tDCS in Patients With Disorder of Consciousness Due to Severe Acquired Brain Injury

Observational Study on the Use of Transcranial Direct Stimulation in Patients With Disorder of Consciousness, Due to Severe Acquired Brain Injury, to Stimulate Recovery of Consciousness

The present observational study is aimed at reporting the short-, mid- and long-term outcomes of patients with Disorder of Consciousness (DOC), in Vegetative State (VS) or Minimally Conscious State (MCS), due to a severe Acquired Brain Injury (sABI), after repeated treatments with anodal Transcranial Direct Current Stimulation (tDCS) on Left Dorsolateral Prefrontal Cortex (L-DLPFC), to stimulate recovery of consciousness. The results obtained will also be compared with those of a historical control cohort, before the introduction of tDCS, matched for demographic and clinical characteristics.

Study Overview

• Status: Terminated
• Conditions: Brain Injuries; Cognitive Impairment; Consciousness Disorders; Minimally Conscious State; Vegetative State
• Intervention / Treatment: Device: Anodal tDCS; Other: Usual care

Detailed Description

Patients surviving sABI resulting in a coma state, thanks to improvements in early intervention and intensive care technologies, in some cases begin to regain vigilance and consciousness within few weeks from the event. In other cases, however, while regaining vigilance, they may continue to present a DOC state. DOC patients, by definition, are unable to communicate and have severe motor, sensory and cognitive deficits. They can be in a Vegetative State (VS), characterized by wakefulness without consciousness, which can favorably evolve in a Minimally Conscious State (MCS).

Although there are currently no evidence-based guidelines on the treatment of DOC patients to facilitate their recovery of consciousness, several studies published in recent years have focused on various pharmacological and non-pharmacological interventions. Among these, there is a non-invasive stimulation technique, the Transcranial Direct Current Stimulation (tDCS), which has long been known for other indications. tDCS affects the neuronal membrane rest potential and is able to neuromodulate cortical excitability. Protocols in the literature describing the use of tDCS in DOC patients envisage anodal stimulation (active electrode) on the L-DLPFC area, with the reference electrode placed on a homologous controlateral area or on the controlateral shoulder. tDCS variants have also been described, both by type of current delivered and by active electrode's positioning, but they are still experimental.

The Montecatone Rehabilitation Institute (a 3rd level Italian hospital, specialized in intensive rehabilitation of sABI and spinal cord injured patients) has recently started adopting tDCS in clinical practice to stimulate recovery of consciousness of VS or MCS, post-sABI, patients. Since it was already known that a single tDCS applications is not sufficient to elicit detectable and durable responses, the Montecatone Institute's protocol envisages anode application on L-DLPFC area in a 20 minute daily session, possibly for 2 consecutive weeks (5 consecutive days per week). For a gradual and safe approach, 1 milliampere (mA) current intensity is applied during the first week, 2 mA during the second week.

The post-sABI DOC patients treated with tDCS at the Montecatone Institute, compared with the known literature, are more homogeneous with regard to the distance of time from the lesional event, moreover tDCS is administered at an earlier stage. The present observational, longitudinal study is aimed therefore at reporting the outcomes of such DOC patients treated with tDCS by evaluating them with functional and cognitive impairment scales, at short-term (at the conclusion of the first and second week of tDCS treatment), medium-term (3 months after the end of the treatment) and long-term (6 months after the end of the treatment). Electroencephalographic (EEG) pattern data will also be collected. The outcome data obtained will be compared with those of a historical control cohort too, matched for demographic and clinical characteristics. The present study aims at covering the lack in the literature of long-term follow-up data too.

It is expected that the results of the present study may be useful to provide concrete indications for planning further research studies aimed at evaluating the effectiveness of different techniques and/or protocols for application of tDCS in post-sABI DOC patients.

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• Italy
  • BO
    • Imola, BO, Italy, 40026
      • Montecatone Rehabilitation Institute S.p.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive DOC patients admitted to the sABI Operative Unit of the Montecatone Rehabilitation Institute

Description

Inclusion Criteria:

• patients with Disorder of Consciousness, VS (= LCF 2) or MCS (= LCF 3), due to sABI;
• any etiology, with the exception of extensive haemorrhagic lesions;
• stable clinical conditions.

