Vagus Nerve Stimulation in Patients in Comatose State

NCT07719595 | Recruiting FDA Device

• 2 other identifiers: IRB2019-00199 MOD061R61MH138612
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury; Severe Traumatic Brain Injury; Disorders of Consciousness Due to Severe Brain Injury; Coma, Traumatic

Keywords

taVNS; taTNS; transcutaneous auricular vagus nerve stimulation; trigeminal nerve stimulation; dual-site neuromodulation; coma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of Participants With Device- or Stimulation-Related Adverse Events

  Baseline to Day 7, or baseline to Day 28 for participants with extended treatment

Study Arms (1)

Dual-site auricular stimulation (taVNS + taTNS)

EXPERIMENTAL

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)

Interventions

Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) DEVICE

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.

Dual-site auricular stimulation (taVNS + taTNS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sima Mofakham: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries, Traumatic; Coma, Post-Head Injury; Coma

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Sima Mofakham, PhD

CONTACT

631-444-1278; sima.mofakham@stonybrookmedicine.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurosurgery

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 22, 2026
• Study Start: June 26, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 12 months after publication of the primary results and ending 5 years following publication.
• 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.

Locations

US (1)