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

Stroke Clinical Trial

— Neurodoc  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04035655
• Other study ID #: 2013-A01385-40
• Status: Completed
• Phase: N/A
• Start date: October 2015
• Est. completion date: September 2018

Study information

• Verified date: July 2019
• Source: Groupe Hospitalier Pitie-Salpetriere
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Anoxic Brain Injury
• Brain Injuries
• Brain Injuries, Traumatic
• Consciousness Disorders
• Disorder of Consciousness
• Stroke
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

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).

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

Locations

Country	Name	City	State
France	Groupe Hospitalier Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Hospitalier Pitie-Salpetriere

Country where clinical trial is conducted

France, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Support vector machine multivariate prediction of consciousness from resting state EEG markers	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)
Primary	Evoked response potential during auditory oddball paradigm	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	Resting state EEG individual markers	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)
Secondary	State of consciousness	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)