Vagal Nerve Stimulation to Treat Disorders of Consciousness
- Conditions
- Disorder of Consciousness
- Registration Number
- NCT06681168
- Lead Sponsor
- University of Milano Bicocca
- Brief Summary
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.
- Detailed Description
This is a prospective, multicentric, double-blind, parallel, 2 arms, randomized controlled trial that compares active taVNS stimulation against sham stimulation.
The primary objective of this study is 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 (DoC), including comatose patients, unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). The hypothesis is that taVNS will improve patients' behavioral scores compared to sham stimulation, as measured by an improvement of at least 3 points in the Coma Recovery Scale-Revised score (CRS-R) or an improvement in the diagnosed level of consciousness, measured at 3 months post-randomization, coinciding with the end of stimulation.
As a secondary objective, we will investigate whether:
1. taVNS is effective in achieving a faster time to recovery of consciousness in DoC patients compared to controls;
2. the CRS-R score differs in the two groups at 3 and 6 months post-randomization;
3. the persistence of improvements in the treated group also at 6 months post-randomization.
taVNS stimulation using the Parasym device or sham stimulation will be applied from the time of enrolment (between 7 to 15 days since admission in ICU) un-til day 90 post-enrolment.
Active stimulations will be carried out daily for 60 minutes twice daily during the acute phase and daily 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 prede-fined 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).
Assuming a delta of response of 30% at 3 months between the experimental and the sham group and considering a 1:1 randomization ratio and a 20% drop-out rate, a sample of 53 patients per group (106 in total) is required to reach a power of 80% (alpha=5% and two-sided test on proportion).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 106
- 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;
- availability of the device.
- 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);
- History of previous serious neurological disability before the brain injury;
- Seizures or status epilepticus as cause sustaining the disorder of consciousness;
- Patients already enrolled in another ongoing interventional trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Rate of response to stimulation 90 days post-randomization 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.
- Secondary Outcome Measures
Name Time Method taVNS effectiveness 90 days post-randomization To evaluate if taVNS is effective in achieving a faster time to recovery of consciousness in DoC patients compared to controls.
CRS-R score difference 90 days and 180 days post randomization To evaluate if the CRS-R score differs in the two groups at 3 and 6 months post-randomization.
Efficacy duration 180 days post-randomization To evaluate if improvements persist in the treated group
Trial Locations
- Locations (11)
ASST Papa Giovanni XXIII
🇮🇹Bergamo, BG, Italy
ASST degli Spedali Civili
🇮🇹Brescia, BS, Italy
ASST Lariana Ospedale S. Anna
🇮🇹Como, CO, Italy
Ospedale Policlinico San Martino IRCCS
🇮🇹Genova, GE, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, MB, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, MI, Italy
Humanitas Research Hospital
🇮🇹Rozzano, MI, Italy
Azienda Ospedale Università di Padova
🇮🇹Padova, PD, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, PR, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, RM, Italy
ASST Sette Laghi Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Virginia, Italy