Rituximab Treatment for Psychosis and/or Obsessive Compulsive Disorder With Probable Immune System Involvement (Ra-P-OCD)
Obsessive-Compulsive Disorder, Obsessive-Compulsive Behavior, Schizophrenia
About this trial
This is an interventional treatment trial for Obsessive-Compulsive Disorder
Eligibility Criteria
INCLUSION CRITERIA
General criteria
Diagnostic criteria: ICD 10 at least one of the following ICD 10 diagnoses:
- Obsessive-compulsive disorder ICD F42 or
- Obsessive-compulsive behavior ICD R46.81 AND/OR
- Schizophrenia, delusional, and other non-mood psychotic disorders, namely
F20 Schizophrenia
F22 Delusional disorders
F23 Brief psychotic disorder
F25 Schizoaffective disorders
F28 Other psychotic disorder not due to a substance or known physiological condition
F29 Unspecified psychosis not due to a substance or known physiological condition
- Age: 18-55
- Severity: Clinical Global impression (CGI): Minimum score of "4 = Moderately ill"
- Swedish or English proficiency
- 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
- Medication has been unchanged for at least one month prior to study start
- Signed informed consent
- Use of adequate contraception
- Radiological evidence of brain atrophy and scarring are absent
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.
Specific criteria
Acute (<12 weeks) or atypical debut, or episodes of any of the following:
Symptoms of encephalopathy:
psychotic symptoms, including hallucinations, delusions, paranoia, disorganized speech, disorganized behavior
agitation, confusion
sudden change in personality as perceived by the social environment
drowsiness
loss of functions in daily Life
cognitive problems (memory, speech, learning)
emotional dysregulation
- Focal neurological symptoms, e.g. ataxia, dystonia, myoclonus, sensory losses, paresthesia
- Psychomotor anomaly, e.g.retardation, catatonic symptoms, parkinsonism
- Loss of drive (sleep, appetite, libido, motivation)
- Obsessions, compulsions (OCD/OCB),
- Hypo- or hypervigilance (for e.g sounds, emotions, other peoples´ or own behavior)
- Sleeping disorders,
AND
At least one of the following criteria:
- Prodromal phase with infection or symptoms of infection (fever, malaise, etc)
- Clinical improvement of psychiatric symptoms after treatment with anti-inflammatory medications other than antibody therapy (such as steroids, NSAIDs IVIG, plasmaphereses), or antibiotics
- Radiological evidence of neuroinflammation (MR)
- EEG pathology or witnessed epileptic seizure
Biochemical evidence of inflammation, autoimmunity or blood-brain barrier dysfunction in blood or CSF samples, such as one of the following:
presence of oligoclonal bands
elevated CSF cell count
elevated albumin quotient, or elevated albumin in CSF
elevated Immunoglobulin G (IgG) ratio
elevated levels of neurofilament
- Patient 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
- Biochemical indication of autoimmunity such as elevated serum anti-thyroid peroxidase (TPO) antibody, antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), rheumatoid factor (RF) or glutamic acid decarboxylase (GAD) antibodies, PANDAS panel with relationship to symptom development.
EXCLUSION CRITERIA
- Concomitant malignancies or previous malignancies within the last five years
- Cannot comply with vaccination recommendations
- History of severe allergic or anaphylactic reactions in conjunction with prior treatment with monoclonal antibodies
- Prior antibody therapy including Rituximab (MabThera®/Rituxan®)
- Patient has been treated with clozapine (which may have immunosuppressant effect), systemic corticosteroids or IVIG within 60 days prior to screening visit
- Prior treatment with immunosuppressant medications (not including systemic corticosteroids and IVIG) for other medical condition
- History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever)
- Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency
- Current drug, alcohol, or chemical abuse
- Pregnancy at any time during the study
- Known chronical significant bacterial/viral/fungal infections at infusion date
- Diagnosis of well-established neuroinflammatory disease such as Multiple Sclerosis (MS) (ICD codes G00-G09, G35-G37) or systemic lupus erythematosus (SLE) (M32)
- 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.
- History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study.
- Patient is enrolled in another medical trial.
Sites / Locations
- Uppsala University Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Treatment-first arm
Placebo-first arm
Participants receive i.v. infusions with 500 mg Rituximab at 0 and 4 months, followed by placebo infusions (NaCl) at 8 and at 12 months, Pre-treatment prior to all four infusions consists of injection Solu-Medrol 125 mg i.v., tablet Paracetamol 1000 mg p.o. and tablet Cetirizin 10 mg p.o.
Participants receive placebo (NaCl) i.v. infusions at 0 and 4 months, followed by 500-mg-Rituximab infusions at 8 and 12 months. Pre-treatment prior to all four infusions consists of injection Solu-Medrol 125 mg i.v., tablet Paracetamol 1000 mg p.o. and tablet Cetirizin 10 mg p.o.