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.
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.
复制标题
精神病免疫机制分层药物（PIMS）试验的方案：一项在精神病患者中单剂量tocilizumab的随机双盲安慰剂对照试验。
DOI：
10.1136/bmjopen-2022-067944
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发表时间：
2023-03-24
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
有证据表明，白细胞介素6（IL-6），一种通常促进炎症的多效性细胞因子，在精神病的发病机制中具有潜在的因果作用。然而，尚未在精神病患者中进行使用炎症标志物分层的干预性研究，以评估靶向IL-6在精神病中的治疗潜力并阐明潜在的作用机制。Tocilizumab是一种靶向IL-6受体的人源化单克隆抗体，可抑制IL-6信号传导，在英国获得许可用于治疗类风湿性关节炎。本研究的主要目的是测试IL-6是否有助于首发精神病的发病机制，并检查IL-6影响精神病症状的潜在机制。次要目的是检查炎症相关精神病的特征。一项采用随机、平行组、双盲、安慰剂对照设计的概念验证研究，旨在检测IL-6抑制对精神病患者快感缺失的影响。约60例诊断为精神分裂症和相关精神障碍（ICD-10代码F20、F22、F25、F28、F29）并有轻度炎症证据（IL-6≥0.7 pg/mL）的受试者将接受一次托珠单抗（4.0 mg/kg;最大800 mg）或生理盐水静脉输注。将在基线、输注后7、14和28天采集精神病学指标和血液样本。将在基线和输注后14天收集认知和神经影像学数据。此外，将招募约30名无炎症证据的精神病患者（IL-6<0.7 pg/mL）和30名匹配的健康对照，以完成相同的基线评估，从而比较炎症相关精神病的特征。本研究由布里斯托大学申办，并已获得剑桥东部研究伦理委员会的批准（参考编号：22/EE/0010; IRAS项目ID：301682）。研究结果将发表在同行评审期刊上。还将通过科学介绍和其他方式传播调查结果。 ISRCTN23256704。
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. 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≥0.7 pg/mL) will receive either one intravenous infusion of tocilizumab (4.0 mg/kg; max 800 mg) 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<0.7 pg/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. 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. ISRCTN23256704.
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DOI：
10.1016/j.bbih.2021.100330
发表时间：
2021-11
期刊：
Brain, behavior, & immunity - health
影响因子：
--
作者：
Corsi-Zuelli F;Deakin B;de Lima MHF;Qureshi O;Barnes NM;Upthegrove R;Louzada-Junior P;Del-Ben CM
通讯作者：
Del-Ben CM
DOI：
10.1016/j.bbi.2017.11.020
发表时间：
2018-03
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Khandaker GM;Zammit S;Burgess S;Lewis G;Jones PB
通讯作者：
Jones PB
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
4.5
作者：
Khandaker, Golam M.;Zimbron, Jorge;Dalman, Christina;Lewis, Glyn;Jones, Peter B.
通讯作者：
Jones, Peter B.
影响因子：
3.4
作者：
Khandaker GM;Dantzer R
通讯作者：
Dantzer R