VNS Monitoring for Epilepsy

Recruiting at 1 trial location

Overseen By Kathryn Vera, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Disqualifiers: Pregnant, Smoking, Carotid plaque, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 hours

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the function of the human vagus nerve, focusing on individuals with epilepsy who have an implanted vagus nerve stimulator (VNS). Researchers aim to identify which nerve fibers activate during VNS and how different settings affect these fibers. The trial will record nerve activity using intraneural microelectrode recordings to enhance future treatments for epilepsy and other conditions. It seeks participants with epilepsy who have VNS devices, as well as healthy individuals without them, who can stand unassisted for 5 minutes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

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.

What prior data suggests that this technique is safe for use in humans?

Research has shown that Vagus Nerve Stimulation (VNS) has been safely used in many studies. In previous research, patients with medication-resistant epilepsy experienced significant benefits from VNS. About 45-65% of these patients reduced their seizures by 50-100% after six months of treatment.

Side effects are usually mild and may include changes in voice or a sore throat, while serious issues remain rare. The method used in this trial, ultrasound-guided microneurography, has been safely performed on 44 people without serious problems.

Overall, the safety data for VNS is promising. For those considering joining a VNS trial, the treatment has a strong safety record in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to monitor epilepsy using a combination of VNS (Vagus Nerve Stimulation) and intraneural recordings. Unlike traditional epilepsy treatments, which often rely on medication to manage symptoms, this approach aims to precisely track and respond to brain activity associated with seizures. The unique aspect here is the direct recording of neural activity from within the nerve itself, providing real-time insights into how the brain and nervous system are functioning. This could potentially lead to more personalized and effective interventions for people with drug-resistant epilepsy, offering hope for those who haven’t found success with existing treatments.

What evidence suggests that this trial's techniques could be effective for epilepsy?

Research shows that Vagus Nerve Stimulation (VNS), which participants in this trial may receive, can help control seizures in people whose epilepsy doesn't respond to medication. Studies have found that VNS can reduce seizures by 50% or more in many patients. For instance, one study found that 82.9% of patients experienced at least a 50% reduction in seizures after 12 years of VNS treatment. Another study reported that 80% of patients responded positively to VNS, with a 66% reduction in absence seizures. Overall, this evidence suggests that VNS is a promising option for managing seizures when other treatments haven't worked. ^{3 4 5 6 7}

Who Is on the Research Team?

Vaughan G Macefield, PhD

Principal Investigator

Monash University

John Osborn

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-40 with epilepsy who have health insurance and an implanted VNS device. It's not for pregnant individuals, those whose vagus nerve isn't visible on ultrasound, or if the VNS electrodes aren't suitably placed. Smokers must abstain on experiment day, and participants can't have significant carotid artery plaque.

Inclusion Criteria

I have Medicare or similar health insurance.

English speaking

Exclusion Criteria

I cannot stand by myself for 5 minutes.

Pregnant

The researchers have other health reasons for not including you in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo ultrasound-guided microneurography and vagal nerve stimulation to assess nerve activity

4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the neurophysiological investigation

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Record multi-unit activity from intraneural sites
• VNS stimulation and intraneural recordings

Trial Overview The study tests how different stimulation settings of a Vagus Nerve Stimulation (VNS) device affect nerve fibers in the human vagus nerve. Using ultrasound-guided microneurography, researchers record nerve activity to guide future development of neural interfaces for clinical applications.

How Is the Trial Designed?

Group I: non-VNS participants Experimental Treatment 1 Intervention

participants without implanted VNS devices

Group II: VNS Experimental Treatment 1 Intervention

participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

In a review of 111 patients who received vagus nerve stimulation (VNS) for refractory epilepsy, three cases of intraoperative bradycardia were observed during device testing, but no adverse cardiac events occurred postoperatively.

Despite the initial bradycardia during testing, all three patients experienced reduced seizure frequency after starting VNS therapy, indicating that VNS is safe and effective for managing epilepsy even when bradycardia is noted during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Ardesch, JJ., Buschman, HP., van der Burgh, PH., et al.[2022]

In a study of 74 children with medically refractory epilepsy who underwent vagus nerve stimulation (VNS), 9.4% experienced complications leading to device removal, with deep infections occurring in 3.5% of cases.

Despite some surgical complications and stimulation-induced symptoms like hoarseness and dysphagia, VNS is considered a viable treatment option for improving seizure control in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of chronic vagus nerve stimulation for epilepsy in children. Smyth, MD., Tubbs, RS., Bebin, EM., et al.[2004]

Vagus nerve stimulation (VNS) is effective in activating laryngeal muscles in patients with drug-resistant epilepsy, with low output currents (0.25-1.00 mA) sufficient for activation, as shown in a study involving 25 patients.

