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Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.

Published version
Peer-reviewed

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Authors

Oltean, Bianca P 
Kaser, Muzaffer 
Dibben, Claire RM 
Ramana, Rajini 

Abstract

INTRODUCTION: Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sensitivity C reactive protein (hs-CRP) level ≥3 mg/L, will receive either a single intravenous infusion of tocilizumab or normal saline. Blood samples, behavioural and cognitive measures will be collected at baseline and after infusion around day 7, 14 and 28. The primary outcome is somatic symptoms score around day 14 postinfusion. In addition, approximately, 50 depressed participants without low-grade inflammation (serum hs-CRP level <3 mg/L) will complete the same baseline assessments as the randomised cohort. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee (REC) (Reference: 18/SC/0118). Study findings will be published in peer-review journals. Findings will be also disseminated by conference/departmental presentations and by social and traditional media. TRIAL REGISTRATION NUMBER: ISRCTN16942542; Pre-results.

Description

Keywords

clinical trials, Antibodies, Monoclonal, Humanized, Biomarkers, C-Reactive Protein, Cognition, Depressive Disorder, Double-Blind Method, Humans, Inflammation, Infusions, Intravenous, Proof of Concept Study, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, Receptors, Interleukin-6, Treatment Outcome

Journal Title

BMJ Open

Conference Name

Journal ISSN

2044-6055
2044-6055

Volume Title

8

Publisher

BMJ
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
Wellcome Trust (201486/Z/16/Z)
Medical Research Council (MR/N019067/1)