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Vagal Nerve Stimulation in Coma Patients (SNV)

Primary Purpose

Chronic Consciousness Disorders, Vegetative State, Minimally Conscious State

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
stimulation device
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Chronic Consciousness Disorders focused on measuring Vagus nerve stimulation, vegetative state, minimally conscious state, akinetic mutism, consciousness, connectivity

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged between 18 and 60 years old
  • Patients with history of cranial trauma, cerebrovascular accident, or other event leading to cerebral anoxia, suffering of chronic alteration of consciousness (Vegetative State, Minimally Conscious State, akinetic mutism). The diagnostic will be based on clinical scales
  • Patients already having a neurophysiologic checkup (EEG)
  • Patients breathing without invasive help, and who are in a stable medical state
  • Patients with a history of disease of at least 6 months
  • Patients without clinical evolution for several months
  • Patients with social security
  • Patients for whom a family member have signed a written consent

Exclusion Criteria:

  • Patients with tracheotomy
  • Pregnant women
  • Intubated patients
  • Patients with damaged vagus nerves
  • Patients with pre existing neurological conditions other than the one responsible for the consciousness disorder
  • Patients with medical complications
  • Patients suffering of septic infection
  • Patients with a significant dysphagia
  • Patients with dyspnea or shortness of breath
  • Patients with obstructive sleep apnea
  • Patients with any conditions non authorized by the stimulating device manufacturer (Cyberonics)

Sites / Locations

  • Hôpital Neurologique de Lyon Pierre WertheimerRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients will undergo the same procedure

Arm Description

Outcomes

Primary Outcome Measures

Change over time of clinical scores on the Coma Recovery Scale - Revised
The primary outcome will be the change over time of patients' clinical state. Investigators will employ a widely used scale: Coma Recovery Scale - Revised. Patients will be evaluated by the same trained doctor. Results will be analyzed using a within subject design, each patients will be his own control. Investigators predict a progressive improvement after the onset of treatment, compared to the two pre-stimulation evaluations.

Secondary Outcome Measures

Evaluation of brain activity changes using EEG
EEG will allow investigators to monitor brain activity at rest as well as in response to various sensory stimuli. Investigators will measure changes in evoked potentials, source of activity and frequency power known to be altered in coma patients. In addition EEG will offer the opportunity to record brain activity while the stimulating device is on.
MRI (anisotropy and fibers density) evaluation of anatomo-connectivity changes
Investigators will use Diffusion Tensor Imaging (DTI) before and after VNS to evaluate anisotropy and anatomical connectivity between brain stem, thalamus and various cortical areas, especially regarding the thalamo-cortical loops. During the MRI exams the stimulation device will be turned off for safety reasons.
fMRI evaluation of bold signal resting state activity and functional connectivity changes
WInvestigators will perform resting state analysis of bold signal and functional connectivity to quantify reactivation of brain region after VNS and inter region communication, especially regarding the thalamo-cortical loops. During the fMRI exams the stimulation device will be turned off for safety reasons.
PET scan evaluation of brain metabolism (Glucose consumption) changes
Investigators will use the radioligand Fluorodesoxyglucose [18F-FDG] to assess brain consumption of glucose. This measure is complementary to the one provided by fMRI and has already been used in coma patients. Moreover, thanks to a hybrid MRI/PET scanner, investigators will perform the two exams simultaneously to correlate these two measures in real time.
Monitoring heart rate variability
Investigators hypothesize that VNS will modulate several physiological parameters, among those Heart Rate Variability, a marker of the balance between sympathetic and parasympathetic activity. Investigators will measure changes of high frequencies / low frequencies ratio.
: Monitoring changes of serum free serotonin concentration
Vagus nerve is known to stimulate raphe nuclei, the region of serotonin synthesis. Investigators hypothesize that VNS will increase serum free serotonin concentration. Investigators will measure it using high performance liquid chromatography, and report the changes of values of serotonin concentration.
Monitoring changes of thermal reaction to emotional stimuli
Investigators will use regulation of facial temperature as an index of consciousness. When humans react to emotions, the temperature of their face changes. This regulation is dependent on consciousness state, and therefore should vary across time in this protocol. Investigators will measure changes in temperature (°Celsius) of patients' face throughout the task.

Full Information

First Posted
October 6, 2015
Last Updated
November 21, 2019
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02591069
Brief Title
Vagal Nerve Stimulation in Coma Patients
Acronym
SNV
Official Title
Vagus Nerve Stimulation in Patients With Chronic Consciousness Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 2015 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Minimally Conscious (MCS) or Vegetative State (VS) are disorders of consciousness which often occur following traumatic brain injury or ischemia. These alterations result most of the time in patients' loss of autonomy and require long years of special care. No efficient therapy to improve patients' consciousness has been found so far. Investigators propose to use vagal nerve stimulation (VNS) to restore cortical activity and patients' embodied self. The investigators' main hypothesis is that VNS will reestablish the thalamo-cortical connectivity leading to an improvement of the consciousness state. To test this hypothesis, investigators will use behavioral measures as well as fMRI, PET scan and EEG to assess brain activity. Patients will be evaluated before and during eight months following implantation of the stimulation device.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Consciousness Disorders, Vegetative State, Minimally Conscious State, Akinetic Mutism
Keywords
Vagus nerve stimulation, vegetative state, minimally conscious state, akinetic mutism, consciousness, connectivity

