Vagal Nerve Stimulation in Coma Patients

Minimally Conscious State Clinical Trial

— SNV  

Official title:

Vagus Nerve Stimulation in Patients With Chronic Consciousness Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02591069
• Other study ID #: 2013-833
• Secondary ID: 2014-A00125-42
• Status: Recruiting
• Phase: N/A
• Start date: October 2015
• Est. completion date: January 2021

Study information

• Verified date: November 2019
• Source: Hospices Civils de Lyon
• Contact: Angela Sirigu, PhD
• Phone: 04 37 91 12 31
• Email: sirigu[@]isc.cnrs.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4
• Est. completion date: January 2021
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Akinetic Mutism
• Chronic Consciousness Disorders
• Consciousness Disorders
• Minimally Conscious State
• Mutism
• Persistent Vegetative State
• Vegetative State

Intervention

Device:
• stimulation device
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.

Locations

Country	Name	City	State
France	Hôpital Neurologique de Lyon Pierre Wertheimer	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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	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.	First assessment one week before implantation second assessment 3 weeks after implantation and then one, three and six months after the onset of stimulation.
Secondary	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.	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.
Secondary	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.	One baseline assessment one week before stimulation and a second one after 3 months of stimulation.
Secondary	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.	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	: 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.	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	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.	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.