search
Back to results

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

Primary Purpose

Consciousness Disorder, Minimally Conscious State, Vegetative State

Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Active taVNS
sham taVNS
Sponsored by
University of Liege
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Consciousness Disorder focused on measuring 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

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Centre Neurologique William Lennox
  • Centre Hospitalier Universitaire de LiègeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active taVNS

Sham taVNS

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in EEG
Improvement in cerebral activity (i.e. power spectrum in the alpha and theta band and connectivity) as measured by EEG

Full Information

First Posted
August 21, 2019
Last Updated
November 14, 2022
Sponsor
University of Liege
search

1. Study Identification

Unique Protocol Identification Number
NCT04065386
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 9, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Liege

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active taVNS
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sham taVNS
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active taVNS
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
sham taVNS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in CRS-R total score and index score
Description
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.
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).
Secondary Outcome Measure Information:
Title
Change in EEG
Description
Improvement in cerebral activity (i.e. power spectrum in the alpha and theta band and connectivity) as measured by EEG
Time Frame
15 min before the stimulation period and 15 min after the stimulation period.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marie Vitello, MSc
Phone
+32 4 284 36 14
Email
marie.vitello@uliege.be
First Name & Middle Initial & Last Name or Official Title & Degree
Aurore Thibaut, PhD
Phone
+32 4 284 36 12
Email
athibaut@uliege.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aurore Thibaut, PhD
Organizational Affiliation
Université de Liège
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Neurologique William Lennox
City
Ottignies-Louvain-la-Neuve
State/Province
Brabant Wallon
ZIP/Postal Code
1340
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas Lejeune, PhD
Email
nicolas.lejeune@uliege.be
Facility Name
Centre Hospitalier Universitaire de Liège
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Vitello, MSc
Phone
+32 4 284 36 14
Email
marie.vitello@uliege.be
First Name & Middle Initial & Last Name & Degree
Aurore Thibaut, PhD
Phone
+32 4 284 36 12
Email
athibaut@uliege.be

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28017322
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.
Results Reference
background
PubMed Identifier
27898202
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs