Overview

This trial is active, not recruiting.

Condition chronic fatigue syndrome/ myalgic encephalitis (cfs/me)
Treatments rituximab, placebo
Phase phase 3
Target CD20
Sponsor Haukeland University Hospital
Collaborator The Research Council of Norway
Start date September 2014
End date September 2017
Trial size 152 participants
Trial identifier NCT02229942, 2014-000795-25, 229035, KTS-6-2014

Summary

The hypothesis is that a subgroup of patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) have a chronically activated immune system and may benefit from B-lymphocyte treatment using the monoclonal anti-CD20 antibody rituximab with induction and maintenance treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Rituximab induction (two infusions two weeks apart) and maintenance (infusions at 3, 6, 9 and 12 months)
rituximab Rituxan
Induction with two infusions two weeks apart, rituximab 500 mg/m2 (max 1000 mg). Maintenance with rituximab infusions (500 mg fixed dose) at 3, 6, 9 and 12 months.
(Placebo Comparator)
Saline (with added albumin), two infusions two weeks apart, followed by infusions at 3, 6, 9 and 12 months.
placebo Saline
Saline (NaCl 0,9%) added human albumin (Flexbumin) 0,4 mg/ml, two infusions two weeks apart. Maintenance infusions after 3,6, 9 and 12 months.

Primary Outcomes

Measure
Fatigue score, selfreported.
time frame: Course of Fatigue score during 24 months follow-up.

Secondary Outcomes

Measure
Short Form-36 (SF-36)
time frame: Changes in SF-36 scores during 24 months follow-up
Physical activity (Sensewear armband)
time frame: Analyzed at baseline and at interval 17-21 months
Self-recorded "Function level"
time frame: Course during 24 months follow-up
Fatigue Severity Scale
time frame: 24 months
Clinical response duration
time frame: During 24 months follow-up
Sustained clinical response at 24 months
time frame: Assessment at 24 months

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) according to Canadian diagnostic criteria (Carruthers, 2003) - Duration of CFS/ME disease 2-15 years. For patients with mild CFS/ME duration of disease must be 5-15 years. - Mild, Mild/Moderate, Moderate, Moderate/Severe and Severe CFS/ME may be included - Signed informed consent Exclusion Criteria: - Patients with fatigue, who do not comply with Canadian diagnostic criteria (2003) - Duration of CFS/ME < 2 years or >15 years - Patients with very severe CFS/ME - Pregnancy or lactation. - Previous malignant disease (except basal cell carcinoma in skin or uterine cervical dysplasia) - Previous treatment with B-lymphocyte depleting therapeutic monoclonal antibodies, such as rituximab - Previous long-term systemic immunosuppressive treatment, including drugs such as cyclosporine, azathioprine, mycophenolate mofetil, but except steroid treatment e.g. for obstructive lung disease or for other autoimmune diseases such as ulcerative colitis - Severe endogenous depression - Lack of ability to adhere to protocol - Known multi-allergy with clinically assessed risk from rituximab infusion - Reduced kidney function (serum creatinine > 1,5x upper normal level) - Reduced liver function (serum bilirubin or transaminases > 1,5x upper normal level) - Known HIV positivity, previous hepatitis B or hepatitis C - Evidence of ongoing, active and clinically relevant infection - Known immunodeficiency with risk from therapeutic B-cell depletion, such as hypogammaglobulinemia

Additional Information

Official title B-lymphocyte Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Multicentre, Randomized, Double-blind and Placebo Controlled Phase-III Study With Rituximab Induction and Maintenance Treatment.
Principal investigator Olav Mella, MD, PhD
Description We have published a case series of pilot patient observations with B-cell depletion in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) (Fluge and Mella, BMC Neurol, 2009). Subsequently, we published a small randomized and double-blind phase II study using rituximab induction two infusions two weeks apart (Fluge et al, Plos One, 2011). We have completed an open label phase II study with 29 patients using rituximab induction and maintenance treatment (six rituximab infusions over 15 months, with follow-up for three years, unpublished). We hypothesize that a subgroup of patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) have a chronically activated immune system involving B-lymphocytes, possibly a variant of an autoimmune disease, and that patients may benefit from B-cell depletion therapy. Three substudies will be performed: Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months. Cardiopulmonary exercise test for two following days: assessment at baseline and repeated during the time interval 17-21 months. Gastrointestinal function: assessment at baseline and repeated during the time interval 17-21 months.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Haukeland University Hospital.