Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness

NCT04065386 | Completed DMC

• 1 other identifier: 2019/91
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

Non-invasive brain stimulations techniques have recently shown promising results in patients with disorders of consciousness. Notably, a case reported improvement of level of consciousness using transcutaneous auricular vagal nerve stimulation in a patient in unresponsive wakefulness syndrome. Here we aim to assess the effects of transcutaneous auricular vagal nerve stimulation on post-coma patients with disorders of consciousness in a first randomized controlled trial. To measure these effects, behavioral (Coma recovery scale revised - CRS-R -primary outcome) and neuro-electrophysiological (electroencephalography - EEG - secondary outcome) data will be recorded in severely brain-injured patients with DOC.

Conditions

Minimally Conscious State; Vegetative State; Consciousness Disorder

Keywords

Vagus nerve stimulation; Transcutaneous electrical nerve stimulation; Non-invasive brain stimulation; Neuromodulation; High-density EEG; Unresponsive wakefulness syndrome; Vegetative state; Minimally Conscious state; Consciousness disorder

Outcome Measures

Primary Outcomes (1)

• Change in CRS-R total score and index score

  Behavioral improvement measured by standardized scale. This scale is ranging from 0 to 23, highest score represents more signs of consciousness. The index score is ranging from 0 to 100.

  Before the installation of the EEG equipment in the pre-stimulation period and 5 minutes after the post-stimulation resting state EEG (immediately after removing the equipment).

Secondary Outcomes (1)

• Change in EEG

  15 min before the stimulation period and 15 min after the stimulation period.

Study Arms (2)

Active taVNS

ACTIVE COMPARATOR

Patients will receive 5 days of transcutaneous auricular vagal nerve stimulation (taVNS) bilaterally, at the cymba conchae, the active localization. It will be preceded and followed by a clinical assessment (Coma Recovery Scale- Revised) and a neurophysiological assessment (128/256 channels EEG and electrocardiograph) the first and last day of stimulation.

Device: Active taVNS

Sham taVNS

PLACEBO COMPARATOR

Patients will receive 5 days of transcutaneous auricular vagal nerve stimulation (taVNS) bilaterally, at the ear lobe, the sham localization. It will be preceded and followed by a clinical assessment (Coma Recovery Scale- Revised) and a neurophysiological assessment (128/256 channels EEG and electrocardiograph) the first and last day of stimulation.

Device: sham taVNS

Interventions

Active taVNS DEVICE

Patients will receive transcutaneous auricular vagal nerve stimulation (taVNS) for 5 consecutive days, at the cymba conchae, bilaterally, during 45 minutes (alternating 30 s on and 30 s off periods). Current intensity: 3 mA or less according to the participant's pain threshold, width: 200-300 μsec.

Active taVNS

sham taVNS DEVICE

Patients will receive transcutaneous auricular vagal nerve stimulation (taVNS) for 5 consecutive days, at the ear lobe, bilaterally, during 45 minutes (alternating 30 s on and 30 s off periods). Current intensity: 3 mA or less according to the participant's pain threshold, width: 200-300 μsec.

Sham taVNS

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• State of consciousness: unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) as defined by CRS-R performed during the screening period.
• Cerebral damage of known etiology
• Time since injury between 7 and 90 days
• Intact skin at the ears
• Consent given by the substitute decision maker

You may not qualify if:

• Anyone who is deemed medically unsuitable for this study as determined by a physician involved with the study (e.g. severe rythmic heart condition)
• Previous history of neurological disorders
• Documented pregnancy
• Active implant (i.e. pacemaker)
• Profound sedation such as one caused by general anaesthetics (e.g., propofol) or a combination of central acting sedatives (e.g., benzodiazepines, opioids)

Sponsors & Collaborators

• University of Liege: lead

Study Sites (2)

Centre Neurologique William Lennox

Ottignies-Louvain-la-Neuve, Brabant Wallon, 1340, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, Liège, 4000, Belgium

Location

Related Publications (3)

• Yu YT, Yang Y, Wang LB, Fang JL, Chen YY, He JH, Rong PJ. Transcutaneous auricular vagus nerve stimulation in disorders of consciousness monitored by fMRI: The first case report. Brain Stimul. 2017 Mar-Apr;10(2):328-330. doi: 10.1016/j.brs.2016.12.004. Epub 2016 Dec 14. No abstract available.

  PMID: 28017322 BACKGROUND

• Yakunina N, Kim SS, Nam EC. Optimization of Transcutaneous Vagus Nerve Stimulation Using Functional MRI. Neuromodulation. 2017 Apr;20(3):290-300. doi: 10.1111/ner.12541. Epub 2016 Nov 29.

  PMID: 27898202 BACKGROUND

• Vitello MM, Briand MM, Ledoux D, Annen J, El Tahry R, Laureys S, Martin D, Gosseries O, Thibaut A. Transcutaneous vagal nerve stimulation to treat disorders of consciousness: Protocol for a double-blind randomized controlled trial. Int J Clin Health Psychol. 2023 Apr-Jun;23(2):100360. doi: 10.1016/j.ijchp.2022.100360. Epub 2022 Nov 29.

  PMID: 36467262 DERIVED

MeSH Terms

Conditions

Consciousness Disorders; Persistent Vegetative State

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness

Study Officials

• Aurore Thibaut, PhD

  Université de Liège

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 22, 2019
• Study Start: February 9, 2022
• Primary Completion: September 21, 2024
• Study Completion: December 21, 2024
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)