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

Minimally Conscious State Clinical Trial

Official title:

Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness: a Randomized Double-blind Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04065386
• Other study ID #: 2019/91
• Status: Recruiting
• Phase: N/A
• Start date: February 9, 2022
• Est. completion date: December 2024

Study information

• Verified date: November 2022
• Source: University of Liege
• Contact: Marie Vitello, MSc
• Phone: +32 4 284 36 14
• Email: marie.vitello[@]uliege.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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)

Related Conditions & MeSH terms

• Consciousness Disorder
• Consciousness Disorders
• Disease
• Minimally Conscious State
• Persistent Vegetative State
• Vegetative State

Intervention

Device:
• Active taVNS
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.
• sham taVNS
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.

Locations

Country	Name	City	State
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Centre Neurologique William Lennox	Ottignies-Louvain-la-Neuve	Brabant Wallon

Sponsors (1)

Lead Sponsor	Collaborator
University of Liege

Country where clinical trial is conducted

Belgium, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in EEG	Improvement in cerebral activity (i.e. power spectrum in the alpha and theta band and connectivity) as measured by EEG	15 min before the stimulation period and 15 min after the stimulation period.