliary cirrhosis C06.552.630.400, retroviral infection C02.782.815

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Placebo Comparator
Arm Description
blinded placebo control
Arm Title
2
Arm Type
Active Comparator
Arm Description
Antiretroviral therapy
Intervention Type
Drug
Intervention Name(s)
Combination antiviral therapy
Other Intervention Name(s)
Combivir
Intervention Description
Zidovudine 300mg and lamivudine 150mg BID for 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo BID for 6 months
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew L Mason, MBBS MRCPI
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bruce Bacon, MD
Organizational Affiliation
St. Louis University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Keith Lindor, MD
Organizational Affiliation
Mayo Clinic Foundation
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Neuberger, MD FRCP
Organizational Affiliation
University of Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Catherine Vincent, MD FRCPC
Organizational Affiliation
Université de Montréal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
St Louis University
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63103
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T5N 1Y9
Country
Canada
Facility Name
University of Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3C 3J7
Country
Canada
Facility Name
University of Birmingham
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
15571581
Citation
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.
Results Reference
background
PubMed Identifier
11825541
Citation
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.
Results Reference
background
PubMed Identifier
12832623
Citation
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.
Results Reference
background

Learn more about this trial

Study of Combivir for Patients With Primary Biliary Cirrhosis

We'll reach out to this number within 24 hrs