Vagal Nerve Stimulation to Treat Disorders of Consciousness
ConditionDisorder of Consciousness
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorFondazione IRCCS San Gerardo dei Tintori
About this trial
This interventional study aims to assess the clinical efficacy of transcutaneous auricular vagal nerve stimulation (taVNS) against sham stimulation on the recovery of consciousness in patients with disorders of consciousness. The main question it aims to answer is: will taVNS improve patients' behavioral scores or will it produce an improvement in the diagnosed level of consciousness? Researchers will compare the results with non-stimulated unconscious patients to see if the re-gain of consciousness is faster in the treated group.
Participants will undergo taVNS stimulation using the Parasym device or sham stimulation will be applied from the time of enrolment.
Active stimulations will be carried out for 60 minutes twice daily during the acute phase and daily during the rehabilitation phase.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years old;
any acquired cerebral damage of any known etiology;
diagnosis of coma, UWS, or MCS with the corresponding basal CRS-R (Coma Recovery Scale-Revised) score performed during the screening period from 7 to 15 days since admission in ICU;
intact ear skin;
Disqualifiers
Patients with severe hemodynamic, respiratory, infectious, or neurological instability requiring active treatment requiring mechanical ventilation or vasoactive drugs or pending acute neurosurgical interventions;
Need for deep sedation, including general anesthetics (e.g., propofol) or a combination of central-acting sedatives;
Documented pregnancy;
Active implant (e.g., pacemaker, cochlear implant);
Trial design
Design model
Parallel
Treatments tested in this trial
stimulated group
DeviceParticipants will be randomly assigned to receive either taVNS applied to the tragus of the ear or a sham stimulation from the time of randomization for 90 days. Active simulations will be carried out daily using the Parasym device for 60 minutes twice daily during the acute phase (two sessions, one in the morning and one in the afternoon), and once daily (single session) during the rehabilitation phase. The stimulation waveform includes trains of pulses with widths of 200 µs and repetition rate of 20 Hz (Nurosym proprietary waveform); current delivery will be set at a predefined therapeutic level below 0.25 W/cm² (Watts per centimeter squared), that being the defined risk threshold for a thermal burn. The device adjusts stimulation intensity at 0.8 mA steps; the starting intensity will be set at 16 mA (level 20).
Sham (No Treatment)
DeviceThe sham stimulation involves placing the electrode on the same site without delivering any electrical current. The device will be applied to the tragus without electrical current delivered from the time of randomization for 90 days (i.e., the time of randomization coincides with the first stimulation session).
Treatment groups
106 Participants
are divided into 2 treatment groupsGroup A: Stimulated groupExperimental treatment 1 intervention
Group B: Control groupSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Rate of response to stimulation
A response is defined as an increase of at least 3 points in the Coma Recovery Scale-Revised (CRS-R), or a clinical change in the diagnosed level of consciousness: from coma to unresponsive wakefulness syndrome (UWS), from UWS to minimally conscious state (MCS), or emergence from MCS. Clinical markers for the diagnostic improvements are derived from the CRS-R scale: • The transition from coma to UWS will be defined as the appearance of eyes opening. • The MCS minus state will be defined by the appearance of visual pursuit, object localization, automatic motor responses, or object manipulation. • The MCS plus will be defined by the appearance of non-functional intentional communication, intelligible verbalization, object recognition, or movement to command. • Emergence from MCS will be defined by the appearance of functional accurate communication or functional object use.
Time frame
90 days post-randomizationSecondary outcomes
1
taVNS efficacy in speeding the time of recovery from the disorder of consciousness
To evaluate whether taVNS is effective in achieving a faster time to recovery of consciousness in DoC patients compared to controls.
Time frame
90 days post-randomization2
CRS-R score difference
To evaluate if the coma recovery scale revised score (CRS-R) differs in the two groups at 3 and 6 months post-randomization. The CRS-R scale is a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness, and is intended to be used to establish diagnosis, monitor behavioral recovery, predict outcome, and assess treatment effectiveness. It consists of 6 subscales designed to assess auditory function, receptive and expressive language, visuoperception, communication ability, motor functions, and arousal level. Minimum score: 0 - Maximum score: 23. While the CRS-R total score should not be relied upon to establish a diagnosis, a total score of 10 or greater indicates a diagnosis of MCS or eMCS. The CRS-R can also be used to differentiate patients into "MCS+" and "MCS-" subgroups, based on the presence or absence of receptive or expressive language function.
Time frame
90 days and 180 days post randomization3
Efficacy duration
To evaluate if improvements persist in the treated group
Time frame
180 days post-randomizationOther outcomes
1
Responders phenotype
To evaluate the phenotype of clinical responders by identifying factors after stratification of patients by clinical diagnosis (different etiology, such as traumatic brain injury, subarachnoid hemorrhage, versus intracranial hemorrhage, or ischemic/hemorrhagic stroke).
Time frame
180 daysSponsors and contacts
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Source ClinicalTrials.gov
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