Primary Biliary CirrhosisPhase 2/3NCT00490620
Study of Combivir for Patients With Primary Biliary Cirrhosis
A Phase 2/3 study testing Combination antiviral therapy in people with Primary Biliary Cirrhosis, run by University of Alberta at 5 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Combination antiviral therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Jan 2004to Apr 2007
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 13Show fewer
- 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
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States2 sites
Mayo Clinic
Rochester, Minnesota, 55905
St Louis University
St Louis, Missouri, 63103
Canada2 sites
University of Alberta
Edmonton, Alberta, T5N 1Y9
University of Montreal
Montreal, Quebec, H3C 3J7
United Kingdom1 site
University of Birmingham
Birmingham, England, B15 2TH
About this study
Official title: Randomized Controlled Pilot Study of Combivir for Patients With Primary Biliary Cirrhosis
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
Read the 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.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- Combination antiviral therapy, Placebo
- Keywords
- primary biliary cirrhosis C06.552.630.400, retroviral infection C02.782.815
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination antiviral therapyDrug
Also called Combivir
Zidovudine 300mg and lamivudine 150mg BID for 6 months
PlaceboDrug
placebo BID for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | blinded placebo control Receives: Drug: Placebo |
| 2 | Active comparator | Antiretroviral therapy Receives: Drug: Combination antiviral therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: During the 6 months of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2007 (estimated)
- Study startJan 2004
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Axcan Pharma
- Investigators
- Andrew L Mason, MBBS MRCPI, Principal investigator, University of AlbertaBruce Bacon, MD, Principal investigator, St. Louis UniversityKeith Lindor, MD, Principal investigator, Mayo Clinic FoundationJames Neuberger, MD FRCP, Principal investigator, University of BirminghamCatherine Vincent, MD FRCPC, Principal investigator, Université de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00490620
- Sponsor's protocol ID
- Col40296
- Status last verified
- Oct 2007
- First submitted
- 21 Jun 2007
- Last updated
- 1 Nov 2007
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1111/j.1572-0241.2004.40741.x.
PubMed 15571581Mason 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.
PubMed 11825541Xu 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.
PubMed 12832623
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Pilot Study of Combivir for Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT00490620
- Acronym / sponsor ID
- Col40296
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- primary biliary cirrhosis C06.552.630.400, retroviral infection C02.782.815
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Axcan Pharma
- Study start
- Jan 2004
- Study completion
- Apr 2007 (actual)
- First posted
- 25 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placeboblinded placebo control |
| 2 | Active comparator | Drug: Combination antiviral therapyAntiretroviral therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination antiviral therapyAlso: CombivirZidovudine 300mg and lamivudine 150mg BID for 6 months | Drug | 2 |
| Placeboplacebo BID for 6 months | Drug | 1 |
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.
Time frame: During the 6 months of therapy
1 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.
Time frame: During the 6 months of therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2007.
- Background: PubMed 15571581Mason 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.
- Background: PubMed 11825541Mason 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.
- Background: PubMed 12832623Xu 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.
Related trials for Primary Biliary Cirrhosis
Active, not recruitingPhase 3
Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cirrhosis
RecruitingPhase 3
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
Primary Biliary Cholangitis
RecruitingPhase 3
FIREFLY Trial: Fenofibrate Intervention---Randomized Evaluation in First-Line PBC Therapy
Primary Biliary Cholangitis (PBC)
RecruitingPhase 3
Fenofibrate for Patients With Primary Biliary Cirrhosis Who Had An Inadequate Response to Ursodeoxycholic Acid
Primary Biliary Cirrhosis
RecruitingPhase 2/3
Fenofibrate in Patients With Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew L Mason, MBBS MRCPI principal investigator
University of Alberta
Bruce Bacon, MD principal investigator
St. Louis University
Keith Lindor, MD principal investigator
Mayo Clinic Foundation
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Combination antiviral therapy in people with Primary Biliary Cirrhosis, run by University of Alberta at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00490620, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2007.