Fatigue Clinical Trial
— RITPBCOfficial title:
B-Cell Depleting Therapy (Rituximab) as a Treatment for Fatigue in Primary Biliary Cirrhosis
Verified date | January 2017 |
Source | Newcastle-upon-Tyne Hospitals NHS Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 71 |
Est. completion date | September 2016 |
Est. primary completion date | March 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - age = 18 years - patient has capacity and provided written informed consent for participation in the study prior to any study specific procedures - moderate or severe fatigue as assessed using previously designated cut-offs of the PBC-40 fatigue domain (i.e. fatigue domain score >33) - presence of AMA (anti-PDH antibody) at a titre of >1:40 - adequate haematological function Hb >9g/L, Absolute neutrophil count >1.5x109/L, platelet count > 50x109/L - bilirubin = 50 µmol - INR = 1.5 - Child-Pugh score < 7 - ECOG performance status < 2 - adequate renal function; Cockroft and Gault estimation > 40ml/min - women of childbearing potential should have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 12 months after completion of treatment. Acceptable forms of effective contraception include: - established use of oral, injected or implanted hormonal methods of contraception - placement of an intrauterine device (IUD) or intrauterine system (IUS) - barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository - male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) - true abstinence: when this is in line with the preferred and usual lifestyle of the subject Exclusion Criteria: - advanced or decompensated disease (variceal bleed, hepatic encephalopathy or ascites) - history or presence of other concomitant liver diseases (including hepatitis due to hepatitis B (surface antigen positive or core antibody positive) or C or evidence of chronic viraemia on baseline screening), primary sclerosing cholangitis or biopsy proven non-alcoholic steatohepatitis) - average alcohol ingestion >21 units/week (male) or >14 units / week (female) - chronic sepsis or intercurrent condition likely to predispose to chronic sepsis during the study - previous treatment with B-cell depleting therapy - previous history of aberrant response or intolerance to immunological agents - presence of significant untreated intercurrent medical condition itself associated with fatigue - presence of significant risk of depressive illness (HADS score indicating caseness) - current statin therapy or statin use within 3 months of enrolment - ongoing participation in other clinical trials or exposure to any investigational agent 4 weeks prior to baseline or within < 5 half lives of the investigational drug - major surgery within 4 weeks of study entry - vaccination within 4 weeks of study entry; patients requiring seasonal flu or travel vaccines will be required to wait a minimum of 4 weeks post vaccination to enrol in the study - pregnant or lactating women - psychiatric or other disorder likely to impact on informed consent - patient is unable and/or unwilling to comply with treatment and study instructions - any other medical condition that, in the opinion of the investigator would interfere with safe completion of the study - hypersensitivity to the active substance (Rituximab) or to any of the excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water (for infusion)) or to murine proteins - active, severe infections (e.g. tuberculosis, sepsis or opportunistic infections) - known HIV infection - clinical history of latent TB infection unless the patient has completed adequate antibiotic prophylaxis - AST/ALT 4 x upper limit of normal - severe immune-compromised state - severe heart failure (NYHA Class IV) or severe uncontrolled cardiac disease - malignancy (other than basal cell carcinoma) within the last 10 years - demyelinating disease - previous participation in this study - any contraindication to Rituximab therapy not covered by other exclusions |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Newcastle Clinical Trials Unit | Newcastle upon Tyne | Tyne and Wear |
Lead Sponsor | Collaborator |
---|---|
Newcastle-upon-Tyne Hospitals NHS Trust | Department of Health, United Kingdom, National Institute for Health Research, United Kingdom, Newcastle University |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Fatigue severity in PBC patients, assessed using the fatigue domain of the PBC-40, a fully validated, psychometrically robust, disease specific quality of life measure | Between baseline and 12 week assessment | ||
Secondary | Improvement in physical activity assessed using seven day physical activity monitoring | 12 weeks | ||
Secondary | Assessment of improvement in daytime somnolence, vasomotor autonomic symptoms, functional status, reduction in depressive and anxiety-related symptoms | All assessments will be using questionnaires that currently are used in the routine clinical setting. | 12 weeks | |
Secondary | Reduction in serum anti-pyruvate dehydrogenase complex antibody levels and in numbers of peripheral blood B-cells | This is to confirm whether any clinical effect is directly related to antibody modulation. | 12 months | |
Secondary | Improvement in peripheral muscle bio-energetic function on exercise | This is to confirm whether any clinical effect is directly related to effects on muscle bioenergetic function. | 12 weeks |
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