Chronic Consciousness DisordersSNVNCT02591069
Vagal Nerve Stimulation in Coma Patients
A study testing stimulation device in people with Chronic Consciousness Disorders and Vegetative State, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic Consciousness Disorders, Vegetative State, Minimally Conscious State
- What is being tested?
- stimulation device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2015to Jan 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Neurologique de Lyon Pierre Wertheimer
Bron, 69500
Jacques Luauté, MD, 4 72 35 78 95 ext. 0033, jacques.luaute@chu-lyon.fr
About this study
Official title: Vagus Nerve Stimulation in Patients With Chronic Consciousness Disorders
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.
- Conditions
- Chronic Consciousness Disorders, Vegetative State, Minimally Conscious State, Akinetic Mutism
- Being tested
- stimulation device
- Keywords
- Vagus nerve stimulation, vegetative state, minimally conscious state, akinetic mutism, consciousness, connectivity
- Medical subject headings
- Persistent Vegetative State, Akinetic Mutism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stimulation deviceDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| All patients will undergo the same procedure | Experimental | Not described Receives: Device: stimulation device |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (7)
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.
Measured: 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.
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.
Measured: First assessment one week before implantation second assessment 3 weeks after implantation and then one, three and six months after the onset of stimulation.
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.
Measured: 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.
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.
Measured: One baseline assessment one week before stimulation and a second one after 3 months of stimulation.
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.
Measured: 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.
: 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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2015 (estimated)
- Study startOct 2015
- Primary completionJan 2016
- Study completionJan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Consciousness DisordersStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jacques Luauté, Pr, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02591069
- Sponsor's protocol ID
- 2013-833
- Other IDs
- 2014-A00125-42
- Acronym
- SNV
- Status last verified
- Nov 2019
- First submitted
- 6 Oct 2015
- Last updated
- 25 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vagus Nerve Stimulation in Patients With Chronic Consciousness Disorders
- ClinicalTrials.gov ID
- NCT02591069
- Acronym / sponsor ID
- SNV / 2013-833
- Conditions
- Chronic Consciousness Disorders, Vegetative State, Minimally Conscious State, Akinetic Mutism
- Keywords
- Vagus nerve stimulation, vegetative state, minimally conscious state, akinetic mutism, consciousness, connectivity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2021 (estimated)
- First posted
- 29 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients will undergo the same procedure | Experimental | Device: stimulation device |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stimulation deviceAll 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. | Device | All patients will undergo the same procedure |
Primary outcome
Change over time of clinical scores on the Coma Recovery Scale - Revised
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.
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.
7 secondary outcomes
Evaluation of brain activity changes using EEG
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.
MRI (anisotropy and fibers density) evaluation of anatomo-connectivity changes
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.
fMRI evaluation of bold signal resting state activity and functional connectivity changes
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.
PET scan evaluation of brain metabolism (Glucose consumption) changes
Time frame: One baseline assessment one week before stimulation and a second one after 3 months of stimulation.
Monitoring heart rate variability
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.
: Monitoring changes of serum free 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.
Monitoring changes of thermal reaction to emotional stimuli
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacques Luauté, Pr principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing stimulation device in people with Chronic Consciousness Disorders and Vegetative State, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Angela Sirigu, PhD (04 37 91 12 31, sirigu@isc.cnrs.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change over time of clinical scores on the Coma Recovery Scale - Revised (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019.