VNS for Epilepsy

(VNS-IG Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Louisville

Must not be taking: Anticholinergics, Corticosteroids, Antiarrhythmics, others

Disqualifiers: Pregnancy, Infection, Cancer, Autoimmune, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Vagal nerve stimulation is a neurosurgical procedure consisting of implantation of an impulse generator battery with leads placed into the vagus nerve in the neck. This procedure was FDA approved for epilepsy in the 1990s and is commonly performed as an outpatient surgery. The mechanism of action is not well understood; however it is increasingly recognized that electrical stimulation of the vagus nerve may impact other organ systems in the body including the immune and gastrointestinal systems. Concrete characterization of the peripheral effects of VNS in human gut microbiome and immune systems will: (1) elucidate peripheral mechanism of action of chronic VNS therapy, (2) identify peripheral preoperative biomarker of VNS efficacy, and (3) create a foundation for research investigating new GM and IM-related disease indications for VNS. The primary objective of this study is to characterize the pre- and post-operative oral and gut microbiome of patients implanted with vagal nerve stimulator (VNS) for epilepsy. Secondary objectives of this study include: (1) to characterize the pre-operative and post-operative immune profile of patients undergoing VNS implantation for epilepsy, (2) to elucidate whether oral and/or gut microbiota changes are related to VNS efficacy for epilepsy and (3) identification of a biomarker predicting VNS efficacy.

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

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking high effect anticholinergic or corticosteroid medications within 30 days before joining. Moderate to low effect medications will be reviewed by the study leader.

What data supports the effectiveness of the treatment Vagal nerve stimulation (VNS) for epilepsy?

Research shows that Vagal nerve stimulation (VNS) can help control seizures in people with epilepsy who do not respond to medication. Studies have found that VNS is used worldwide and can be effective for patients who are not suitable for surgery, although it may not work for everyone. ^{1 2 3 4 5}

Is Vagus Nerve Stimulation (VNS) safe for humans?

Vagus Nerve Stimulation (VNS) is generally considered safe for treating epilepsy, with its safety documented in studies from Europe and North America. However, there can be rare significant complications, and its safety profile has been evaluated in various populations. ^{6 7 8 9 10}

How is the treatment VNS for epilepsy different from other treatments?

Vagal nerve stimulation (VNS) is unique because it involves a small device implanted in the body that sends electrical signals to the vagus nerve, unlike traditional epilepsy treatments that often rely on medication. This method is used for patients whose seizures do not respond to drugs, offering a non-drug alternative to manage epilepsy. ^{2 4 11 12 13}

Research Team

Eligibility Criteria

This trial is for individuals with epilepsy who are getting a vagal nerve stimulator (VNS) implanted and can visit a Louisville-based neurologist. It's not for those who've had VNS before, have heart rhythm problems or devices, cancer history, recent immunomodulators or steroids use, current pregnancy, chemotherapy history, or recent cholinergic/anticholinergic drugs.

Inclusion Criteria

I am getting a VNS device for my epilepsy for the first time.

Documented follow up with a Louisville-based neurologist in the past 1 year or documented ability to follow to travel to Louisville for outpatient medical care

Exclusion Criteria

I have previously been treated with VNS.

I have a heart rhythm problem or a device like a pacemaker.

I have taken steroids in the last month or might during the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Assessment

Characterization of pre-operative oral and gut microbiome and immune profile

4 weeks

1 visit (in-person)

Surgical Procedure

Implantation of vagal nerve stimulator (VNS) for epilepsy

1 day

1 visit (in-person)

Post-operative Monitoring

Characterization of post-operative oral and gut microbiome and immune profile

1 year

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vagal nerve stimulation (VNS) (Neurostimulation Device)

Trial Overview The study tests how VNS affects the gut microbiome and bowel habits in epilepsy patients. It also looks at changes in the autonomic and immune systems after surgery. The goal is to understand if these changes relate to how well VNS controls seizures.

Participant Groups

Group I: Patients undergoing device implantation Experimental Treatment 1 Intervention

Patients undergoing device implantation with vagal nerve stimulator (VNS) for epilepsy

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

LivaNova

Industry Sponsor

Trials

66

Recruited

31,100+

Vladimir A. Makatsaria

LivaNova

Chief Executive Officer since 2024

Bachelor of Arts in Physiology, Master of Healthcare Administration, and Master of Business Administration from the University of Minnesota

Dr. Deanna Wilke

LivaNova

Chief Medical Officer since 2023

MD from Harvard Medical School

Norton Foundation

Collaborator

Trials

1

Recruited

30+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Findings from Research

Vagal nerve stimulation (VNS) is a safe and effective palliative treatment for drug-resistant epilepsy, with 12 out of 32 patients (37.5%) experiencing a significant reduction in seizures of more than 50% after the procedure.

The study followed patients for an average of 6 years, and no surgical complications were reported, highlighting the long-term safety of VNS in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Adverse Events and Outcome in a Series of Patients with Long-Term Follow-Up. Morace, R., Di Gennaro, G., Quarato, PP., et al.[2017]

The study identified a specific electrophysiological response called the larynx compound action potential (LCMAP) that occurs approximately 3 ms after vagus nerve stimulation (VNS), which can serve as an objective indicator of effective nerve activation.

