Show simple item record

dc.contributor.authorKhandaker, Golam M
dc.contributor.authorOltean, Bianca P
dc.contributor.authorKaser, Muzaffer
dc.contributor.authorDibben, Claire RM
dc.contributor.authorRamana, Rajini
dc.contributor.authorJadon, Deepak R
dc.contributor.authorDantzer, Robert
dc.contributor.authorColes, Alasdair J
dc.contributor.authorLewis, Glyn
dc.contributor.authorJones, Peter B
dc.date.accessioned2018-10-03T04:45:14Z
dc.date.available2018-10-03T04:45:14Z
dc.date.issued2018-09-21
dc.identifier.issn2044-6055
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283086
dc.description.abstractINTRODUCTION: 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.
dc.format.mediumElectronic
dc.languageeng
dc.publisherBMJ
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectInflammation
dc.subjectC-Reactive Protein
dc.subjectReceptors, Interleukin-6
dc.subjectTreatment Outcome
dc.subjectInfusions, Intravenous
dc.subjectDouble-Blind Method
dc.subjectCognition
dc.subjectDepressive Disorder
dc.subjectPsychiatric Status Rating Scales
dc.subjectRandomized Controlled Trials as Topic
dc.subjectAntibodies, Monoclonal, Humanized
dc.subjectBiomarkers
dc.subjectProof of Concept Study
dc.titleProtocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.
dc.typeArticle
prism.issueIdentifier9
prism.publicationDate2018
prism.publicationNameBMJ Open
prism.startingPagee025333
prism.volume8
dc.identifier.doi10.17863/CAM.30448
dcterms.dateAccepted2018-08-16
rioxxterms.versionofrecord10.1136/bmjopen-2018-025333
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-09-21
dc.contributor.orcidKhandaker, Golam M [0000-0002-4935-9220]
dc.identifier.eissn2044-6055
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
pubs.funder-project-idWellcome Trust (201486/Z/16/Z)
pubs.funder-project-idMedical Research Council (MR/N019067/1)
cam.issuedOnline2018-09-21


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International