taVNS for Pupillary Response

Overseen By Mario Svirsky, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Disqualifiers: Cardiomyopathies, Arrhythmias, Implantable devices, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how transcutaneous auricular vagal nerve stimulation (taVNS) affects the eye's pupil response and learning. Researchers will compare taVNS to two sham treatments and no treatment to assess its impact on tasks requiring attention and learning. The trial seeks healthy individuals aged 18 to 65 with normal hearing and no heart issues or metal implants. The study aims to determine if taVNS could aid focus and learning by monitoring changes in pupils and brain activity. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on enhancing focus and learning.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that transcutaneous auricular vagal nerve stimulation (taVNS) is safe?

Research has shown that transcutaneous auricular vagal nerve stimulation (taVNS) is generally safe. Studies have found it to be well-tolerated, with only mild side effects such as skin irritation, headaches, and mild throat and nasal inflammation. One study highlighted that taVNS is a non-invasive and less risky alternative to surgery. Overall, evidence suggests that taVNS is a safe treatment with minimal side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) because it offers a non-invasive approach to potentially influence pupillary response by targeting the vagus nerve through the ear. Unlike traditional treatments that might rely on medications or more invasive procedures, taVNS uses a gentle electrical stimulation that can be applied externally. This method is promising because it could offer a safer, more convenient alternative with fewer side effects, enhancing patient comfort and accessibility. By stimulating the vagus nerve, taVNS taps into a unique mechanism that could lead to new insights into autonomic nervous system functions, sparking interest in both clinical and research settings.

What evidence suggests that transcutaneous auricular vagal nerve stimulation (taVNS) is effective for influencing pupillary response?

Research has shown that transcutaneous auricular vagal nerve stimulation (taVNS), which participants in this trial may receive, can enlarge pupils, particularly with pulsed stimulation. Several studies have found that taVNS causes noticeable pupil enlargement, similar to results seen in animal studies using a more invasive method. One study discovered that taVNS increased pupil size when applied at specific strengths. Another study found that taVNS not only enlarged pupils but also altered brain activity, improving certain brain wave patterns. These findings suggest that taVNS could affect bodily responses, prompting further exploration in this study. ^{4 6 7 8 9}

Who Is on the Research Team?

Mario Svirsky, PhD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18 to 65 with normal hearing. It's not suitable for those with heart muscle diseases, irregular heartbeats, implanted devices like pacemakers or vagal stimulators, metallic implants in their body, or pregnant women.

Inclusion Criteria

Normal audiometric testing

Exclusion Criteria

Presence of metallic implants

Pregnancy

I have heart conditions like cardiomyopathy or irregular heartbeats.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous auricular vagal nerve stimulation (taVNS) or sham during a passive task and a go/no-go task to evaluate perceptual learning and pupillary response over three sessions

3 months

3 sessions

Follow-up

Participants are monitored for changes in speed of learning and pupillary response after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham Stimulation
• Transcutaneous Auricular Vagal Nerve Stimulation (taVNS)

Trial Overview The study is testing the effects of transcutaneous auricular vagal nerve stimulation (taVNS) on how the pupil responds and on learning during a task that requires quick decisions. Participants will be compared across three groups: taVNS, sham (fake) stimulation, and no intervention.

How Is the Trial Designed?

Group I: Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) Experimental Treatment 1 Intervention

Group II: No Intervention (Control) Active Control 1 Intervention

Group III: Sham Placebo Group 1 Intervention

Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) is already approved in European Union, United States for the following indications:

Approved in European Union as taVNS for:

• Epilepsy
• Depression
• Chronic Pain
• Anxiety

Approved in United States as taVNS for:

• Depression
• Anxiety

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) using specific parameters (500μs pulse width at 10Hz and 25Hz) was found to significantly decrease heart rate (HR) in healthy individuals, indicating its potential efficacy in modulating HR.

The study demonstrated that taVNS is safe, with no adverse effects reported, and it effectively attenuated sympathetic HR rebound after stimulation, suggesting a beneficial impact on autonomic regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Badran, BW., Mithoefer, OJ., Summer, CE., et al.[2020]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) can induce significant pupil dilation in healthy subjects, particularly at a stimulation intensity of 2 mA under scotopic lighting conditions.

The study highlights that the effects of taVNS are influenced by specific stimulation parameters and the experimental setup, indicating the need for careful consideration in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcutaneous auricular vagal nerve stimulation on pupil size. Capone, F., Motolese, F., Di Zazzo, A., et al.[2021]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

In a study with 66 healthy participants, transcutaneous auricular vagus nerve stimulation (taVNS) did not significantly affect markers of noradrenergic activity, despite expectations that it would enhance this activity.

The results indicated that continuous taVNS stimulation at the tested parameters was ineffective in modulating both phasic and tonic noradrenergic responses, suggesting that this method may not be a viable approach for increasing noradrenergic activity through vagal pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity. D'Agostini, M., Burger, AM., Villca Ponce, G., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000245

Does transcutaneous auricular vagus nerve stimulation ... The meta-analysis provides strong evidence that tVNS increases pupil size only with pulsed stimulation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11866280/

Three Hundred Hertz Transcutaneous Auricular Vagus Nerve ... Active taVNS increased pupil size during stimulation for participants who received taVNS between 2 and approximately 4.8 mA, but not for participants who ...

3. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1549167/full

Effects of off-line auricular transcutaneous vagus nerve ... In our experiment we found that real taVNS slightly but significantly increased pupil size at all span lengths, with larger effects for longer ...

4. nature.com nature.com/articles/s41598-024-72179-4

Evaluating phasic transcutaneous vagus nerve stimulation ... Phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals.

5. jneurosci.org jneurosci.org/content/43/36/6306

Phasic, Event-Related Transcutaneous Auricular Vagus ... During the PLRT, active taVNS reduced and delayed pupil constriction. In the MEG, taVNS increased frontal-midline theta and alpha power during ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11841445/

A pooled analysis of the side effects of non-invasive ... (2018) concluded that taVNS is generally well-tolerated with mild side effects like skin irritation, headaches, and nasopharyngitis. However, ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2828072

Transcutaneous Auricular Vagus Nerve Stimulation for ... This randomized clinical trial investigates the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia.

8. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(24)00028-7/fulltext

Tonic and phasic transcutaneous auricular vagus nerve ... Active taVNS led to a rapid pupil dilation reaching its half-maximum (2.29% over baseline) at 0.57 s after stimulation onset, peaking (4.57% ...

9. nature.com nature.com/articles/s41598-025-17821-5

The effects of non-invasive transcutaneous auricular vagus ... Delivered through a portable device, taVNS is more accessible and poses as a less risky approach to patients in comparison to the surgically ...