Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis

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Foley, Eimear M. ; Griffiths, Sian Lowri ; Murray, Alexander ; Rogers, Jack ; Corsi-Zuelli, Fabiana ; Hickinbotham, Hannah ; Warwick, Ella ; Wilson, Martin ; Kaser, Muzaffer ; Murray, Graham K. ; Deakin, Bill ; Jadon, Deepak ; Suckling, John ; Barnes, Nicholas M. ; Upthegrove, Rachel ; Khandaker, Golam M. ; PIMS Collaboration

• Tipo de documento: Artigo Científico
• Fonte: BMJ OPEN; v. 13, n. 3, p. 10-pg., 2023-02-01.

Resumo

Introduction Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. However, no interventional studies in patients with psychosis, stratified using inflammatory markers, have been conducted to assess the therapeutic potential of targeting IL-6 in psychosis and to elucidate potential mechanism of effect. Tocilizumab is a humanised monoclonal antibody targeting the IL-6 receptor to inhibit IL-6 signalling, licensed in the UK for treatment of rheumatoid arthritis. The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. A secondary objective is to examine characteristics of inflammation-associated psychosis. Methods and analysis A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of IL-6 inhibition on anhedonia in patients with psychosis. Approximately 60 participants with a diagnosis of schizophrenia and related psychotic disorders (ICD-10 codes F20, F22, F25, F28, F29) with evidence of low-grade inflammation (IL-6 >= 0.7pg/mL) will receive either one intravenous infusion of tocilizumab (4.0 mg/kg; max 800mg) or normal saline. Psychiatric measures and blood samples will be collected at baseline, 7, 14 and 28 days post infusion. Cognitive and neuroimaging data will be collected at baseline and 14 days post infusion. In addition, approximately 30 patients with psychosis without evidence of inflammation (IL-6<0.7pg/mL) and 30 matched healthy controls will be recruited to complete identical baseline assessments to allow for comparison of the characteristic features of inflammation-associated psychosis. Ethics and dissemination The study is sponsored by the University of Bristol and has been approved by the Cambridge East Research Ethics Committee (reference: 22/EE/0010; IRAS project ID: 301682). Study findings will be published in peer-review journals. Findings will also be disseminated by scientific presentation and other means. (AU)

• Processo FAPESP: 19/13229-2 - Perfil inflamatório na população geral: evidência dimensional transdiagnóstica no contexto do continuum das psicoses
• Beneficiário: Fabiana Maria das Graças Corsi Zuelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/07448-3 - Imunofenotipagem de pacientes com psicose imunologicamente ativos e o papel da interleucina-6
• Beneficiário: Fabiana Maria das Graças Corsi Zuelli
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado