myalgia encephalomyelitis/chronic fatigue syndrome
Conditions
Interventions
Subjects will be assigned to the rituximab pre-treatment group or placebo pre-treatment group and will receive the study drug (rituximab actual or rituximab placebo) intravenously four times at weekly
Sponsors
Okamoto Tomoko
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Patients diagnosed with ME/CFS who meet the Canadian criteri by a physician. (2) Patients with a severity score of 4 or higher on the Performance Status (PS) based ME/CFS severity classification by the Ministry of Health, Labour and Welfare Research Group (3) Patients who are between 18 and 65 years of age at the time of obtaining written consent (4) Patients who can be hospitalized (hospitalized from the day before administration and discharged the day after administration) at the time of the first dose of each of the primary and secondary evaluation periods (5) Patients whose written consent has been obtained
Exclusion criteria
Exclusion criteria: (1) Patients with a history of severe hypersensitivity or anaphylactic reactions to components of rituximab or products derived from mouse protein (2) Patients whose cardiopulmonary function is judged by the treating physician to be not maintained (3) Patients complaining of fatigue that does not meet the diagnostic criteria for ME/CFS (4) Patients found to have other medical conditions that may cause symptoms (5) Patients who are pregnant, lactating, or have a positive pregnancy test (serum human chorionic gonadotropin test) at the time of enrollment (6) Patients with coexisting or pre-existing malignant tumors (excluding basal cell carcinoma of the skin and cervical dysplasia) (7) Patients with coexisting or pre-existing severe immune system diseases (excluding autoimmune diseases such as thyroiditis and type 1 diabetes) (8) Patients with a history of systemic immunosuppressive therapy (e.g., immunoglobulin therapy, azathioprine, cyclosporine, mycophenolate mofetil, etc.) within 1 year, a history of receiving drugs such as monoclonal antibodies acting on the immune system (e.g., anti-CD20 antibody products including rituximab), or a history of comorbidities requiring treatment with immunosuppressive drugs Patients with comorbidities requiring treatment with immunosuppressive agents (excluding treatment with low-dose steroids of 5 mg /day or less) (9) Patients who have started alternative medicine (reference: acupuncture, moxibustion, and Japanese warm therapy) within 12 weeks prior to the start of treatment with the investigational drug. (10) Patients with severe endogenous (primary) depression (11) Patients with a neutrophil count 1.5 times the upper limit of the reference value at the institution) (13) Patients with impaired hepatic function (serum bilirubin, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) levels exceeding 1.5 times the upper limit of the reference value of the institution) (14) Patients infected with Human Immunodeficiency Virus (HIV) (15) Patients who test positive for at least one of Hepatitis B surface (HBs) antigen, HBs antibody, Hepatitis B core (HBc) antibody, or Hepatitis C virus (HCV) antibody. However, patients who meet the following conditions (1) and (2) may be registered. (i) Patients who are positive for HBs or HBc antibodies and whose HBV-DNA quantification is confirmed to be negative (less than detection sensitivity) and for whom appropriate monitoring, etc. can be conducted in accordance with the Guidelines for Hepatitis B Treatment edited by the Japan Society of Hepatology. (ii) For patients with positive HCV antibody, when HCV-RNA quantification is negative (less than detection sensitivity) (16) Patients who do not have the ability to comply with the study protocol (17) Patients who have participated in other clinical trials or clinical studies (except for observational studies without intervention) within 16 weeks prior to obtaining consent (18) Other patients who are judged by the investigator or subinvestigator (hereinafter referred to as investigator) to be inappropriate to participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of cases in which the severity score of ME/CFS based on PS by the MHLW research group improved by 1 or more compared to that before the start of study drug administration (week 0) (improvement rate) | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy (1) Percentage of patients whose MHLW-PS-based ME/CFS severity score improved by 1 or more at each evaluation point (improvement rate) compared to that before the start of treatment with the investigational drug (week 0). (2) The amount of change in the severity score of ME/CFS based on PS by the MHLW Research Group at each assessment point from that before the start of treatment with the investigational drug (week 0) (3) Proportion of awake time spent in supine position (%) (4) Proportion of awake time spent in sitting position (%) (5) Duration of standing and activity (hours) (6) Fatigue during rest and lying position (7) Records on exertion, Post-Exertional Malaise (PEM) (8) Fatigue during exercise (evaluation based on Modified Borg scale) (9) Evaluation based on Fatigue Score (10) Change in symptom scores (quality of life (QOL), autonomic nervous system, sleep, pain, etc.) at each assessment point from before the start of study drug administration (week 0) (11) Grip strength (12) Gut microbiota analysis (13) Brain imaging evaluation (Magnetic Resonance Imaging (MRI) of the head, Single Photon Emission Computed Tomography (SPECT) of cerebral blood flow) (14) Immune biomarker analysis (B cell receptor leptore analysis, T cell receptor leptore analysis, qPCR analysis, anti-autonomic receptor antibody analysis, immune cell subfractionation analysis) (15) Metabolome analysis Safety (1) Adverse events (2) Laboratory tests (hematology, blood biochemistry, urinalysis) (3) Vital signs (temperature, pulse rate, blood pressure) (4) Serum immunoglobulins (IgG, IgM, IgA) Other items (1) Blood drug concentration (2) Anti-Drug Antibody (ADA) (3) B cells (CD19/CD20 positive cells) and T cells (CD3/CD4/CD8 positive cells) | — |
Contacts
Public ContactTakami Ishizuka
National Center Hospital, National Center of Neurology and Psychiatry
Outcome results
None listed