Two Intensities of Transcranial Direct Current Stimulation to Improve Consciousness in Severely Brain Injured Patients (STIMCOM)

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.

This study will test the effects of two intensities of tDCS stimulation (either 0.2mA or 2mA) applied on left dorso-lateral prefrontal cortex on both behavior, - assessed by the Coma Recovery Scale-Revised (CRS-R) scores -, as well as quantified EEG recorded during resting state (using algorithms previously designed and published by the investigators) and event-related potentials (using auditory paradigms we previously published) in severely brain damaged patients with disorders of consciousness (MCS, VS, and conscious but cognitively disabled patients) of various etiologies.

Study Overview

• Status: Unknown
• Conditions: Cognitive Impairment; Disorder of Consciousness; Minimally Conscious State; Vegetative State
• Intervention / Treatment: Device: transcranial direct current stimulation (tDCS) / Comparison of current intensities

Detailed Description

This study will use a cross-over double-blind design with each patient receiving both current intensities in a randomized order during 4 weeks (2 weeks for each tDCS intensity, totalizing a number of 10X2 stimulation sessions of 20 minutes each).

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jacobo Sitt, MD PhD; Phone Number: +33 1 57 27 43 17; Email: jacobo.sitt@icm-institute.org
• Study Contact Backup: Name: Bertrand Hermann, MD Msc; Phone Number: +33 1 57 27 43 14; Email: bertrand.hermann@icm-institute.org

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Groupe Hospitalier Pitie-Salpetriere
    • Contact: Lionel Naccache, MD, PhD; Phone Number: +33157274314; Email: lionel.naccache@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non communicative patients (including conscious patients but presenting with major fluctuations of vigilance and/or of cognitive abilities)
• Patients with stable clinical examination
• Age between 18 and 80 years
• Brain injury confirmed by cerebral imaging (MRI or TDM)
• Disorder of consciousness diagnosed by CRS-R (VS, MCS, exitMCS)

Exclusion Criteria:

• Status epilepticus
• Severely neurodegenerative illnesses (Alzheimer disease, Lewy Body Dementia)
• Pregnancy
• Patients underage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2 mA anodal tDCS stimulation; Anodal tDCS stimulation at 2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks	Device: transcranial direct current stimulation (tDCS) / Comparison of current intensities
ACTIVE_COMPARATOR: 0.2 mA anodal tDCS stimulation; Anodal tDCS stimulation at 0.2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks	Device: transcranial direct current stimulation (tDCS) / Comparison of current intensities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the Coma Recovery Scale-Revised score according to tDCS current intensity (2mA versus 0.2mA)	Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at the tenth day of 2mA stimulation (Day14 or Day28)	Last Day of 0.2mA session (Day 14th or Day 28th) versus Last Day of 2mA session (Day 14th or Day 28th)
Change from baseline of the Coma Recovery Scale-Revised score after 2mA tDCS current intensity	Comparison of the CRS-R score at the tenth day of 2mA stimulation (Day14 or Day28) with the score at baselne (Day1)	Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
Change from baseline of the Coma Recovery Scale-Revised score after 0.2mA tDCS current intensity	Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at baselne (Day1)	Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IChange of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity	Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)	Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)
Change from baseline of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 2mA tDCS current intensity	Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 2mA tDCS stimulation	Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
Change from baseline of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 0.2mA tDCS current intensity	Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 0.2mA tDCS stimulation	Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
IChange of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity	Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)	Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)
Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity	Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th)	Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 0.2mA tDCS current intensity	Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)	Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere
• Collaborators: Hospices Civils de Lyon; Hôpital Raymond Poincaré
• Investigators: Study Director: Lionel Naccache, MD PhD, Paris 6 University ICM Inserm APHP

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (ANTICIPATED): January 1, 2021

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: December 28, 2016
• First Posted (ESTIMATE): January 2, 2017

Study Record Updates

• Last Update Posted (ESTIMATE): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 14, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: EEG; Transcranial direct current stimulation (tDCS); Consciousness; Vegetative state; Minimally conscious state; Disorder of consciousness; Exit-MCS; CRS-R; Cognitive ERPs
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Damage, Chronic; Unconsciousness; Consciousness Disorders; Persistent Vegetative State
• Other Study ID Numbers: SC20160427