Multicentre longitudinal study of fluid and neuroimaging BIOmarkers of AXonal injury after traumatic brain injury: the BIO-AX-TBI study protocol

Neil Samuel Nyholm Graham, Karl A Zimmerman, Guido Bertolini, Sandra Magnoni, Mauro Oddo, Henrik Zetterberg, Federico Moro, Deborah Novelli, Amanda Heslegrave, Arturo Chieregato, Enrico Fainardi, Joanne M Fleming, Elena Garbero, Samia Abed-Maillard, Primoz Gradisek, Adriano Bernini, David J Sharp, Neil Samuel Nyholm Graham, Karl A Zimmerman, Guido Bertolini, Sandra Magnoni, Mauro Oddo, Henrik Zetterberg, Federico Moro, Deborah Novelli, Amanda Heslegrave, Arturo Chieregato, Enrico Fainardi, Joanne M Fleming, Elena Garbero, Samia Abed-Maillard, Primoz Gradisek, Adriano Bernini, David J Sharp

Abstract

Introduction and aims: Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome.

Methods and analysis: BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6 weeks, at 6 and 12 months after injury.

Ethics and dissemination: The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d'éthique de la recherche sur l'être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit.

Trial registration number: NCT03534154.

Keywords: biochemistry; magnetic resonance imaging; neurological injury; trauma management.

Conflict of interest statement

Competing interests: HZ has served at advisory boards for Eli Lilly, Roche Diagnostics and Pharmasum Therapeutics, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. The other authors have no potential conflicts to declare.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Recruitment status. Cumulative number of patients recruited into the BIO-AX-TBI study since its initiation, a total of 311 participants as of June 2020. BIO-AX-TBI, BIOmarkers of AXonal injury after traumatic brain injury.

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