Exclusion Criteria:

• presence of implanted devices (e.g. pacemakers, intrathecal infusers);
• presence of metallic brain implants (clips) or intracranial implants;
• presence of extensive craniotomy involving the area of application of tDCS;
• history of epileptic seizure;
• mechanical ventilation in place;
• history of psychotic disorders;
• severe neurodegenerative pathology;
• pharmacotherapy with Na+ or Ca++ channel blockers (e.g. Carbamazepine) or with N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. Dextromethorphan);
• pregnancy in progress.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
tDCS cohort; DOC patients treated according to usual care, plus anodal tDCS (prospective cohort)	Device: Anodal tDCS; Anodal tDCS, on L-DLPFC area, is started 2 weeks after admission to the sABI Operative Unit with: one session per day (in the morning), possibly for 5 consecutive days per week (from Monday to Friday), for 2 consecutive weeks. Each tDCS session lasts 20 minutes. Current intensity is 1 mA during the first week, 2 mA in the second week; Other: Usual care; Usual care of DOC patients
Historical control cohort; DOC patients treated according to usual care only (retrospective cohort of patients matched for demographic and clinical characteristics, admitted at the Montecatone Rehabilitation Institute no more than 3 years before the introduction of tDCS)	Other: Usual care; Usual care of DOC patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coma recovery in the tDCS cohort (short- and mid-term outcomes)	Assessment by Coma Recovery Scale-Revised (CRS-R) (on-line, where tDCS is administered)	Baseline (initial visit); tDCS session 5 (1 week); tDCS closing session 10 (2 weeks); follow-up 1 (1 week after tDCS closing session 10); follow-up 2 (3 months after tDCS closing session 10)
Change in cognitive functioning level in the tDCS cohort (short- and mid-term outcomes)	Assessment by Levels of Cognitive Functioning Scale (LCF) (off-line, i.e. where tDCS is administered, immediately after tDCS session)	Baseline (initial visit); tDCS session 5 (1 week); tDCS closing session 10 (2 weeks); follow-up 1 (1 week after tDCS closing session 10); follow-up 2 (3 months after tDCS closing session 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coma recovery in the tDCS cohort (long-term outcome)	Assessment by CRS-R scale	Baseline (initial visit); follow-up 3 (6 months after tDCS closing session 10)
Change in cognitive functioning level in the tDCS cohort (long-term outcome)	Assessment by LCF scale	Baseline (initial visit); follow-up 3 (6 months after tDCS closing session 10)
Change in disability level in the tDCS cohort (short-, mid- and long-term follow-up)	Assessment by Rappaport's Disability Rating Scale (DRS)	Baseline (initial visit); follow-up 1 (1 week after tDCS closing session 10); follow-up 2 (3 months after tDCS closing session 10); follow-up 3 (6 months after closing session 10)
Change in electroencephalography pattern in the tDCS cohort	Assessment by electroencephalography (EEG) (off-line, i.e. where tDCS is administered, immediately after tDCS session)	Baseline (initial visit); tDCS tDCS closing session 10 (2 weeks)
Change in coma recovery between the tDCS cohort and the Historical control cohort	Assessment by CRS-R scale	Baseline (initial visit); 3 months; 6 months
Change in cognitive functioning level between the tDCS cohort and the Historical control cohort	Assessment by LCF scale	Baseline (initial visit); 3 months; 6 months
Change in disability level between the tDCS cohort and the Historical control cohort	Assessment by DRS scale	Baseline (initial visit); 3 months; 6 months

Collaborators and Investigators

• Sponsor: Montecatone Rehabilitation Institute S.p.A.
• Investigators: Principal Investigator: Angela Morreale, MD, Montecatone Rehabilitation Institute S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: tDCS; transcranial direct current stimulation; acquired brain injury; coma; vigilance
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Damage, Chronic; Craniocerebral Trauma; Trauma, Nervous System; Unconsciousness; Brain Injuries; Wounds and Injuries; Consciousness Disorders; Persistent Vegetative State
• Other Study ID Numbers: CE-17101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No