Rituximab for Psychosis | Obsessive-compulsive disorder

Inclusion criteria

• {"criterion_text":"- Patients to be included in this study meet the criteria for at least one of the following ICD 10 CM diagnoses: o\tObsessive-compulsive disorder ICD F42 or o\tObsessive-compulsive behavior ICD R46.81 o\tSchizophrenia, delusional, and other non-mood psychotic disorders, namely \tF20 Schizophrenia \tF22 Delusional disorders \tF23 Brief psychotic disorder \tF25 Schizoaffective disorders \tF28 Other psychotic disorder not due to a substance or known physiological condition \tF29 Unspecified psychosis not due to a substance or known physiological condition"}
• {"criterion_text":"- The clinical picture indicates active inflammatory activity (see specific criteria below), potential for rehabilitation and time from disease and/or episode debut is no longer than 10 years."}
• {"criterion_text":"- Acute (<12 weeks) or atypical debut, or episodes of any of the following: a.\tSymptoms of encephalopathy: \tpsychotic symptoms, including hallucinations, delusions, paranoia, disorganized speech, disorganized behavior \tagitation, confusion \tsudden change in personality as perceived by the social environment \tdrowsiness \tloss of functions in daily life \tcognitive problems (memory, speech, learning) \temotional dysregulation b.\tFocal neurological symptoms, e.g. \tataxia, dystonia, myoclonus, sensory losses, paresthesia c.\tPsychomotor anomaly, \te.g. retardation, catatonic symptoms, parkinsonism d.\tLoss of drive (sleep, appetite, libido, motivation) e.\tObsessions, compulsions (OCD/OCB), f.\tHypo- or hypervigilance (for e.g sounds, emotions, other peoples´ or own behavior) g.\tSleeping disorders, AND"}
• {"criterion_text":"- AND\tAt least one of the following criteria: a.\tProdromal phase with infection or symptoms of infection (fever, malaise, etc) b.\tClinical improvement of psychiatric symptoms after treatment with anti-inflammatory medications other than antibody therapy (such as steroids, NSAIDs IVIG, plasmaphereses), or antibiotics c.\tRadiological evidence of neuroinflammation (MR) d.\tEEG pathology or witnessed epileptic seizure e.\tBiochemical evidence of inflammation, autoimmunity or blood-brain barrier dysfunction in blood or CSF samples, such as one of the following: \tpresence of oligoclonal bands \televated CSF cell count \televated albumin quotient, or elevated albumin in CSF \televated IgG ratio \televated levels of neurofilament f.\tPatient history of autoimmune disorder not associated with neuroinflammation, such as type 1 diabetes, rheumatoid arthritis, Sjögren´s syndrome, inflammatory bowel disease (IBD, comprising Crohn´s disease and ulcerative colitis), celiac disease, Grave´s disease, Hashimoto`s thyroiditis g.\tBiochemical indication of autoimmunity such as elevated serum anti-TPO, ANA, ANCA, RF or GAD antibodies, PANDAS panel with relationship to symptom development."}
• {"criterion_text":"- Age: 18-55"}
• {"criterion_text":"- Severity: Clinical Global impression (CGI): Minimum score of “4 = Moderately ill”"}
• {"criterion_text":"- Swedish or English proficiency"}
• {"criterion_text":"- The patient has tried at least 2 standard psychiatric medications at maximal tolerable or maximal recommended dosage for his/her current condition over a period of 6 months, but has not improved significantly"}
• {"criterion_text":"- Medication has been unchanged for at least one month prior to study start"}
• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Use of adequate contraception"}
• {"criterion_text":"- Radiological evidence of brain atrophy and scarring are absent"}

Exclusion criteria

• {"criterion_text":"- Concomitant malignancies or previous malignancies within the last five years"}
• {"criterion_text":"- Pregnancy at any time during the study"}
• {"criterion_text":"- Known chronical significant bacterial/viral/fungal infections"}
• {"criterion_text":"- Diagnosis of well-established neuroinflammatory disease such as MS (ICD codes G00–G09, G35–G37) or SLE (M32)"}
• {"criterion_text":"- Tested positive for autoantibodies in serum or CSF associated to known and treatable neuroinflammatory disease (such as neuroborreliosis, treatable autoimmune encephalitis). Patients having completed recommended treatment without significant improvement may still be included in this study."}
• {"criterion_text":"- History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study."}
• {"criterion_text":"- Patient is enrolled in another medical trial."}
• {"criterion_text":"- Cannot comply with vaccination recommendations"}
• {"criterion_text":"- History of severe allergic or anaphylactic reactions in conjunction with prior treatment with monoclonal antibodies"}
• {"criterion_text":"- Prior antibody therapy including Rituximab (MabThera®/Rituxan®)"}
• {"criterion_text":"- Patient has been treated with clozapine (which may have immunosuppressant effect), systemic corticosteroids or IVIG within 60 days prior to screening visit"}
• {"criterion_text":"- Prior treatment with immunosuppressant medications (not including systemic corticosteroids and IVIG) for other medical condition"}
• {"criterion_text":"- History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever)"}
• {"criterion_text":"- Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency"}
• {"criterion_text":"- Current drug, alcohol, or chemical abuse"}

Primary endpoints

• {"endpoint_text":"- The clinical efficacy of Rituximab treatment will be evaluated by calculating the average difference between BPRS scores at baseline and main-evaluation (8-month) and comparing it between the treatment-first and the placebo-first group.","definition_or_measurement_approach":"Calculate the average difference between BPRS scores at baseline and main-evaluation (8-month) and compare between treatment-first and placebo-first groups (BPRS score change at 8 months)."}

Secondary endpoints

• {"endpoint_text":"- 1.\tThe amelioration in psychiatric symptomatology will be assessed by following the psychiatric rating scales: o\tCGI o\tWHODAS, o\tEQ-VAS, o\tY-BOCS o\tBFCS","definition_or_measurement_approach":"Assessment by psychiatric rating scales: CGI, WHODAS, EQ-VAS, Y-BOCS, BFCS as listed."}
• {"endpoint_text":"- 2.\tImprovement in executive functions, will be assessed by following neuropsychiatric tests: o\tNeuropsychological tests o\tMismatch negativity","definition_or_measurement_approach":"Assessment by neuropsychological tests and mismatch negativity measurements as listed."}
• {"endpoint_text":"- 3.\tThe amelioration of neurological symptoms will be assessed by performing complete, video-recorded neurological exams. This procedure is described in section 11.","definition_or_measurement_approach":"Assessment via complete, video-recorded neurological examinations (per protocol section 11)."}
• {"endpoint_text":"- 4.\tThe longevity of psychiatric, neurological and executive improvements will be examined by the psychiatric ratings scales named in 1. and blood samples every 4 months up to 16 months, and in addition to that a thorough neurological exam, the executive tests named in 2. and CSF samples every 8 months up to 16 months.","definition_or_measurement_approach":"Longitudinal assessment using the psychiatric rating scales every 4 months (blood samples every 4 months) up to 16 months; neurological exams and executive tests plus CSF samples every 8 months up to 16 months."}
• {"endpoint_text":"- 5.\tThe safety of Rituximab treatment will be assessed by adverse events monitoring and questionnaires described in detail in section 12.","definition_or_measurement_approach":"Safety assessed by adverse events monitoring and study questionnaires (per protocol section 12)."}

Sweden

Earliest CTIS Part Ii Submission Date

26-09-2024

Latest Decision Or Authorization Date

05-11-2024

Processing Time Days

40

Number Of Sites

1

Number Of Participants

40

Primary sponsor

Full Name

Region Uppsala

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden