Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME) Clinical Trial
— RituxMEOfficial 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.
| Verified date | February 2018 |
| Source | Haukeland University Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 151 |
| Est. completion date | November 2017 |
| Est. primary completion date | September 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Norway | Dept. of Oncology, Haukeland University Hospital | Bergen | |
| Norway | Notodden Hospital | Notodden | |
| Norway | CFS/ME centre, Oslo University Hospital | Oslo | |
| Norway | Division of Rehabilitation Services, University Hospital of North Norway | Tromsø | |
| Norway | Dept. of Pain and Complex Disorders, St. Olavs Hospital | Trondheim |
| Lead Sponsor | Collaborator |
|---|---|
| Haukeland University Hospital | MEandYou Foundation, Norwegian Department of Health and Social Affairs, Oslo University Hospital, Sykehuset Telemark, The Kavli Foundation, The Norwegian ME association, The Research Council of Norway, Trondheim University Hospital, University Hospital of North Norway |
Norway,
Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H, Mella O. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358. Epub 2011 Oct 19. — View Citation
Fluge Ø, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Toxicity and side-effects | Toxicity and side effects will be recorded throughout 24 months follow-up, as specified in the protocol. | During 24 months follow-up | |
| Primary | Fatigue score, selfreported. | Selfreported Fatigue score is registered every second week, as the mean score for the four symptoms: "Post-exertional malaise", "Fatigue", "Need for rest", "Daily functioning" (scale 0-6). Mean Fatigue scores for the time intervals 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 months are recorded for each patient. These data are used for statistical analysis. The difference in course of Fatigue score during 24 months follow-up, between the rituximab and placebo groups, will constitute the primary endpoint.
Overall response is recorded as the effect on CFS/ME symptoms during 24 months follow-up. The overall response is not predefined to a specific time interval, but is defined as mean Fatigue score at least 4.5 for at least 8 consecutive weeks for moderate response, and mean Fatigue score at least 5.0 for at least 8 consecutive weeks for major response. Single response periods and the sum of response periods during 24 months follow-up will be recorded. |
Course of Fatigue score during 24 months follow-up. | |
| Secondary | Short Form-36 (SF-36) | SF-36 (ver 1.2) are selfreported by patients at baseline, and at 3, 6, 9, 12, 15, 18, 21 and 24 months follow-up. Changes in Physical health summary score, Physical function, and "Mean of five subdimensions" (Physical function, Bodily pain, Vitality, Social function, General health) are recorded. The difference in course during 24 months follow-up, between the rituximab and placebo groups, will constitute secondary endpoints.
Also, the difference between rituximab and placebo groups, in changes from baseline to recording at 18 months, for Physical health summary score, Physical function, and "mean of five SF-36 subdimensions", constitute secondary endpoints. |
Changes in SF-36 scores during 24 months follow-up | |
| Secondary | Physical activity (Sensewear armband) | The patients' physical activity level, in a home setting for 7 consecutive days, is recorded using Sensewear armbands, with registration at baseline and repeated in the time interval 17-21 months follow-up. Changes from baseline to analysis during the time interval 17-21 months, for mean number of steps per 24h, maximum number of steps per 24h, mean duration per 24h with activity level at least 3.5 METs, max duration per 24h with activity level at least 3.5 METs, are recorded. The difference between rituximab and placebo groups will constitute secondary endpoints. | Analyzed at baseline and at interval 17-21 months | |
| Secondary | Self-recorded "Function level" | Self-recorded "Function level" (scale 0-100, compared to healthy state, according to a set of examples) are registered every second week. Mean "Function level" for the time intervals 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 months are calculated. The difference in course of "Function level", between the rituximab and placebo groups, constitute a secondary endpoint.
Also, the differences between the rituximab and placebo groups, for changes in selfreported "Fatigue score" and in selfreported "Function level", calculated from baseline to the mean value during the time interval 16-20 months, constitute secondary endpoints. |
Course during 24 months follow-up | |
| Secondary | Fatigue Severity Scale | Fatigue Severity Scale (FSS) is self-recorded at baseline and at 6, 12, 18, 24 months. The difference between the rituximab and placebo groups, in changes in FSS from baseline to 18 months follow-up, constitutes a secondary endpoint. | 24 months | |
| Secondary | Clinical response duration | Clinical response periods, defined as consecutive self-recorded Fatigue score at least 4.5 (scale 0-6) for a minimum of 8 weeks, during 24 months follow-up, are recorded.
The difference in the longest consecutive clinical response period, between rituximab and placebo groups, constitutes a secondary endpoint. |
During 24 months follow-up | |
| Secondary | Sustained clinical response at 24 months | The difference between rituximab and placebo groups, in fraction of patients with sustained clinical response (defined as Fatigue score of at least 4.5) at 24 months, constitute a secondary endpoint. | Assessment at 24 months |