Condition category
Digestive System
Date applied
12/09/2003
Date assigned
12/09/2003
Last edited
15/11/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr JM Neuberger

ORCID ID

Contact details

Liver Medicine
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0265092544

Study information

Scientific title

Acronym

Study hypothesis

This study will further test the hypothesis that there is an infectious aetiology involved in the development of primary biliary cirrhosis (PBC) by undertaking a randomised, controlled, phase II pilot study of Combivir® therapy in patients with PBC.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Primary biliary cirrhosis (PBC)

Intervention

This investigation is designed as a randomised, controlled, phase II pilot study of Combivir® in approximately 60 patients with PBC. It is expected that the majority of PBC patients will already be taking ursodeoxycholic acid and patients enrolled in the study will have been on this treatment for at least 6 months.

Patients will be randomised to continue with ursodeoxycholic acid alone or in combination with Combivir®. The clinical, virological, histological and immune effects of the study drug will be examined. The clinical end point of the study will be 1 year of therapy or evidence for developing end stage liver disease. All PBC patients except for those with decompensated liver disease will be enrolled in the study after obtaining an informed written consent.

The PBC patients will already be on ursodeoxycholic acid at an adjusted dose of 13 - 15 mg/kg of body weight/day in 2 - 3 divided doses. Patients treated with Combivir® will receive one tablet twice a day: Lamivudine 150 mg and Zidovudine 300 mg twice a day. Those patients not on ursodeoxycholic acid at the start of the study will be treated with ursodeoxycholic acid at the dose indicated for a period of 6 months prior to randomisation to ursodeoxycholic acid alone or in combination with Combivir® twice a day.

At enrolment, each patient with PBC will be assessed for the inclusion criteria. Prior to therapy, patients will have a thorough history taken to assess symptoms. An objective graded clinical parameter scale will include the development, presence or worsening of pruritus, fatigue, sicca syndrome or right upper quadrant pain. At the same time patients will be examined for the presence or development of overt clinical signs such as jaundice, splenomegaly or hepatomegaly. At this point, the baseline blood tests will include: full blood count (FBC), reticulocyte count, prothrombin time (PT), erythrocyte sedimentation rate (ESR), blood urea nitrogen (BUN), creatinine, sodium, potassium, calcium, phosphate, albumin, total protein, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, creatine kinase (CK), amylase, immunoglobulins, antinuclear antibodies (ANA), and quantitated AMA. All of these are laboratory assessments that are clinically useful in following patients with PBC.

Unless problems develop in the interim, patients will be seen at months 1, 3, 6, 9 and 12 after initiation of therapy. At the initial clinic visit, blood will be drawn for BUN, creatinine, electrolytes, amylase, bilirubin, AST, ALT, alkaline phosphatase, albumin, PT, serum lactate and FBC. Subsequently, samples will be drawn for hepatic biochemistry, as well as virological and immunological studies. Patients will undergo a physical exam at each visit and also be questioned about changes in symptoms. Liver biopsies will be performed as clinically indicated.

Response to therapy will be based on changes in symptomatology, development of overt clinical signs, immunological parameters, improvement of liver function and biochemistry. Immunological studies include quantitative AMA levels. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot virological studies will be performed on serum samples before and after therapy in the Hepatitis Research Laboratory, Alton Ochsner Medical Foundation, USA.

Intervention type

Drug

Phase

Not Applicable

Drug names

Ursodeoxycholic acid, Combivir® (lamivudine and zidovudine)

Primary outcome measures

Not provided at time of registration

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/10/2001

Overall trial end date

01/05/2005

Reason abandoned

Eligibility

Participant inclusion criteria

Patients will be recruited from the Liver Out-Patients Department at the Queen Elizabeth Hospital:
1. Patients greater than 20 years old of either sex
2. Elevated alkaline phosphatase or alanine aminotransferase (ALT) within 3 months prior to the start of therapy
3. Positive serum anti-mitochondrial antibodies (AMA) (titre greater than 1:20)
4. Liver biopsy histology compatible with PBC

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Patients treated with immunosuppressive or anti-inflammatory agents
2. Advance liver disease: Child's class B or C
3. Patients with secondary hepatological diagnosis
4. Alcohol abuse (greater than 50 g of alcohol per day)
5. Other significant co-morbidity (e.g. cardiac or renal failure)
6. Pregnancy or breast feeding
7. Sexually active female of child bearing age not using effective contraception

Recruitment start date

01/10/2001

Recruitment end date

01/05/2005

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Liver Medicine
Birmingham
B15 2TH
United Kingdom

Sponsor information

Organisation

Department of Health (UK)

Sponsor details

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom

Sponsor type

Government

Website

http://www.doh.gov.uk

Funders

Funder type

Industry

Funder name

University Hospital Birmingham NHS Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NHS R&D Support Funding

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

GlaxoSmithKline (GSK) (UK)

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2004 results in http://www.ncbi.nlm.nih.gov/pubmed/15571581

Publication citations

  1. Results

    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, 99, 12, 2348-2355, doi: 10.1111/j.1572-0241.2004.40741.x.

Additional files

Editorial Notes