Vagal Nerve Stimulation for Dilated Pupil

Overseen By Justin Cottrell

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Disqualifiers: Heart abnormalities, Dysautonomias, Lung diseases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how stimulating Arnold's Nerve, part of the vagus nerve, affects pupil size during cochlear implant surgery. Researchers aim to determine if this nerve stimulation can dilate pupils in a medically beneficial way. The trial includes two groups: one receives nerve stimulation during cochlear implant surgery, while the other does not. Individuals already scheduled for cochlear implant surgery, without a history of ear surgeries or specific health conditions like heart problems or asthma, may qualify for this study. As an unphased trial, it offers a unique opportunity to contribute to medical knowledge and potentially improve surgical outcomes.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the research team or your doctor.

What prior data suggests that Arnold's Nerve Stimulation is safe for pupillary dilation?

Research has shown that vagal nerve stimulation (VNS) is generally safe. However, some people have experienced side effects such as changes in voice, coughing, headaches, and pain.

The main purpose of this treatment is to measure changes in the pupils during cochlear implant surgery. Awareness of these possible side effects is important for setting expectations. Overall, most people tolerate the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for dilated pupil, which typically involve medications or surgical interventions to manage symptoms or underlying conditions, Arnold's Nerve Stimulation offers a unique approach by using electrical stimulation of the vagal nerve during cochlear implantation surgery. This method specifically targets the Arnold's nerve to potentially influence pupil dilation directly. Researchers are excited because this technique could offer a non-invasive alternative that harnesses the body's own neural pathways to achieve therapeutic effects, possibly leading to quicker and more targeted results compared to conventional methods.

What evidence suggests that Arnold's Nerve Stimulation is effective for dilated pupil?

Research shows that stimulating the vagus nerve can enlarge pupils. Some studies found that this stimulation, especially when applied to Arnold's nerve, effectively causes pupil dilation. In this trial, participants in the "Vagal Nerve Stimulation during Cochlear Implantation Surgery" arm will receive electrical stimulation during the procedure to stimulate Arnold's nerve and measure pupil dilation. Other research supports that short-term vagus nerve stimulation can temporarily enlarge pupils, linking it to certain brain activities. Overall, these findings suggest that vagus nerve stimulation might help treat conditions related to enlarged pupils. ^{1 2 6 7 8}

Who Is on the Research Team?

J. Thomas Roland Jr.

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 years old who are undergoing cochlear implantation or vagal nerve stimulator implantation and are willing to participate. It's not for those with a history of ear surgery, congenital malformations, pregnant/breastfeeding individuals, or anyone with certain medical conditions like heart arrhythmias, lung diseases, ulcers, dysautonomias, vasovagal syncope, or pre-existing hoarseness.

Inclusion Criteria

I am over 18 and getting a vagal nerve stimulator implant.

I am scheduled for cochlear implant surgery.

I am scheduled for a vagal nerve stimulator implantation.

Exclusion Criteria

You will be excluded if you have a history of fainting due to a medical condition.

Patients undergoing vagal nerve stimulator implantation: pregnant or breastfeeding

I do not have lung diseases like asthma causing shortness of breath.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive electrical stimulation of Arnold's Nerve during cochlear implantation surgery to measure pupil dilation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Arnold's Nerve Stimulation

Trial Overview The study tests how the pupil dilates when Arnold's Nerve (part of the vagus nerve) is stimulated with an electrical device during routine cochlear implant surgery. The aim is to understand the connection between this stimulation and changes in pupil size.

How Is the Trial Designed?

Group I: Vagal Nerve Stimulation during Cochlear Implantation Surgery Experimental Treatment 1 Intervention

Participants undergoing cochlear implantation will receive electrical stimulation during the procedure to stimulate the Arnold's nerve to measure pupil dilation.

Group II: Vagal Nerve Stimulator Implantation Active Control 1 Intervention

Control cohort undergoing vagal nerve stimulator implantation.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

In a study involving 33 healthy young volunteers, transcutaneous auricular vagus nerve stimulation (taVNS) did not significantly affect pupil size or pupil responses, which were hypothesized to be potential biomarkers for the effectiveness of taVNS.

Despite the expectation that taVNS would enhance pupil responses due to its mechanism of action linked to locus coeruleus activation, the results suggest that pupil measures may not be reliable predictors of individual responses to taVNS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No modulation of pupil size and event-related pupil response by transcutaneous auricular vagus nerve stimulation (taVNS). Keute, M., Demirezen, M., Graf, A., et al.[2021]

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]

The study involving 49 participants demonstrated that transcutaneous auricular vagus nerve stimulation (taVNS) can enhance pupil dilation, which is a biomarker for noradrenergic activity, indicating a potential mechanism of action for taVNS.

Higher stimulation settings of taVNS resulted in a linear increase in pupil dilation, supporting the idea that taVNS may activate noradrenergic pathways, although it also caused more intense and unpleasant sensations compared to sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short bursts of transcutaneous auricular vagus nerve stimulation enhance evoked pupil dilation as a function of stimulation parameters. D'Agostini, M., Burger, AM., Franssen, M., et al.[2023]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Citations

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

Does transcutaneous auricular vagus nerve stimulation ... Across 18 studies, the meta-analysis shows moderate evidence against an effect of taVNS on pupil dilation. A: Contour-enhanced funnel plot showing standard ...

2. withpower.com withpower.com/trial/phase-hearing-loss-4-2023-67b0a

Vagal Nerve Stimulation for Dilated Pupil Some studies show that this type of stimulation can increase pupil size, indicating its potential effectiveness for treating dilated pupils.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X22002388

Characterization of vagus nerve stimulation-induced ... In humans, it has been shown that during VNS the average pupil diameter is larger compared to when VNS is turned off [14]. However, no stimulation-locked ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37348704/

A replication of Sharon et al. (2021, Journal of Neuroscience) Conclusion: Our findings support the effectiveness of short-term taVNS in inducing transient pupil dilation, a correlate of phasic noradrenergic activity.

5. jneurosci.org jneurosci.org/content/41/2/320

Transcutaneous Vagus Nerve Stimulation in Humans ... Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4–5 s after trial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7810665/

Transcutaneous Vagus Nerve Stimulation in Humans Induces ... Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4–5 s after trial onset) that was ...

7. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(23)01802-8/fulltext

A replication of Sharon et al. (2021, Journal of Neuroscience) Our findings support the effectiveness of short-term taVNS in inducing transient pupil dilation, a correlate of phasic noradrenergic activity.

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

Evaluating phasic transcutaneous vagus nerve stimulation ... A promising study in humans stimulated with brief bursts (3.4 s) demonstrated increased pupil dilation, which is consistent with the results ...