Rituximab tested in psychosis or obsessive compulsive disorder with immune involvement

Trial details

Who runs it

Uppsala University Hospital

Trial code

NCT04323566EU 2024-518391-31-00

Record updated

19 November 2024

Original description

The primary objective for this study is to evaluate whether Rituximab as compared to placebo is a clinically effective treatment for a subgroup of patients suffering from psychosis and/or obsessive-compulsive disorder (OCD) or -behavior (OCB) where there is an indication of immune system involvement.Read full original descriptionShow less

A Randomized, Double-blinded, Placebo-controlled Study of Rituximab in Patients with Psychosis And/or Obsessive Compulsive Disorder, with an Indication of Immune System Involvement

The primary objective for this study is to evaluate whether Rituximab as compared to placebo is a clinically effective treatment for a subgroup of patients suffering from psychosis and/or obsessive-compulsive disorder (OCD) or -behavior (OCB) where there is an indication of immune system involvement.

The secondary objectives of this study are

1. To assess whether Rituximab treatment (with the doses and timing described below) as compared to placebo is associated with amelioration in psychiatric symptomatology 2. To assess whether Rituximab treatment as compared to placebo is associated with improvement in executive functions 3. To assess whether Rituximab treatment as compared to placebo is associated with amelioration in neurological symptoms 4. To evaluate the longevity of psychiatric, neurological and executive improvements associated with Rituximab treatment for up to 16 months after the first infusion (i.e. 12 months after the last infusion) 5. To evaluate whether Rituximab treatment as described is safe for these patients.

The exploratory objectives of this study are

1. To assess changes in blood and cerebrospinal fluid (CSF) markers for immune activity associated with Rituximab treatment compared to placebo 2. To assess statistical associations between biological markers in blood or CSF and clinical response 3. To describe changes in somatic symptoms associated with treatment with Rituximab vs placebo for patients with initial symptoms in the questionnaires 4. To describe changes on MR and EEG associated with treatment with Rituximab vs placebo for patients with initial pathology in these examination 5. To study immune mechanisms coupled with psychiatric symptoms, possibly identifying novel biomarkers with potential for subtyping encephalopathies with immune engagement, using biobank cells, blood and CSF samples collected from the participants.

Inclusion: 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: 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; Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency; Current drug, alcohol, or chemical abuse; Concomitant malignancies or previous malignancies within the last five years; History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever); 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); History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study; 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; Cannot comply with vaccination recommendations; Pregnancy at any time during the study; Patient is enrolled in another medical trial.

ClinicalTrials.gov NCT04323566 · EU CTIS 2024-518391-31-00