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

July 25, 2019 updated by: LIONEL NACCACHE, Groupe Hospitalier Pitie-Salpetriere

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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:

  1. Angelakis, E. et al. Transcranial Direct Current Stimulation Effects in Disorders of Consciousness. Arch. Phys. Med. Rehabil. 95, 283-289 (2014).
  2. 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).
  3. 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
  4. 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
  5. Giacino, J. T. & Kalmar, K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol. Rehabil. 15, 166-174 (2005).
  6. 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).
  7. 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).
  8. Bekinschtein, T. A. et al. Neural signature of the conscious processing of auditory regularities. Proc. Natl. Acad. Sci. 106, 1672-1677 (2009).
  9. Faugeras, F. et al. Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness. Neuropsychologia 50, 403-418 (2012).

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Groupe Hospitalier Pitie-Salpetriere

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clinical and electrophysiological evaluation of tDCS session

In this prospective case-control study, the investigator's main goal was to evaluate the impact of a single standard-care tDCS session on brain activity (EEG).

The effect of a single 20 minutes 2 mA tDCS session with the anode placed over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital cortex administered as routine care were evaluated by combined behavioral and electrophysiological assessments immediately before and after the stimulation.

The study consisted of the following interventions, administered immediately before and after the stimulation session:

  • detailed behavioral assessment by the Coma Recovery Scale-Revised (CRS-R)
  • 5 minutes resting state high-density EEG recordings and 6 minutes auditory oddball paradigm immediately.

Additionally, clinical anatomical MRI (T1) acquired as routine care were used to model the estimated tDCS-induced electric fields in the entire head of patients, based on available T1-weighted MRI.
Behavioral: Coma Recovery Scale - revised

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
Diagnostic test: Electrophysiological recordings

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
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
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
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.
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Hospitalier Pitie-Salpetriere

Investigators

  • Principal Investigator: Lionel Naccache, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

September 1, 2018

Study Completion (Actual)

September 1, 2018

Study Registration Dates

First Submitted

July 23, 2019

First Submitted That Met QC Criteria

July 25, 2019

First Posted (Actual)

July 29, 2019

Study Record Updates

Last Update Posted (Actual)

July 29, 2019

Last Update Submitted That Met QC Criteria

July 25, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-A01385-40

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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