Traumatic Brain InjuryNCT07719595
Vagus Nerve Stimulation in Patients in Comatose State
A study testing Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) in people with Traumatic Brain Injury and Severe Traumatic Brain Injury, run by Sima Mofakham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury, Severe Traumatic Brain Injury, Disorders of Consciousness Due to Severe Brain Injury
- What is being tested?
- Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2026to Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stony Brook University Hospital
Stony Brook, New York, 11794
Sima Mofakham, PhD, 631-444-1278, sima.mofakham@stonybrookmedicine.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Severe Traumatic Brain Injury, Disorders of Consciousness Due to Severe Brain Injury, Coma, Traumatic
- Being tested
- Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS)
- Keywords
- taVNS, taTNS, transcutaneous auricular vagus nerve stimulation, trigeminal nerve stimulation, dual-site neuromodulation, coma
- Medical subject headings
- Brain Injuries, Traumatic, Coma, Post-Head Injury, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Dual-site auricular stimulation (taVNS + taTNS) | Experimental | Experimental: Dual-site auricular stimulation (taVNS + taTNS). All enrolled participants receive active vagal and trigeminal auricular stimulation. Receives: Device: Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: Baseline to Day 7, or baseline to Day 28 for participants with extended treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2026
- Study start26 Jun 2026
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sima Mofakham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Sima Mofakham, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07719595
- Sponsor's protocol ID
- IRB2019-00199 MOD061
- Other IDs
- R61MH138612
- Status last verified
- Jun 2026
- First submitted
- 26 Jun 2026
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) for Disorders of Consciousness After Traumatic Brain Injury: A Pilot Efficacy Study
- ClinicalTrials.gov ID
- NCT07719595
- Acronym / sponsor ID
- IRB2019-00199 MOD061
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Sima MofakhamUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 26 Jun 2026 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 22 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dual-site auricular stimulation (taVNS + taTNS) | Experimental | Device: Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS)Experimental: Dual-site auricular stimulation (taVNS + taTNS). All enrolled participants receive active vagal and trigeminal auricular stimulation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Dual-site auricular stimulation (taVNS + taTNS) |
Primary outcome
Change in Coma Recovery Scale-Revised (CRS-R) Total Score
Time frame: 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
Time frame: 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.
1 secondary outcome
Number of Participants With Device- or Stimulation-Related Adverse Events
Time frame: Baseline to Day 7, or baseline to Day 28 for participants with extended treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dual-Site Transcutaneous Auricular Nerve Stimulation (taVNS + taTNS) in people with Traumatic Brain Injury and Severe Traumatic Brain Injury, run by Sima Mofakham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sima Mofakham, PhD (631-444-1278, sima.mofakham@stonybrookmedicine.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Coma Recovery Scale-Revised (CRS-R) Total Score (time frame: Baseline to Day 7, or baseline to Day 28 for participants with extended treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.