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CONsciousness Transcranial Electric STimulation (CONTEST_3)

Primary Purpose

Disorder of Consciousness

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
In-phase 6 Hz prefronto-parietal tACS
Sham prefronto-parietal tACS
2 mA left prefrontal tDCS
Sham left prefrontal tDCS
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Disorder of Consciousness focused on measuring State of consciousness, tACS, tDCS, Global neuronal workspace, Brain injury

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Institut du Cerveau et de la Moelle - CR-ICM U 975 / UMRS INSERM 1127Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Sham Comparator

Experimental

Sham Comparator

Arm Label

In-phase 6 Hz prefronto-parietal tACS

Sham prefronto-parietal tACS

2 mA left prefrontal tDCS

Sham left prefrontal tDCS

Arm 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°.

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.

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.

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.

Outcomes

Primary Outcome Measures

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. This change in state of consciousness will be compared between active stimulation and sham stimulation

Secondary Outcome Measures

Evoked response potential during local-global paradigm
Change of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009)
Resting state EEG
Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014)

Full Information

First Posted
June 11, 2018
Last Updated
January 8, 2019
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT03576248
Brief Title
CONsciousness Transcranial Electric STimulation
Acronym
CONTEST_3
Official Title
Effect of Transcranial Electrical Stimulation on the Consciousness of Non-communicating Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 19, 2018 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Disorder of Consciousness
Keywords
State of consciousness, tACS, tDCS, Global neuronal workspace, Brain injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Study will be double-blind : neither participant nor the investigator will know which stimulation type (in-phase active, anti-phase active or sham) is on.
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
In-phase 6 Hz prefronto-parietal tACS
Arm Type
Experimental
Arm 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°.
Arm Title
Sham prefronto-parietal tACS
Arm Type
Sham Comparator
Arm 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.
Arm Title
2 mA left prefrontal tDCS
Arm Type
Experimental
Arm 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.
Arm Title
Sham left prefrontal tDCS
Arm Type
Sham Comparator
Arm 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.
Intervention Type
Device
Intervention Name(s)
In-phase 6 Hz prefronto-parietal tACS
Intervention Description
tACS is a non-invasive stimulation technique that works by delivering a weak sinusoidally oscillating electrical current to the surface of the skull to entrain oscillations in the brain.
Intervention Type
Device
Intervention Name(s)
Sham prefronto-parietal tACS
Intervention Description
tACS is a non-invasive stimulation technique that works by delivering a weak sinusoidally oscillating electrical current to the surface of the skull to entrain oscillations in the brain.
Intervention Type
Device
Intervention Name(s)
2 mA left prefrontal tDCS
Intervention Description
tDCS is a form of neuromodulation method where very low levels of constant current are delivered to specifically targeted areas of the brain
Intervention Type
Device
Intervention Name(s)
Sham left prefrontal tDCS
Intervention Description
tDCS is a form of neuromodulation method where very low levels of constant current are delivered to specifically targeted areas of the brain
Primary Outcome Measure Information:
Title
State of consciousness
Description
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. This change in state of consciousness will be compared between active stimulation and sham stimulation
Time Frame
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
Secondary Outcome Measure Information:
Title
Evoked response potential during local-global paradigm
Description
Change of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009)
Time Frame
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)
Title
Resting state EEG
Description
Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014)
Time Frame
Two time points: immediately before (baseline) and immediately after stimulation (post-stimulation)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lionel Naccache, MD, PhD
Phone
+33157274092
Email
lionel.naccache@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Bertrand Hermann, MD
Phone
+33157274318
Email
bertrand.hermann@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacobo D Sitt, MD, PhD
Organizational Affiliation
CR-ICM U 975 /UMRS INSERM 1127
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lionel Naccache, MD, PhD
Organizational Affiliation
CR-ICM U 975 /UMRS INSERM 1127
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bertrand Hermann, MD
Organizational Affiliation
CR-ICM U 975 /UMRS INSERM 1127
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut du Cerveau et de la Moelle - CR-ICM U 975 / UMRS INSERM 1127
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lionel Naccache, MD, PhD
Phone
01.57.27.40.92.
Email
lionel.naccache@icm-institute.org
First Name & Middle Initial & Last Name & Degree
Jacobo D Sitt, MD, PhD
Phone
01.57.27.43.21
Email
jacobo.sitt@icm-institute.org

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24574549
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.
Results Reference
background
PubMed Identifier
22683259
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.
Results Reference
background
PubMed Identifier
11839831
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.
Results Reference
background
PubMed Identifier
16350986
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.
Results Reference
background

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CONsciousness Transcranial Electric STimulation

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