B-Cell Depleting Therapy (Rituximab) as a Treatment for Fatigue in Primary Biliary Cirrhosis

Summary

Primary Biliary Cirrhosis (PBC) is a liver disease that predominantly affects females, can present for the first time at any age and which develops over many years. It is caused by the immune system attacking the body's own tissues. People with PBC frequently experience profound fatigue or tiredness which they liken to their "batteries running down" and although people still want to undertake normal activities they often lack the energy to be able to do them. This reduces quality of life, makes it difficult for people to work and can end up with them becoming isolated in the community. At present the investigators have no treatment for fatigue in PBC. Finding a treatment for fatigue in PBC is one of the highest research priorities identified by patient groups.

The aim of this study is to undertake a clinical trial to examine the effects of a treatment ("Rituximab") on severe fatigue in PBC to help us understand whether this will be a potentially useful treatment. The information that this will give us about how energy generation changes in patients with PBC with and without the treatment will also help us to develop new treatments for fatigue in other diseases. The study has the potential to improve the quality of life of many patients with PBC, for whom there is currently no hope of improvement.

The investigators will perform a randomised controlled study of Rituximab therapy in PBC compared to placebo (1:1 ratio).

The study will be performed in a specialised clinical research environment at Clinical Research Facility Royal Victoria Infirmary. The investigators have, for many years, worked closely with PBC patient groups to focus on the problems that are important to our patients. This study is fully supported by Liver North, a liver disease charity and patient support group.

The study will take place over one year and will involve between 9 and 20 visits although a number of these will be telephone visits. Blood tests and quality of life questionnaires will be performed at the start of the study and after three, six, nine and twelve months. At baseline and 12 weeks follow up physical activity will be monitored using monitors, and an exercise test and MRI scan will be performed.

Conditions

• Fatigue
• Primary Biliary Cirrhosis

Interventions

BIOLOGICAL

Rituximab

The Rituximab dosing regimen identified is that used in the proof of concept study, which is also the established treatment regimen for Rituximab use in rheumatoid arthritis. All interventions will be administered with a clinician present throughout the infusion in participants who have been encouraged to have adequate oral hydration in the 24 hours prior to attendance. Resuscitation equipment will be immediately available during the infusion period. Blood pressure, heart rate and temperature will be monitored during the infusion. Participants will continue to be observed in the Clinical Research Facility for at least 1 hour after the infusion.

OTHER

Placebo

Participants will be randomised to Rituximab therapy (1000 mg IV on day 1 and 15) or placebo (0.9% Sodium Chloride 250 mls) control

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Department of Health, United Kingdom

  collaborator OTHER_GOV

• Newcastle University

  collaborator OTHER

• Newcastle-upon-Tyne Hospitals NHS Trust

  lead OTHER

Principal Investigators

• David EJ Jones, BA, BM, MRCP, PhD, FRCP · Faculty of Medical Sciences, Newcastle University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-10-31

Primary Completion

2016-03-31

Completion

2016-09-30

Countries

• United Kingdom

Study Locations