Skip to main content
OpenTrials
Completed

NCT Number: NCT04035655

Sub-study of the NEURODOC Project : Neurophysiological Evaluation of a Routine Care Open Label tDCS Session

Limited treatments are available to improve consciousness in severely brain injured patients. Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed evidence of efficacy to increase level of consciousness and functional communication in some Minimally Conscious State (MCS) patients, and in some Vegetative State (VS) patients.

However the mechanisms by which tDCS improves consciousness are poorly understood and the electrophysiological effects of such a stimulation have never been studied in disorders of consciousness patients.

In this study, the investigators will use detailed clinical examinations and electrophysiological assessments (quantitative high-density EEG and event-related potentials) to assess the effect of a open-label single session of left dorsolateral prefrontal cortex tDCS stimulation administered as routine care.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Disorder of Consciousness Anoxic Brain Injury Brain Diseases Brain Injuries Brain Injuries, Traumatic Brain Ischemia Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Consciousness Disorders Craniocerebral Trauma Hypoxia Hypoxia, Brain Hypoxia-Ischemia, Brain Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Respiratory Stroke Trauma, Nervous System Traumatic Brain Injury Vascular Diseases Wounds and Injuries

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

About this study

Limited treatments are available to improve consciousness in severely brain injured patients. Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed evidence of efficacy to increase level of consciousness and functional communication in some Minimally Conscious State (MCS) patients, and in some Vegetative State (VS) patients (1, 2, 3, 4), with no side effects reported.

However the mechanisms by which tDCS improves consciousness are poorly understood and the electrophysiological effects of the stimulation have never been studied in disorders of consciousness patients.

In this study, the investigators will use detailed clinical examinations (Coma Recovery Scale - Revised (5)) and electrophysiological assessments (quantitative high-density EEG and event-related potentials) (6, 7) and event-related potentials (8, 9) together with a standard morphological MRI to assess the effect of a open-label single session of left dorsolateral prefrontal cortex tDCS stimulation administered as routine care.

The primary goal is to investigate electrophysiological response to tDCS and its relation to behavioral response to better understand how tDCS affects consciousness in disorders of consciousness patients.

References:

  • Angelakis, E. et al. Transcranial Direct Current Stimulation Effects in Disorders of Consciousness. Arch. Phys. Med. Rehabil. 95, 283-289 (2014).
  • Thibaut, A., Bruno, M.-A., Ledoux, D., Demertzi, A. & Laureys, S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology 82, 1112-1118 (2014).
  • Thibaut, A. et al. Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state. Brain Inj. 1-9 (2017). doi:10.1080/02699052.2016.1274776
  • Martens, G. et al. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimulat. (2018). doi:10.1016/j.brs.2018.04.021
  • Giacino, J. T. & Kalmar, K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol. Rehabil. 15, 166-174 (2005).
  • Sitt, J. D. et al. Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state. Brain 137, 2258-2270 (2014).
  • Engemann, D. A. et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain J. Neurol. 141, 3179-3192 (2018).
  • Bekinschtein, T. A. et al. Neural signature of the conscious processing of auditory regularities. Proc. Natl. Acad. Sci. 106, 1672-1677 (2009).
  • Faugeras, F. et al. Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness. Neuropsychologia 50, 403-418 (2012).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age between 18 and 80 years
  • Disorder of consciousness assessed by CRS-R (VS, MCS, exitMCS)
  • Patients with stable clinical examination (even in intensive care unit)
  • Structural brain injury confirmed by cerebral imaging (MRI or TDM)

Exclusion criteria

  • Refractory status epilepticus
  • Known preexisting severe neurodegenerative disease (ie: Alzheimer disease, Lewy body dementia, ...)
  • MRI contraindication: metallic intra-cranial implants, pacemaker or implantable cardioverter-defibrillator, cranial prosthesis
  • Pregnant, parturient or breastfeeding women

Treatment and study plan

Coma Recovery Scale - revised

Behavioral

Assessment of the level of consciousness by the dedicated Coma Recovery Scale - Revised, current gold-standard in consciousness level assessment.

Assessment before and after the tDCS session (immediately before and after the electrophysiological assessment, see below).

Other names: CRS-R

Electrophysiological recordings

Diagnostic Test

The electrophysiological assessment consisted of:

  • a 5 minutes resting state high-density EEG recording
  • a approximately 6 minutes auditory oddball paradigm These two procedures were administered immediately before and after the tDCS session

Other names: EEG

Primary outcomes

  1. Support vector machine multivariate prediction of consciousness from resting state EEG markers

    Time frame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

    Change from baseline of the predicted probability of conscious state, ie. to be classified a in a 'minimally conscious state' as opposed to be classified as in a 'vegetative state'.

    The prediction will be based on a set of markers extracted from the EEG (power spectra, information theory, complexity and connectivity markers) and will use a support vector machine classifier algorithm train on a validated database. See Sitt et al., Brain et al. 2014. for details on the EEG preprocessing, markers extraction, support vector machine algorithm and training database.

  2. Evoked response potential during auditory oddball paradigm

    Time frame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

    Change of the Evoked Response Potentials recorded during the auditory oddball paradigm

Secondary outcomes

  1. Resting state EEG individual markers

    Time frame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

    In addition to the multivariate classification from the EEG, the response to stimulation will be evaluated on several quantitative markers derived from the EEG: power spectrum, complexity and connectivity assessed by the weighted symbolic mutual information (King & Sitt, Current Biology 2013; Sitt, Brain 2014; Engemann & Raimondo, Brain 2018)

  2. State of consciousness

    Time frame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

    Change of the Coma Recovery Scale-Revised scores (CRS-R, Giacino et al. Neurology 2002 and Kalmar et al., Neuropsychol Rehabil 2005) between before and after stimulation (CRS-R post stimulation - CRS-R before stimulation). The CRS-R score is a qualitative and quantitative scales ranking predefined behaviors elicited by the patients in the following six subscales, auditory function, visual function, motor function, verbal and oromotor function, communication and wakefulness, the sum of which give a total score ranging from 0 to 23. Higher values of the scale mean a better state of consciousness.

Sponsors and collaborators

Lead sponsor

Groupe Hospitalier Pitie-Salpetriere

Other

Registry information

Official study title

Sub-study of the NEURODOC Project (Electrophysiological Evaluation of Consciousness in Patients With Disorders of Consciousness During Standard Care Procedures): Neurophysiological Evaluation of a Routine Care Open Label tDCS Session

Acronym: Neurodoc

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Jul 29, 2019
Registry last updated
Jul 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.