Clinical trial NCT04065386: Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness
Official title: Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness: a Randomized Double-blind Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Consciousness Disorder
Minimally Conscious State
Vegetative State
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
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2019-08-22
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Currently, therapeutic options for severely brain-injured patients with disorders of consciousness (DOC), including patients in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are limited and still need to be improved to influence long-term outcomes. Non-invasive brain stimulations (NIBS) techniques have recently shown promising results in DOC.

Transcutaneous auricular vagal nerve stimulation (taVNS-R, tVNS Technologies GmbH, Germany) seems to be a promising approach. In a recent case report, a patient in UWS improved to MCS using this therapeutic technique.

To confirm this positive result, we propose a first randomized double-blind controlled trial. The patients will be randomized in the active stimulation group and will receive bilateral stimulations of the cymba conchae or in the sham stimulation group and will receive bilateral stimulations of the ear lobe. All stimulations will be performed for 45 minutes bilaterally for 5 consecutive days, between 7 and 90 days post-injury in severely brain-damaged patients with disorders of consciousness. The stimulation will start at 3 mA and will be decreased if signs of pain were observed (more than 4/9 according to the Nociceptive Coma Scale-Revised - NCS-R) until stimulation stays under pain threshold.

Behavioral assessments will be performed using the Coma Recovery Scale-Revised before and after the first and last session by an investigator blinded to the treatment allocation. Fifteen minutes of high-density EEG will also be recorded directly before and after the first and last stimulation session. During this same period of time, electrocardiography (EKG) will be recorded to measure parasympathetic indirect signs of vagal stimulation.

3 months after the last stimulation session, an outcome follow-up will be done, using the Glasgow Outcome Scale Extended (GOS-E) and the Disability Rating scale (DRS).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Change in CRS-R total score and index score
timeFrame: 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:
measure: Change in EEG
timeFrame: 15 min before the stimulation period and 15 min after the stimulation period.
Other outcomes:
Locations:
city: Ottignies-Louvain-la-Neuve
country: Belgium
facility: Centre Neurologique William Lennox
state: Brabant Wallon
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
Study officials:
affiliation: Université de Liège
name: Aurore Thibaut, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.