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

NCT ID: NCT04035655

Last Updated: 2019-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2018-09-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Disorder of Consciousness Traumatic Brain Injury Anoxic Brain Injury Stroke

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Electrophysiological evaluation of a routine care intervention: single session of left dorso-lateral transcranial direct current stimulation
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Coma Recovery Scale - revised

Intervention Type 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).

Electrophysiological recordings

Intervention Type 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

Interventions

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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).

Intervention Type BEHAVIORAL

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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CRS-R EEG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role lead

Responsible Party

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LIONEL NACCACHE

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lionel Naccache, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Site Status

Countries

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France

References

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Angelakis E, Liouta E, Andreadis N, Korfias S, Ktonas P, Stranjalis G, Sakas DE. Transcranial direct current stimulation effects in disorders of consciousness. Arch Phys Med Rehabil. 2014 Feb;95(2):283-9. doi: 10.1016/j.apmr.2013.09.002. Epub 2013 Sep 11.

Reference Type BACKGROUND
PMID: 24035769 (View on PubMed)

Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.

Reference Type BACKGROUND
PMID: 24574549 (View on PubMed)

Thibaut A, Wannez S, Donneau AF, Chatelle C, Gosseries O, Bruno MA, Laureys S. Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state. Brain Inj. 2017;31(4):466-474. doi: 10.1080/02699052.2016.1274776. Epub 2017 Mar 10.

Reference Type BACKGROUND
PMID: 28281845 (View on PubMed)

Martens G, Lejeune N, O'Brien AT, Fregni F, Martial C, Wannez S, Laureys S, Thibaut A. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimul. 2018 Sep-Oct;11(5):982-990. doi: 10.1016/j.brs.2018.04.021. Epub 2018 May 2.

Reference Type BACKGROUND
PMID: 29759943 (View on PubMed)

Giacino JT, Kalmar K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):166-74. doi: 10.1080/09602010443000498.

Reference Type BACKGROUND
PMID: 16350959 (View on PubMed)

Sitt JD, King JR, El Karoui I, Rohaut B, Faugeras F, Gramfort A, Cohen L, Sigman M, Dehaene S, Naccache L. Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state. Brain. 2014 Aug;137(Pt 8):2258-70. doi: 10.1093/brain/awu141. Epub 2014 Jun 11.

Reference Type BACKGROUND
PMID: 24919971 (View on PubMed)

Engemann DA, Raimondo F, King JR, Rohaut B, Louppe G, Faugeras F, Annen J, Cassol H, Gosseries O, Fernandez-Slezak D, Laureys S, Naccache L, Dehaene S, Sitt JD. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain. 2018 Nov 1;141(11):3179-3192. doi: 10.1093/brain/awy251.

Reference Type BACKGROUND
PMID: 30285102 (View on PubMed)

Bekinschtein TA, Dehaene S, Rohaut B, Tadel F, Cohen L, Naccache L. Neural signature of the conscious processing of auditory regularities. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1672-7. doi: 10.1073/pnas.0809667106. Epub 2009 Jan 21.

Reference Type BACKGROUND
PMID: 19164526 (View on PubMed)

Faugeras F, Rohaut B, Weiss N, Bekinschtein T, Galanaud D, Puybasset L, Bolgert F, Sergent C, Cohen L, Dehaene S, Naccache L. Event related potentials elicited by violations of auditory regularities in patients with impaired consciousness. Neuropsychologia. 2012 Feb;50(3):403-18. doi: 10.1016/j.neuropsychologia.2011.12.015. Epub 2012 Jan 3.

Reference Type BACKGROUND
PMID: 22230230 (View on PubMed)

Other Identifiers

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2013-A01385-40

Identifier Type: -

Identifier Source: org_study_id

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