Vagus Nerve Stimulation in Patients in Comatose State

Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) for Disorders of Consciousness After Traumatic Brain Injury: A Pilot Efficacy Study

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.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury; Severe Traumatic Brain Injury; Disorders of Consciousness Due to Severe Brain Injury; Coma, Traumatic
• Intervention / Treatment: Device: Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS)

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sima Mofakham, PhD; Phone Number: 631-444-1278; Email: sima.mofakham@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Hospital
      • Contact: Sima Mofakham, PhD; Phone Number: 631-444-1278; Email: sima.mofakham@stonybrookmedicine.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dual-site auricular stimulation (taVNS + taTNS); Experimental: Dual-site auricular stimulation (taVNS + taTNS). All enrolled participants receive active vagal and trigeminal auricular stimulation.

Device: Dual-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Coma Recovery Scale-Revised (CRS-R) Total Score	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.	Baseline to Day 7, or baseline to Day 28 for participants with extended treatment
Change in SeeMe-Detected Stimulus-Evoked Voluntary Motor Responses	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.	Baseline to Day 7, or baseline to Day 28 for participants with extended treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Device- or Stimulation-Related Adverse Events	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.	Baseline to Day 7, or baseline to Day 28 for participants with extended treatment

Collaborators and Investigators

• Sponsor: Sima Mofakham
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: transcutaneous auricular vagus nerve stimulation; trigeminal nerve stimulation; coma; taVNS; taTNS; dual-site neuromodulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurobehavioral Manifestations; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Consciousness Disorders; Unconsciousness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries, Traumatic; Coma; Coma, Post-Head Injury
• Other Study ID Numbers: IRB2019-00199 MOD061; R61MH138612 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying published results will be shared, including CRS-R scores, SeeMe-derived movement metrics, stimulation parameters, and safety data. Data will be available following publication of the primary results. Requests will be reviewed by the study team and require a data use agreement and confirmation of appropriate IRB or ethics approval. Raw facial video will not be shared due to the inherent re-identifiability of facial imagery; derived quantitative movement features will be shared instead.
• IPD Sharing Time Frame: Beginning 12 months after publication of the primary results and ending 5 years following publication.
• IPD Sharing Access Criteria: Access will be granted to qualified investigators whose proposed use has been approved by the study team. Requestors must submit a methodologically sound research proposal and a signed data use agreement, and must provide documentation of IRB or equivalent ethics approval for the proposed analysis. Approved requestors will receive de-identified individual participant data, including CRS-R scores, SeeMe-derived quantitative movement metrics, stimulation parameters, and safety data, together with the study protocol, statistical analysis plan, and blank informed consent form. Raw facial video will not be released due to the inherent re-identifiability of facial imagery. Requests should be directed to the principal investigator at sima.mofakham@stonybrookmedicine.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No