Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)

BMC Psychiatry

Study Protocol

Predrag Petrovic¹  Alexander Lebedev¹  Scott Montgomery²  Max Albert Hietala³  Per Thunberg⁴  Annika Söderbergh⁵  Susanne Bejerot⁶  Axel Nordenskjöld⁷  Mats B. Humble⁷  Daniel Eklund⁷  Niclas Lange⁷  Sverre Wikström⁸  Tarmo Kariis⁹  Hugo Hesser^1,10 

[1] Center for Psychiatry Research (CPF), Center for Cognitive and Computational Neuropsychiatry (CCNP), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;Department of Neurology, Karolinska University Hospital, Stockholm, Sweden;Department of Radiology and Medical Physics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;Center for Experimental and Biomedical Imaging in Örebro (CEBIO), Faculty of Medicine and Health, Örebro University, Örebro, Sweden;Department of Rheumatology, Örebro University Hospital, Örebro, Sweden;Faculty of Health and Medical Sciences, University Health Care Research Centre, Örebro University, Örebro, Sweden;Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden;Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden;Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden;Karlstad Central Hospital, Region Värmland, Karlstad, Sweden;School of Behavioural, Social and Legal Sciences, Örebro University, Örebro, Sweden;

关键词: Clinical trials;    Inflammation;    Monoclonal antibodies;    Immunology;    Magnetic resonance imaging;    Schizophrenia & psychotic disorders;   

DOI  :  10.1186/s12888-023-05250-5

 received in 2023-09-22, accepted in 2023-10-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance.The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.MethodsA proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.DiscussionThis is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.Trial registrationNCT05622201, EudraCT-nr 2022–000220-37 version 2.1. registered 14th of October 2022.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 1