After one year of VNS therapy, while the threshold for activation remained stable, the maximal response amplitude decreased in all patients, indicating a potential change in nerve fiber responsiveness over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation. Bouckaert, C., Raedt, R., Larsen, LE., et al.[2022]

Vagus nerve stimulation (VNS) has been shown to reduce seizures by more than 50% in 55% of children with partial or generalized epilepsy, based on a review of 13 studies involving 470 participants.

VNS is also effective for patients with Lennox-Gastaut syndrome, showing similar seizure reduction rates, and may improve mood in adults with epilepsy, although children are at a higher risk for infection at the implantation site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the guideline development subcommittee of the american academy of neurology. Morris, GL., Gloss, D., Buchhalter, J., et al.[2021]

Chronic vagus nerve stimulation (VNS) significantly increases total EEG power, particularly during NREM sleep, suggesting it enhances brain electrical activity in patients with medically refractory epilepsy.

While the incidence of interictal epileptiform activity (IEA) did not significantly decrease, the duration of these discharges was significantly reduced, indicating potential benefits of VNS in managing epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modifications of sleep EEG induced by chronic vagus nerve stimulation in patients affected by refractory epilepsy. Rizzo, P., Beelke, M., De Carli, F., et al.[2008]

In a study of 66 children aged 3 to 12 undergoing vagus nerve stimulation (VNS) for refractory epilepsy, intra-operative neuro-monitoring (IONM) was used to help ensure correct lead placement and potentially reduce complications.

While IONM was effective in minimizing vocal cord stimulation during the procedure, it did not lead to improved voice-related quality of life outcomes at the 3-month follow-up compared to standard VNS insertion techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-operative monitoring as an adjuvant to standard vagus nerve stimulation implantation. Labuschagne, J., Mutyaba, D., Nel, J., et al.[2022]

Vagus nerve stimulation (VNS) has been shown to reduce seizures by more than 50% in 55% of children with partial or generalized epilepsy and in 55% of patients with Lennox-Gastaut syndrome, based on a review of 13 and 4 studies respectively.

VNS may improve mood in adults with epilepsy and shows a potential increase in seizure reduction rates over time, but children are at a higher risk for infection at the implantation site compared to adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Morris, GL., Gloss, D., Buchhalter, J., et al.[2022]

Chronic vagus nerve stimulation (VNS) significantly reduces seizure frequency in patients with medically refractory partial seizures, showing a median reduction of 20% in the first 3 months and 32% by the end of the first year, based on a study involving 100 patients who completed the treatment.

The initial response to VNS treatment within the first 3 months is a strong predictor of long-term efficacy, suggesting that early improvements can indicate sustained benefits over the course of a year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Vagus Nerve Stimulation Study Group. Salinsky, MC., Uthman, BM., Ristanovic, RK., et al.[2019]

Vagus nerve stimulation (VNS) is an effective therapy for adults and adolescents (12 years and older) with partial onset seizures that do not respond to traditional antiepileptic medications, with over 50,000 patients having received the treatment worldwide.

In addition to epilepsy, VNS is also approved for treatment-resistant depression and shows potential for treating other medical conditions, highlighting its versatility as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. Terry, R.[2020]

In a study of 46 patients undergoing vagal nerve stimulation (VNS) surgery, stimulation of the vagal nerve consistently induced vocal cord responses, confirming the effectiveness of intraoperative monitoring.

The most sensitive area of the vagal nerve was identified in the medial middle region, allowing for lower stimulation thresholds (median 0.2 mA), which could improve the safety and efficacy of VNS procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative nerve stimulation during vagal nerve stimulator placement. Kamada, C., Enatsu, R., Kanno, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12400741/

Long-term efficacy and predictors of vagus nerve ... VNS effectively controls seizures, with effectiveness and seizure-free rates improving over time. Patients with structural factors are at higher ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S105913112400027X

Efficacy of vagus nerve stimulation in managing drug ... VNS reduced absence seizures by 66% in DRAE patients. •. 80% of patients responded positively to VNS therapy. •. Seizure improvement was ...

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1564735/full

Long-term outcome of vagus nerve stimulation therapy in ... observed that 82.9% of patients who received treatment for 12 years experienced a reduction in seizure frequency of at least 50% (7), suggesting ...

4. thejcn.com thejcn.com/DOIx.php?id=10.3988/jcn.2024.0218

Long-Term Efficacy and Quality-of-Life Changes After ... Improvements in seizure frequency, duration, and strength were observed in 65% of the patients with drug-resistant epilepsy treated using VNS.

5. aepi.biomedcentral.com aepi.biomedcentral.com/articles/10.1186/s42494-025-00215-5

Safety and effectiveness of vagus nerve stimulation in patients ... The proportion of patients who experienced a > 50% reduction in seizure frequency was 23% at six months, 36% at 12 months, 65% at 18 months, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33120323/

Learnings from 30 years of reported efficacy and safety ... VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1059131120303095

Learnings from 30 years of reported efficacy and safety ... In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50–100 % seizure frequency reduction is achieved in approximately 45–65 % of ...