TY - JOUR
T1 - Protocol for the insight study
T2 - a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation
AU - Khandaker, Golam M
AU - Oltean, Bianca P
AU - Kaser, Muzaffer
AU - Dibben, Claire R M
AU - Ramana, Rajini
AU - Jadon, Deepak R
AU - Dantzer, Robert
AU - Coles, Alasdair J
AU - Lewis, Glyn
AU - Jones, Peter B
N1 - © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.
PY - 2018/9/21
Y1 - 2018/9/21
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal, Humanized/administration & dosage
KW - Biomarkers/blood
KW - C-Reactive Protein/metabolism
KW - Cognition/drug effects
KW - Depressive Disorder/drug therapy
KW - Double-Blind Method
KW - Humans
KW - Inflammation/complications
KW - Infusions, Intravenous
KW - Proof of Concept Study
KW - Psychiatric Status Rating Scales
KW - Randomized Controlled Trials as Topic
KW - Receptors, Interleukin-6/antagonists & inhibitors
KW - Treatment Outcome
U2 - 10.1136/bmjopen-2018-025333
DO - 10.1136/bmjopen-2018-025333
M3 - Article (Academic Journal)
C2 - 30244217
VL - 8
SP - e025333
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 9
ER -