Coma, Traumatic, Disorders of Consciousness Due to Severe Brain Injury, Severe Traumatic Brain Injury, Traumatic Brain Injury
Conditions
Keywords
taVNS, taTNS, transcutaneous auricular vagus nerve stimulation, trigeminal nerve stimulation, dual-site neuromodulation, coma
Brief summary
Some patients with severe traumatic brain injury cannot respond at the bedside, yet about 1 in 4 may be aware but unable to show it - a hidden state called cognitive motor dissociation. This study tests a gentle, non-invasive treatment delivered through clips on the left ear that stimulates two nerves at once: the vagus nerve at the inner ear (taVNS) and the trigeminal nerve at the outer ear (taTNS). Each nerve has separately been shown to help people with disorders of consciousness recover, but they have not been combined before. All enrolled patients receive the stimulation for one hour a day, with continuous heart and oxygen monitoring and a pain-protection check used to keep the dose safe. The study measures recovery two ways: the Coma Recovery Scale-Revised (CRS-R), scored by clinicians, and SeeMe, an automated camera system that detects tiny command-driven movements the eye cannot see.
Detailed description
This prospective, single-center, open-label, single-arm pilot study enrolls a subcohort of comatose TBI patients from the parent SeeMe study (NCT07560631) whose legally authorized representative consents to a stimulation addendum. Dual-site transcutaneous auricular nerve stimulation is delivered to the left ear: the vagal site (cymba conchae) targets the auricular branch of the vagus nerve, and the trigeminal site (outer ear) targets the auriculotemporal branch - each with distinct, optimized parameters. Mechanistically, vagal afferents project to the nucleus tractus solitarius and the ascending reticular activating system to promote arousal, while trigeminal afferents project via the spinal trigeminal nucleus to thalamus and cortex to enhance thalamocortical connectivity; the dual-site paradigm aims to drive the cortico-striatal-thalamic-cortical loop from two convergent directions. Baseline assessment captures CRS-R, GCS, vital signs, NCS-R, heart-rate variability, and EEG. Daily one-hour sessions include pre/post vitals, NCS-R-guided titration, continuous telemetry, ear-site inspection, and daily CRS-R. In parallel, the SeeMe computer-vision platform quantifies stimulus-evoked facial and hand movements. The course runs 7 consecutive days, extendable to 28 days. Findings will inform a future sham-controlled randomized trial and closed-loop integration with SeeMe.
Interventions
DEVICEDual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS)
DEVICE: Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS). Delivered via ear-clip electrodes on the LEFT ear using the Sparrow Ascent / Sparrow Link tAN System (Spark Biomedical; FDA-cleared K230796), operated as an NSR investigational device. Vagal site (inner ear / cymba conchae): 15 Hz, 250 µs pulse width, 3 mA fixed, duty cycle 5 min on / 10 s off. Trigeminal site (outer ear): 100 Hz, 250 µs pulse width, 3 mA fixed, duty cycle 5 min on / 10 s off. Session: 1 hour/day. Course: 7 consecutive days, extendable to 28 days. Intensity titrated with the Nociception Coma Scale-Revised (NCS-R): step down 0.5 mA if NCS-R \> 4/9, SpO2 ≤ 95%, or HR rises ≥ 20 bpm; continuous cardiac/hemodynamic monitoring with prespecified stopping rules.
Sponsors
Sima Mofakham
National Institute of Mental Health (NIMH)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), or minimally conscious state (MCS) as determined by baseline CRS-R * Acute traumatic brain injury with documented intracranial pathology on neuroimaging * Admission to the Neurology or Neurosurgical ICU * Legally authorized representative (LAR) available and willing to consent, including the Stimulation Addendum Consent Form
Exclusion criteria
* Implanted cardiac pacemaker, vagus nerve stimulator, or other active implanted device * Known cardiac arrhythmia (e.g., 2nd-/3rd-degree AV block, atrial fibrillation with uncontrolled rate) * Active seizures not controlled by current antiepileptic regimen * Skin breakdown, infection, or anatomical abnormality of the left ear precluding electrode placement * Pregnancy * Hemodynamic instability requiring vasopressor escalation at the time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Coma Recovery Scale-Revised (CRS-R) Total Score | Baseline to Day 7, or baseline to Day 28 for participants with extended treatment | Change in level of consciousness will be assessed using the Coma Recovery Scale-Revised total score. The outcome will be reported as the within-participant change in total score from baseline to the end of treatment, as scored by a trained assessor. Scores range from 0 to 23, with higher scores indicating better neurobehavioral function and greater recovery of consciousness. |
| Change in SeeMe-Detected Stimulus-Evoked Voluntary Motor Responses | Baseline to Day 7, or baseline to Day 28 for participants with extended treatment | Change in command-evoked voluntary motor responses will be assessed using the SeeMe automated camera-based detection system. The outcome will be reported as the within-participant change in the percentage of command trials with SeeMe-positive responses from baseline to the end of treatment. Scores range from 0% to 100%, with higher percentages indicating more frequent command-evoked voluntary motor responses. A SeeMe-positive response is defined as a Kolmogorov-Smirnov statistic greater than 0.1 and pixel displacement greater than 400, detected reliably in at least 3 of 10 command trials. SeeMe scoring will be automated and performed blinded to stimulation timing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Device- or Stimulation-Related Adverse Events | Baseline to Day 7, or baseline to Day 28 for participants with extended treatment | Adverse events attributed to auricular stimulation will be recorded and graded using CTCAE v5.0, including ear-site skin reactions, bradycardia or other arrhythmia, oxygen desaturation, and hemodynamic instability. Events requiring NCS-R-guided dose reduction or meeting prespecified stopping criteria will be reported. |
Countries
United States
Contacts
CONTACTSima Mofakham, PhD
Outcome results
None listed