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

November 14, 2022 updated by: Aurore Thibaut, University of Liege

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

48

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Liège, Belgium, 4000
        • Recruiting
        • Centre Hospitalier Universitaire de Liège
        • Contact:
        • Contact:
    • Brabant Wallon
      • Ottignies-Louvain-la-Neuve, Brabant Wallon, Belgium, 1340

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Active taVNS

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
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.
PLACEBO_COMPARATOR: Sham taVNS

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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CRS-R total score and index score
Time Frame: 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).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in EEG
Time Frame: 15 min before the stimulation period and 15 min after the stimulation period.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Liege

Investigators

  • Principal Investigator: Aurore Thibaut, PhD, Université de Liège

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 9, 2022

Primary Completion (ANTICIPATED)

June 1, 2024

Study Completion (ANTICIPATED)

December 1, 2024

Study Registration Dates

First Submitted

August 21, 2019

First Submitted That Met QC Criteria

August 21, 2019

First Posted (ACTUAL)

August 22, 2019

Study Record Updates

Last Update Posted (ACTUAL)

November 15, 2022

Last Update Submitted That Met QC Criteria

November 14, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019/91

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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