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
All patients will undergo the same procedure
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
stimulation device
Intervention Description
All patients included in the study will undergo baseline assessment of all measures before surgery (implantation of a vagus nerve stimulation device). A second baseline assessment will take place after surgery, before the beginning of the stimulation. Stimulation intensity will start at 0.25mA and increase progressively by 0.25mA each week until reaching 1mA. Then, intensity will be set at 1.5mA (recommended by manufacturer) and will stay to this level until the end of the trial. Experimenters will keep the right to modify these parameters depending on patients' reaction to the treatment.
Primary Outcome Measure Information:
Title
Change over time of clinical scores on the Coma Recovery Scale - Revised
Description
The primary outcome will be the change over time of patients' clinical state. Investigators will employ a widely used scale: Coma Recovery Scale - Revised. Patients will be evaluated by the same trained doctor. Results will be analyzed using a within subject design, each patients will be his own control. Investigators predict a progressive improvement after the onset of treatment, compared to the two pre-stimulation evaluations.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation, then once per week for a month starting one week after the beginning of stimulation; then once a month for 6 months.
Secondary Outcome Measure Information:
Title
Evaluation of brain activity changes using EEG
Description
EEG will allow investigators to monitor brain activity at rest as well as in response to various sensory stimuli. Investigators will measure changes in evoked potentials, source of activity and frequency power known to be altered in coma patients. In addition EEG will offer the opportunity to record brain activity while the stimulating device is on.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation, then once per week for a month starting one week after the beginning of stimulation, then once a month for 6 months.
Title
MRI (anisotropy and fibers density) evaluation of anatomo-connectivity changes
Description
Investigators will use Diffusion Tensor Imaging (DTI) before and after VNS to evaluate anisotropy and anatomical connectivity between brain stem, thalamus and various cortical areas, especially regarding the thalamo-cortical loops. During the MRI exams the stimulation device will be turned off for safety reasons.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation and then one, three and six months after the onset of stimulation.
Title
fMRI evaluation of bold signal resting state activity and functional connectivity changes
Description
WInvestigators will perform resting state analysis of bold signal and functional connectivity to quantify reactivation of brain region after VNS and inter region communication, especially regarding the thalamo-cortical loops. During the fMRI exams the stimulation device will be turned off for safety reasons.
Time Frame
Firsts First assessment one week before implantation second assessment 3 weeks after implantation,, and then one, three and six months after the onset of stimulation.
Title
PET scan evaluation of brain metabolism (Glucose consumption) changes
Description
Investigators will use the radioligand Fluorodesoxyglucose [18F-FDG] to assess brain consumption of glucose. This measure is complementary to the one provided by fMRI and has already been used in coma patients. Moreover, thanks to a hybrid MRI/PET scanner, investigators will perform the two exams simultaneously to correlate these two measures in real time.
Time Frame
One baseline assessment one week before stimulation and a second one after 3 months of stimulation.
Title
Monitoring heart rate variability
Description
Investigators hypothesize that VNS will modulate several physiological parameters, among those Heart Rate Variability, a marker of the balance between sympathetic and parasympathetic activity. Investigators will measure changes of high frequencies / low frequencies ratio.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation, then once per week for a month starting one week after the beginning of stimulation, then once a month for 6 months.
Title
: Monitoring changes of serum free serotonin concentration
Description
Vagus nerve is known to stimulate raphe nuclei, the region of serotonin synthesis. Investigators hypothesize that VNS will increase serum free serotonin concentration. Investigators will measure it using high performance liquid chromatography, and report the changes of values of serotonin concentration.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation, then once per week for a month starting one week after the beginning of stimulation, then once a month for 6 months.
Title
Monitoring changes of thermal reaction to emotional stimuli
Description
Investigators will use regulation of facial temperature as an index of consciousness. When humans react to emotions, the temperature of their face changes. This regulation is dependent on consciousness state, and therefore should vary across time in this protocol. Investigators will measure changes in temperature (°Celsius) of patients' face throughout the task.
Time Frame
First assessment one week before implantation second assessment 3 weeks after implantation, then once per week for a month starting one week after the beginning of stimulation, then once a month for 6 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged between 18 and 60 years old Patients with history of cranial trauma, cerebrovascular accident, or other event leading to cerebral anoxia, suffering of chronic alteration of consciousness (Vegetative State, Minimally Conscious State, akinetic mutism). The diagnostic will be based on clinical scales Patients already having a neurophysiologic checkup (EEG) Patients breathing without invasive help, and who are in a stable medical state Patients with a history of disease of at least 6 months Patients without clinical evolution for several months Patients with social security Patients for whom a family member have signed a written consent Exclusion Criteria: Patients with tracheotomy Pregnant women Intubated patients Patients with damaged vagus nerves Patients with pre existing neurological conditions other than the one responsible for the consciousness disorder Patients with medical complications Patients suffering of septic infection Patients with a significant dysphagia Patients with dyspnea or shortness of breath Patients with obstructive sleep apnea Patients with any conditions non authorized by the stimulating device manufacturer (Cyberonics)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angela Sirigu, PhD
Phone
04 37 91 12 31
Email
sirigu@isc.cnrs.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jacques Luauté, Pr
Phone
04 72 35 78 95
Email
jacques.luaute@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques Luauté, Pr
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Neurologique de Lyon Pierre Wertheimer
City
Bron
ZIP/Postal Code
69500
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacques Luauté, MD
Phone
4 72 35 78 95
Ext
0033
Email
jacques.luaute@chu-lyon.fr

12. IPD Sharing Statement

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Vagal Nerve Stimulation in Coma Patients

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