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

This study is testing whether Rituximab, a medicine that targets parts of the immune system, might help people with psychosis and obsessive-compulsive symptoms when doctors think immune factors in the brain could be involved. About 40 adults, ages 18–55, with diagnoses like OCD, obsessive-compulsive behavior, schizophrenia, or related psychotic disorders are being considered. To join, you would need to have tried at least two standard psychiatric medicines at full dose for about six months without enough improvement, and your condition should be stable enough to participate. You must not have had Rituximab before, and you should not have serious infections or other conditions that would make treatment unsafe. The trial is at Uppsala University Hospital in Sweden and is designed so that neither you nor your care team knows who gets the real drug or placebo during the first part of the study.

Participants are randomly assigned to start with Rituximab or placebo, given as intravenous infusions at 0 and 4 months (500 mg Rituximab or saline). After eight months, the two groups switch so everyone has a chance to receive both the real drug and the placebo. Before each infusion you get medication to prevent reactions. Over 16 months you’ll have regular psychiatric assessments, tests of daily functioning, and blood tests; at baseline, eight months, and sixteen months you’ll also have a lumbar puncture (to collect cerebrospinal fluid) and some brain function tests. The main goal is to see if Rituximab improves overall psychiatric symptoms at eight months, with additional safety and functioning measures, plus several exploratory biological tests. If you’re considering participation, talk with the study team about eligibility, what to expect, and any potential risks. The study is running under a double-blind design at Uppsala University Hospital, and results are not yet available.

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.