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

Trial Summary

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 data supports the effectiveness of this treatment for epilepsy?

Vagus nerve stimulation (VNS) is a well-established treatment for epilepsy, particularly for patients whose seizures do not respond to medication. Research has shown that VNS can significantly reduce seizure frequency, and it is also approved for treatment-resistant depression, indicating its potential effectiveness in other conditions. ^{1 2 3 4 5}

Is vagus nerve stimulation (VNS) generally safe for humans?

Vagus nerve stimulation (VNS) is generally considered safe, but some people may experience complications like changes in heart rate during surgery or other side effects after the device is implanted. ^{1 6 7 8 9}

How is VNS treatment for epilepsy different from other treatments?

Vagus nerve stimulation (VNS) is unique because it involves a device implanted to stimulate the vagus nerve, which can help reduce seizures in people with epilepsy who do not respond to medication. Unlike traditional drug treatments, VNS is a surgical procedure and works by sending electrical impulses to the brain through the vagus nerve. ^{1 2 3 5 10}

What is the purpose of this trial?

This Anchillary project uses a refined technique of ultrasound-guided microneurography of the human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used safely to-date in 44 prior study participants. The overall goal of this project is to build upon prior data obtained using this approach by undertaking a detailed neurophysiological investigation of the human vagus nerve and to identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with implanted VNS devices in response to different stimulation parameters. In addition to providing data in unprecedented detail into the physiology of the human vagus nerve, this project will investigate different stimulus intensities, durations and frequencies that differentially excite myelinated and unmyelinated nerve fibers. These results will inform the CSP and guide future development of novel neural interfaces for VNS for various clinical applications.

Research Team

John Osborn

Principal Investigator

University of Minnesota

Vaughan G Macefield, PhD

Principal Investigator

Monash University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intra-operative monitoring as an adjuvant to standard vagus nerve stimulation implantation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation. [2022]

3. United States 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. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Intraoperative nerve stimulation during vagal nerve stimulator placement. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. [2022]

7. United States 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. [2021]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Complications of chronic vagus nerve stimulation for epilepsy in children. [2004]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Modifications of sleep EEG induced by chronic vagus nerve stimulation in patients affected by refractory epilepsy. [2008]