Rituximab Treatment for Psychosis And/or Obsessive Compulsive Disorder with Probable Immune System Involvement

Launched by UPPSALA UNIVERSITY HOSPITAL · Mar 24, 2020

Keywords

ClinConnect Summary

METHODOLOGY:

This study is planned as a placebo-controlled, interventional study of parallel groups with 40 participants. Patients will be randomized to either treatment-first arm with 500 mg Rituximab i.v. (infusion 1) at 0 and again at 4 months (infusion 2), or placebo-first arm, receiving NaCl-infusion at 0 and at 4 months. Main evaluation will take place at eight months. The study arms are switched after eight months, i.e. patients starting in the treatment-first arm will receive placebo (NaCl) infusions at 8 months (infusion 3) and 12 months (infusion 4), and patients in the placebo-f...

Gender

ALL

Eligibility criteria

• • INCLUSION CRITERIA
• • General criteria
• 1. Diagnostic criteria: ICD 10 at least one of the following ICD 10 diagnoses:
• • 1. Obsessive-compulsive disorder ICD F42 or
• • 2. Obsessive-compulsive behavior ICD R46.81 AND/OR
• • 3. 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
• • 2. Age: 18-55
• • 3. Severity: Clinical Global impression (CGI): Minimum score of "4 = Moderately ill"
• • 4. Swedish or English proficiency
• • 5. 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
• • 6. Medication has been unchanged for at least one month prior to study start
• • 7. Signed informed consent
• • 8. Use of adequate contraception
• • 9. Radiological evidence of brain atrophy and scarring are absent
• • 10. 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
• 11. Acute (\<12 weeks) or atypical debut, or episodes of any of the following:
• 1. 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
• • 2. Focal neurological symptoms, e.g. ataxia, dystonia, myoclonus, sensory losses, paresthesia
• • 3. Psychomotor anomaly, e.g.retardation, catatonic symptoms, parkinsonism
• • 4. Loss of drive (sleep, appetite, libido, motivation)
• • 5. Obsessions, compulsions (OCD/OCB),
• • 6. Hypo- or hypervigilance (for e.g sounds, emotions, other peoples´ or own behavior)
• • 7. Sleeping disorders,
• • AND
• 12. At least one of the following criteria:
• • 1. Prodromal phase with infection or symptoms of infection (fever, malaise, etc)
• • 2. Clinical improvement of psychiatric symptoms after treatment with anti-inflammatory medications other than antibody therapy (such as steroids, NSAIDs IVIG, plasmaphereses), or antibiotics
• • 3. Radiological evidence of neuroinflammation (MR)
• • 4. EEG pathology or witnessed epileptic seizure
• 5. 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
• • 6. 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
• • 7. 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
• • 13. Concomitant malignancies or previous malignancies within the last five years
• • 14. Cannot comply with vaccination recommendations
• • 15. History of severe allergic or anaphylactic reactions in conjunction with prior treatment with monoclonal antibodies
• • 16. Prior antibody therapy including Rituximab (MabThera®/Rituxan®)
• • 17. Patient has been treated with clozapine (which may have immunosuppressant effect), systemic corticosteroids or IVIG within 60 days prior to screening visit
• • 18. Prior treatment with immunosuppressant medications (not including systemic corticosteroids and IVIG) for other medical condition
• • 19. History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever)
• • 20. Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency
• • 21. Current drug, alcohol, or chemical abuse
• • 22. Pregnancy at any time during the study
• • 23. Known chronical significant bacterial/viral/fungal infections at infusion date
• • 24. Diagnosis of well-established neuroinflammatory disease such as Multiple Sclerosis (MS) (ICD codes G00-G09, G35-G37) or systemic lupus erythematosus (SLE) (M32)
• • 25. 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.
• • 26. History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study.
• • 27. Patient is enrolled in another medical trial.