TY - JOUR

T1 - Detecting signatures of consciousness in acute brain injury after stimulation with apomorphine and methylphenidate

T2 - Protocol for a placebo-controlled, randomized, cross-over study

AU - Othman, Marwan H.

AU - Møller, Kirsten

AU - Kjaergaard, Jesper

AU - Kondziella, Daniel

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2024

Y1 - 2024

N2 - Introduction Acute brain injury can lead to states of decreased consciousness, that is, disorder of consciousness (DoC). Detecting signs of consciousness early is vital for DoC management in the intensive care unit (ICU), neurorehabilitation and long-term prognosis. Our primary objective is to investigate the potential of pharmacological stimulant therapies in eliciting signs of consciousness among unresponsive or low-responsive acute DoC patients. Methods In a placebo-controlled, randomised, cross-over setting, we evaluate the effect of methylphenidate and apomorphine in 50 DoC patients with acute traumatic or non-traumatic brain injury admitted to the ICU. Patients are examined before and after administration of the trial drugs using (1) neurobehavioural scales to determine the clinical level of consciousness, (2) automated pupillometry to record pupillary responses as a signature for awareness and (3) near-infrared spectroscopy combined with electroencephalography to record neurovascular coupling as a measure for cortical activity. Primary outcomes include pupillary dilations and increase in cortical activity during passive and active paradigms. Ethics The study has been approved by the ethics committee (Journal-nr: H-21022096) and follows the principles of the Declaration of Helsinki. It is deemed to pose minimal risks and to hold a significant potential to improve treatment options for DoC patients. If the stimulants are shown to enhance cortical modulation of pupillary function and neurovascular coupling, this would warrant a large multicentre trial to evaluate their clinical impact. Dissemination Results will be available on EudraCT, clinicaltrialsregister.eu and published in an international peer-reviewed journal. Trial registration number EudraCT Number: 2021-001453-31.

AB - Introduction Acute brain injury can lead to states of decreased consciousness, that is, disorder of consciousness (DoC). Detecting signs of consciousness early is vital for DoC management in the intensive care unit (ICU), neurorehabilitation and long-term prognosis. Our primary objective is to investigate the potential of pharmacological stimulant therapies in eliciting signs of consciousness among unresponsive or low-responsive acute DoC patients. Methods In a placebo-controlled, randomised, cross-over setting, we evaluate the effect of methylphenidate and apomorphine in 50 DoC patients with acute traumatic or non-traumatic brain injury admitted to the ICU. Patients are examined before and after administration of the trial drugs using (1) neurobehavioural scales to determine the clinical level of consciousness, (2) automated pupillometry to record pupillary responses as a signature for awareness and (3) near-infrared spectroscopy combined with electroencephalography to record neurovascular coupling as a measure for cortical activity. Primary outcomes include pupillary dilations and increase in cortical activity during passive and active paradigms. Ethics The study has been approved by the ethics committee (Journal-nr: H-21022096) and follows the principles of the Declaration of Helsinki. It is deemed to pose minimal risks and to hold a significant potential to improve treatment options for DoC patients. If the stimulants are shown to enhance cortical modulation of pupillary function and neurovascular coupling, this would warrant a large multicentre trial to evaluate their clinical impact. Dissemination Results will be available on EudraCT, clinicaltrialsregister.eu and published in an international peer-reviewed journal. Trial registration number EudraCT Number: 2021-001453-31.

KW - CLINICAL NEUROLOGY

KW - COMA

KW - CONSCIOUSNESS

KW - INTENSIVE CARE

KW - TRAUMATIC BRAIN INJURY

U2 - 10.1136/bmjno-2023-000584

DO - 10.1136/bmjno-2023-000584

M3 - Journal article

C2 - 38268756

AN - SCOPUS:85182991267

VL - 6

JO - BMJ Neurology Open

JF - BMJ Neurology Open

SN - 2632-6140

IS - 1

M1 - e000584

ER -