Excitatory Prefrontal Weak Current Stimulation in Vegetative Patients (VEG-TDCS)

Excitatory Prefrontal Weak Current Stimulation in Vegetative Patients:Potential to Induce Modulation in Neurocognitive Features of Awareness

In response to "conscious" EEG findings related to detectable cognitive function that reliably denote awareness in vegetative state patients, in the current study, we will assess the covert conscious EEG activity (as well as standard clinical overt measures) and neuroplasctic propensity (i.e., changes in EEG spectral power synchronization values following tDCS intervention) in vegetative-state patients receiving repetitive transcranial direct current stimulation (tDCS) treatment over frontal motor areas for a period of two weeks. In support of this approach, a recent tDCS study with vegetative and minimally conscious patients implied that a twenty minutes anodal stimulation (i.e., excitatory stimulation) to the left dorsolateral prefrontal cortex (DLPFC) significantly increased CRS-R scores versus sham (placebo: non-active stimulation) stimulation condition. It was noted that this tDCS effect was more pronounced in minimally conscious state patients versus vegetative state patients excluding effects of chronicity or etiology. Thus, the investigators in this study suggested that tDCS could be effective in improving cognitive recovery in severely brain-injured patients. However, their findings would benefit neural activation correlates that could support their conclusion regarding the effectiveness of this type of non-invasive intervention in promoting neurocognitive recovery. Most importantly, tDCS is safe for use in humans, has no adverse effects, is considered the most non-invasive transcranial stimulation method because it uses extremely weak currents (0.5 to 2 mA), and, is known to only temporarily shift the neuron's membrane potential towards excitation/inhibition. In regard to the method's potential to induce functional recovery in vegetative state patients, recent clinical studies indicate that tDCS could counteract the negative effects of brain damage by influencing neurophysiological mechanisms, and is likely to contribute to the "formation of functionally meaningful connections and the maintenance of existing pathways" .

Study Overview

• Status: Completed
• Conditions: Disorder of Consciousness; Trauma, Brain; Vegetative State; MMN; Modification of Cognitive Status Indication; Anoxic Brain Damage; EEG; Paroxysms, Occipital, Epilepsy of Childhood; Cortical Atrophy
• Intervention / Treatment: Device: Transcranial direct current stimulation

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 91035
    • Herzog Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Anoxic brain damage/TBI/CVA/progressive dementia/encephalopathy
• Vegetative state patients or minimally conscious state according to CRS-R criteria
• Ages 18 to 90
• Consent for participation in clinical study (e.g., informed consent) by legal guardian of patients.

Exclusion Criteria:

• Intracranial metal implants
• Implanted devices that may be affected by tDCS (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
• Active medical condition that would preclude medical stability for the study, including significant ECG abnormalities, cardiac arrhythmia, uncontrolled high blood pressure
• Participation in other research studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active treatment; open label experimental treatment	Device: Transcranial direct current stimulation; Non-invasive brain stimulation or neuromodulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
JFK COMA RECOVERY SCALE - REVISED	JFK Coma recovery Scale - Revised scores for diagnosing disorders of consciousness. This cynical assessment scale examines reflexive behaviors such as response to pain and startle, and touch. The CRS consists of 25 hierarchically arranged items that comprise 6 subscales addressing auditory, visual, motor, oro- motor, communication, and arousal processes. Scoring is based on the presence or absence of specific behavioral responses to sensory stimuli administered in a standardized manner. The lowest item on each subscale represents reflexive activity, whereas the highest items represent cognitively mediated behaviors. sub scales represent motor function, auditory function, visual function sub scales and arousal sub scales. The low scores indicate low levels of functioning and the higher score indicate high levels of function an awareness. Maximum score is 23 and a minimal score is 0.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMN ERP amplitudes	Prefronal-Temopral cortex neuroplasticity and reactivity to sound : size of early auditory processing ERP amplitudes. If the negative change in ERP amplitudes is larger than in indicates better change-detection and neurplasticity.	2 weeks

Collaborators and Investigators

• Sponsor: Oded Meiron
• Collaborators: Neurosteer Ltd.
• Investigators: Principal Investigator: Efraim Jaul, MD, Herzog Medical Center

Publications and helpful links

General Publications

• Angelakis E, Liouta E, Andreadis N, Korfias S, Ktonas P, Stranjalis G, Sakas DE. Transcranial direct current stimulation effects in disorders of consciousness. Arch Phys Med Rehabil. 2014 Feb;95(2):283-9. doi: 10.1016/j.apmr.2013.09.002. Epub 2013 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2014
• Primary Completion (Actual): December 27, 2023
• Study Completion (Actual): December 27, 2023

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: October 30, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Damage, Chronic; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms, Respiratory; Unconsciousness; Hypoxia; Brain Injuries; Brain Injuries, Traumatic; Consciousness Disorders; Hypoxia, Brain; Persistent Vegetative State
• Other Study ID Numbers: 335-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Treatment methods and diagnostic methods will be shared as well as change in clinical and neurological status via research publication.

Drug and device information, study documents

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