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

Summary

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.

Timeline

Start

2022-05-01

Primary completion

2028-04-01

Completion

2028-12-01

Publications

• Background Debnath M, Venkatasubramanian G. Recent advances in psychoneuroimmunology relevant to schizophrenia therapeutics. Curr Opin Psychiatry. 2013 Sep;26(5):433-9. doi: 10.1097/YCO.0b013e328363b4da.
• Background Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, Xu C, Richter MA, Kahn A, Kish SJ, Houle S, Ravindran L, Meyer JH. Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder. JAMA Psychiatry. 2017 Aug 1;74(8):833-840. doi: 10.1001/jamapsychiatry.2017.1567.
• Background Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D. Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology. 2012 Aug;37(9):2076-87. doi: 10.1038/npp.2012.56. Epub 2012 Apr 25.
• Background Lee WJ, Lee ST, Byun JI, Sunwoo JS, Kim TJ, Lim JA, Moon J, Lee HS, Shin YW, Lee KJ, Kim S, Jung KH, Jung KY, Chu K, Lee SK. Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort. Neurology. 2016 May 3;86(18):1683-91. doi: 10.1212/WNL.0000000000002635. Epub 2016 Apr 1.
• Background Dazzi F, Shafer A, Lauriola M. Meta-analysis of the Brief Psychiatric Rating Scale - Expanded (BPRS-E) structure and arguments for a new version. J Psychiatr Res. 2016 Oct;81:140-51. doi: 10.1016/j.jpsychires.2016.07.001. Epub 2016 Jul 4.

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Indications