Clinical trial NCT03576248: CONsciousness Transcranial Electric STimulation
Official title: Effect of Transcranial Electrical Stimulation on the Consciousness of Non-communicating Patients.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Disorder of Consciousness
Keywords: State of consciousness
tACS
tDCS
Global neuronal workspace
Brain injury
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2018-07-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study is composed of two independent sub-studies, one exploring the effects of tACS and the other the effects of tDCS, with different participants assigned to the two sub-studies. There will be 2 arms in tACS group and 2 arms in tDCS group. Among each sub-study, all participants will participate in all arms (hence the cross-over design).
Primary purpose: TREATMENT

Brief summary: The aim of this study is to investigate the effect of transcranial Alternating Current Stimulation (tACS) at theta frequency and the the effect of transcranial Direct Current Stimulation (tDCS) on the conscious state of non-communicating patients. tACS and tDCS are non-invasive stimulation techniques that are used to induce brain oscillations at certain frequency or to increase the brain activity in applied region.

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 optimal intensity of electrical current stimulation remains unknown and transcranial Alternative Current Stimulation (tACS), with the ability to stimulate cortex at specific frequencies and to manipulate phase-synchrony between regions is a promising techniques to improve patients' consciousness.

In this study, the investigators will use prefrontal tDCS and theta tACS to improve patients consciousness level.

Detailed description: This study is constituted of two independent sub-studies investigating two types of stimulation (tDCS and tACS) with the same cross-over design

Study design The study design is composed of two experimental sessions, one active stimulation and one sham comparator. Sessions will be randomized in a double-blind randomized crossover design (neither the participant nor the experimenter knows which session includes which stimulation type), with at least 2 days of interval between them.

In these sessions, the patients' state of consciousness participants will first be determined using the dedicated Coma Recovery Scale - Revised (Giacino, Neurology 2002) (CRS-R) scale before stimulation. Resting state brain activity EEG and cognitive auditory paradigm (local-global paradigm, Bekinschtein, PNAS 2009) will also be recorded before stimulation.

Twenty minutes stimulation will then be performed (see below). CRS-R, resting state EEG and local-global paradigm will be repeated after stimulation.

Outcome measures will be the same in the two studies. The primary outcome will be the change of CRS-R between before and after stimulation. Secondary outcomes will be the neurophysiological correlates of consciousness in resting state EEG and during the local global paradigm.

tACS stimulation During tACS sessions, 6 Hz stimulation (1000 μA) will be applied simultaneously over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) and the left parietal cortex (P3) using an 8-channels stimulator (Starstim NE, Neuroelectrics, Barcelona, Spain) with small round sponge electrodes (25 cm2 surface, maximal current density of 0.06 μA/cm2), controlled via Bluetooth. In the in-phase condition, the phase difference between the two stimulation sites will be 0° which will entrain synchronization between sites. In the sham condition, the stimulation will start with a current intensity of 1000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. Each stimulation session will take 20 minutes and the positions of stimulation electrodes and the duration of the stimulation will be kept identical for all conditions.

tDCS stimulation During tDCS session, 2000 μA stimulation will be applied over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system) (Starstim NE, Neuroelectrics, Barcelona, Spain) with small round sponge electrodes (25 cm2 surface, maximal current density of 0.06 μA/cm2), controlled via Bluetooth. In the sham condition, the stimulation will start with a current intensity of 2000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. Each stimulation session will take 20 minutes and the positions of stimulation electrodes and the duration of the stimulation will be kept identical for all conditions.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 80 years
* Non communicative patients with disorder of consciousness diagnosed by CRS-R (VS, MCS, exitMCS)
* Patients with stable clinical examination (even in intensive care)
* Brain injury confirmed by cerebral imaging (MRI or TDM)
* French social security affiliation
* Signed and informed consent by the patient or by a legal representant

Exclusion Criteria:

* Status epilepticus or uncontrolled epilepsy
* Severely neurodegenerative illnesses (Alzheimer disease, Lewy Body Dementia)
* Electrical stimulation contraindication (metallic intra-cranial implants, pacemaker or implantable cardioverter-defibrillator, cranial prosthesis)
* Pregnant, parturient or breastfeeding women- Patients underage

Primary outcomes:
measure: State of consciousness
timeFrame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
Secondary outcomes:
measure: Evoked response potential during local-global paradigm
timeFrame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
measure: Resting state EEG
timeFrame: Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut du Cerveau et de la Moelle - CR-ICM U 975 / UMRS INSERM 1127
Study officials:
affiliation: CR-ICM U 975 /UMRS INSERM 1127
name: Jacobo D Sitt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CR-ICM U 975 /UMRS INSERM 1127
name: Lionel Naccache, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CR-ICM U 975 /UMRS INSERM 1127
name: Bertrand Hermann, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Polania R, Nitsche MA, Korman C, Batsikadze G, Paulus W. The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol. 2012 Jul 24;22(14):1314-8. doi: 10.1016/j.cub.2012.05.021. Epub 2012 Jun 7.
citation: Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53. doi: 10.1212/wnl.58.3.349.
citation: Kalmar K, Giacino JT. The JFK Coma Recovery Scale--Revised. Neuropsychol Rehabil. 2005 Jul-Sep;15(3-4):454-60. doi: 10.1080/09602010443000425.