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

NCT04035655 | Completed FDA Device

• 1 other identifier: 2013-A01385-40
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Disorder of Consciousness; Traumatic Brain Injury; Anoxic Brain Injury; Stroke

Keywords

Disorders of consciousness; Transcranial direct current stimulation; Electroencephalography; Electrophysiological signatures of consciousness; Coma Recovery Scale - Revised

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (2)

• Resting state EEG individual markers

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

• State of consciousness

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

Study Arms (1)

Clinical and electrophysiological evaluation of tDCS session

EXPERIMENTAL

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; Diagnostic Test: Electrophysiological recordings

Interventions

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).

Also known as: CRS-R

Clinical and electrophysiological evaluation of tDCS session

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

Also known as: EEG

Clinical and electrophysiological evaluation of tDCS session

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Groupe Hospitalier Pitie-Salpetriere: lead

Study Sites (1)

Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

Location

Related 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.

  PMID: 24035769 BACKGROUND

• 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.

  PMID: 24574549 BACKGROUND

• 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.

  PMID: 28281845 BACKGROUND

• 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.

  PMID: 29759943 BACKGROUND

• 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.

  PMID: 16350959 BACKGROUND

• 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.

  PMID: 24919971 BACKGROUND

• 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.

  PMID: 30285102 BACKGROUND

• 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.

  PMID: 19164526 BACKGROUND

• 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.

  PMID: 22230230 BACKGROUND

MeSH Terms

Conditions

Consciousness Disorders; Brain Injuries, Traumatic; Hypoxia-Ischemia, Brain; Stroke

Interventions

Electroencephalography

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Ischemia; Cerebrovascular Disorders; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Lionel Naccache, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Electrophysiological evaluation of a routine care intervention: single session of left dorso-lateral transcranial direct current stimulation

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 29, 2019
• Study Start: October 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: July 29, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)