LCMAP was successfully recorded in 11 out of 21 rats immediately after surgery, while others required a recovery period, suggesting that monitoring LCMAP could help determine the optimal timing for increasing VNS therapy in patients with refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated assessment of larynx compound muscle action potentials using a self-sizing cuff electrode around the vagus nerve in experimental rats. El Tahry, R., Mollet, L., Raedt, R., et al.[2011]

In a study of 138 patients with refractory epilepsy, vagus nerve stimulation (VNS) led to a significant average reduction of 51% in monthly seizure frequency over a mean follow-up of 44 months, demonstrating its efficacy as an adjunctive treatment.

The responder rate, defined as patients experiencing at least a 50% reduction in seizures, was 59%, with 9% of patients achieving complete seizure freedom, indicating that VNS can provide substantial benefits for many patients with difficult-to-treat epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. De Herdt, V., Boon, P., Ceulemans, B., et al.[2007]

In a study involving six WAG/Rij rats, vagal nerve stimulation (VNS) significantly reduced the total duration of spike and wave complexes (SWC) by 61.8% and the number of activities by 78%, indicating its efficacy in managing non-convulsive epilepsy.

The positive effects of VNS were observed to persist even 15 days after the stimulation ended, suggesting a potential long-term benefit of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Acute and Delayed Effects of Vagal Nerve Stimulation on an Absence Epilepsy Model in WAG/Rij. Uyar, R., Turk, CC., Isik, N., et al.[2018]

Vagal nerve stimulation (VNS) is considered a safe alternative therapy for epilepsy, although it can have rare but significant complications.

The study highlights cases of four patients who were implanted with VNS without prior video-EEG monitoring, suggesting a need for better guidelines on the necessity of this monitoring before VNS implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video EEG monitoring prior to vagal nerve stimulator implantation. Attarian, H., Dowling, J., Carter, J., et al.[2019]

In a study of 35 patients with refractory epilepsy, vagal nerve stimulation (VNS) led to a significant median reduction in seizure frequency of 55.65%, with some patients experiencing over 90% improvement and two becoming seizure-free.

VNS was found to be safe and well-tolerated, with only transient adverse effects that could be managed by adjusting stimulation parameters, and it also improved quality of life, memory, mood, and alertness in most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic intermittent vagal nerve stimulation in the treatment of refractory epilepsy: experience in Mexico with 35 cases. Alonso-Vanegas, MA., Austria-Velásquez, J., López-Gómez, M., 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]

Vagus nerve stimulation (VNS) has been shown to be a safe and effective treatment for intractable epilepsy, supported by randomized clinical studies in Europe and North America.

In this report, the authors present their experience with VNS in 6 Chinese patients, highlighting both the indications for the device and the associated challenges encountered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for seizure control: Local experience. Hsiang, JN., Wong, LK., Kay, R., et al.[2019]

Vagus nerve stimulation (VNS) is an effective and well-tolerated treatment for drug-resistant focal epilepsy, with high-frequency stimulation showing a 73% greater likelihood of achieving a 50% or more reduction in seizure frequency compared to low-frequency stimulation, based on data from 439 participants across five randomized controlled trials.

While VNS is generally well tolerated, common adverse effects include hoarseness and dyspnoea, particularly with high-level stimulation, indicating the need for careful monitoring and further research to confirm these findings and assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for focal seizures. Panebianco, M., Rigby, A., Marson, AG.[2023]

In a preliminary study of eight pediatric patients with medically intractable seizures, vagus nerve stimulation (VNS) showed promising results, with five patients experiencing over 50% reduction in seizure frequency and four achieving a reduction of 90% or more.

VNS was well tolerated with no significant adverse effects reported during the follow-up period of 9 to 33 months, indicating it is a safe and effective alternative treatment for managing intractable seizures in children and adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term results of vagus nerve stimulation in pediatric patients with refractory epilepsy. Chen, CY., Lee, HT., Chen, CC., et al.[2016]

In a study of 14 epilepsy patients with vagal nerve stimulators, those who experienced a 50% or greater reduction in seizures (responders) had lower preoperative connections between the left hippocampus and both the left and right thalamus compared to non-responders, suggesting these connections may help predict treatment outcomes.

The study found that varying the stimulation current (up to 1.5 mA) and duration (up to 3 months) did not significantly alter hippocampal-thalamic connectivity, indicating that these parameters may not be critical for immediate changes in brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vagal nerve stimulation on hippocampal-thalamic functional connectivity in epilepsy patients. Zhu, J., Xu, C., Zhang, X., et al.[2021]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Adverse Events and Outcome in a Series of Patients with Long-Term Follow-Up. [2017]

2. Poland pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation in drug-resistant epilepsy. Experience with 23 patients]. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Repeated assessment of larynx compound muscle action potentials using a self-sizing cuff electrode around the vagus nerve in experimental rats. [2011]

4. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. [2007]

5. Turkey pubmed.ncbi.nlm.nih.gov

The Acute and Delayed Effects of Vagal Nerve Stimulation on an Absence Epilepsy Model in WAG/Rij. [2018]

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

Video EEG monitoring prior to vagal nerve stimulator implantation. [2019]

7. Mexico pubmed.ncbi.nlm.nih.gov

Chronic intermittent vagal nerve stimulation in the treatment of refractory epilepsy: experience in Mexico with 35 cases. [2022]

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. [2021]

9. 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]

10. Scotland pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for seizure control: Local experience. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for focal seizures. [2023]

12. Singapore pubmed.ncbi.nlm.nih.gov

Short-term results of vagus nerve stimulation in pediatric patients with refractory epilepsy. [2016]

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

The effect of vagal nerve stimulation on hippocampal-thalamic functional connectivity in epilepsy patients. [2021]