CONsciousness Transcranial Electric STimulation (CONTEST_3)

Institut National de la Santé Et de la Recherche Médicale, France

Status: Terminated

Conditions: Disorder of Consciousness

Treatments: Device: In-phase 6 Hz prefronto-parietal tACS; Device: 2 mA left prefrontal tDCS; Device: Sham prefronto-parietal tACS; Device: Sham left prefrontal tDCS

Study type: Interventional

Funder types: Other

Identifiers

NCT03576248

C17-56

2017-A02763-50 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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20 participants in 4 patient groups

In-phase 6 Hz prefronto-parietal tACS

Experimental group

Description:

6 Hz stimulation (1000 μA) with transcranial Alternative Current Stimulation (tACS) 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 of the 10-20 international scalp EEG system, with a return electrode in Cz) for 20 minutes. The phase difference between the two stimulation sites will be 0°.

Treatment:

Device: In-phase 6 Hz prefronto-parietal tACS

Sham prefronto-parietal tACS

Sham Comparator group

Description:

The same stimulation as in in-phase transcranial Alternative Current Stimulation tACS (6 Hz F3 and P3 stimulation with 0° phase difference) will start with a current intensity of 1000 μA lasting for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. The whole session duration is 20 minutes.

Treatment:

Device: Sham prefronto-parietal tACS

2 mA left prefrontal tDCS

Experimental group

Description:

2000 μA anodal transcranial Direct Current Stimulation (tDCS) will be applied over the left prefrontal dorso-lateral cortex (F3 of the 10-20 international scalp EEG system with a right supraorbital return electrode (Fp2 of the 10-20 international scalp EEG system) during 20 minutes.

Treatment:

Device: 2 mA left prefrontal tDCS

Sham left prefrontal tDCS

Sham Comparator group

Description:

The same stimulation as active transcranial Direct Current Stimulation (tDCS) (anodal F3 and return in Fp2) will start at 2 mA intensity for 30 seconds. Afterwards, the intensity will progressively decrease over 20 seconds until cessation. The whole session duration is 20 minutes.

Treatment:

Device: Sham left prefrontal tDCS