VNS for Epilepsy

(VNS-IG Trial)

Recruiting at 3 trial locations

Overseen By Meena A Vessell, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Louisville

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

Disqualifiers: Pregnancy, Infection, Cancer, Autoimmune, 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: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how vagal nerve stimulation (VNS) affects the body, particularly the gut and immune system, in people with epilepsy. VNS involves a small device placed in the neck to help control seizures. Researchers aim to determine how this treatment alters bacteria in the mouth and gut and whether these changes can predict VNS effectiveness for epilepsy. The trial seeks participants receiving VNS for the first time who can travel to Louisville or specific universities for follow-up care.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance understanding of epilepsy treatment.

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 prior data suggests that this device is safe for epilepsy patients?

Research has shown that vagal nerve stimulation (VNS) has been safely used to treat epilepsy since the 1990s. This treatment involves placing a small device in the neck to help control seizures. Studies have found that VNS can reduce the number of seizures by more than half in 40-70% of patients, with most experiencing less anxiety and an improved quality of life.

VNS is generally well-tolerated regarding safety. The procedure is usually performed as outpatient surgery, allowing patients to return home the same day. Most side effects are mild and may include changes in voice or throat pain, which often improve over time. The long history of VNS use for epilepsy strongly supports its safety for many individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Vagal nerve stimulation (VNS) is unique because it offers a non-drug approach to managing epilepsy, unlike typical medications like anti-seizure drugs. VNS works by sending electrical impulses to the vagus nerve, which then influences brain activity to reduce seizure frequency. Researchers are excited about VNS because it provides an alternative for patients who don't respond well to medication, potentially offering improved quality of life with fewer side effects associated with long-term drug use.

What is the effectiveness track record for Vagal nerve stimulation (VNS) in treating epilepsy?

Research has shown that vagal nerve stimulation (VNS) can reduce seizures in many people with epilepsy. About 45-65% of patients experience a 50-100% reduction in seizures after six months of treatment. Improvements in seizure frequency, duration, and intensity have been observed in 65% of patients who do not respond to medication. Some studies found that after just 8 weeks, 12% of participants became completely seizure-free, and 24% had fewer seizures. VNS is already approved for treating epilepsy, and these findings support its effectiveness in managing the condition. Participants in this trial will undergo device implantation with a vagal nerve stimulator to further evaluate its impact on epilepsy. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Vagal nerve stimulation (VNS)

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.

How Is the Trial Designed?

Group I: Patients undergoing device implantation Experimental Treatment 1 Intervention

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

Vagal nerve stimulation (VNS) is already approved in United States, European Union for the following indications:

Approved in United States as VNS Therapy for:

• Epilepsy
• Treatment-resistant depression
• Stroke recovery

Approved in European Union as VNS Therapy for:

• Epilepsy
• Treatment-resistant depression

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Vagal nerve stimulation (VNS) has shown to be an effective treatment for drug-resistant epilepsy, with over 80% of patients experiencing a significant reduction in seizures (more than 50% reduction or complete cessation) after 24 months of therapy.

While there are some side effects related to local irritation of the vagal nerve, these are rare and generally do not lead to serious complications, making VNS a safe alternative to neurosurgery for epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation in drug-resistant epilepsy. Experience with 23 patients]. Zwoliński, P., Roszkowski, M., Drabik, K., et al.[2015]

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]

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]

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]

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 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]

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]

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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11543756/

Vagus nerve stimulation (VNS): recent advances and future ... After 8 weeks of treatment, 12% of participants were seizure-free and 24% had a reduction in seizure frequency. After 24 weeks, the number of ...

3. 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.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X2200095X

VNS parameters for clinical response in Epilepsy VNS response in epilepsy may be maximized near 1.625 mA, 30 seconds ON, 3 minutes OFF. Shorter epilepsy duration and longer time on therapy are associated with ...

5. neurology.org neurology.org/doi/10.1212/WNL.0b013e3182a393d1

Vagus nerve stimulation for the treatment of epilepsy Based on data from 14 Class III studies, VNS is possibly effective in achieving >50% seizure frequency reduction (responder rate). In the pooled analysis of 481 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12494630/

Outcome and predictors of response to vagus nerve ... Over the past two decades, numerous studies have demonstrated that VNS can reduce seizure frequency by more than 50% in nearly 40–70% of ...

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

Learnings from 30 years of reported efficacy and safety ... Although the median reduction in seizure frequency after three months of VNS therapy was similar between the two groups (50.0 % in early-VNS group versus 48.2 % ...

8. epilepsy.com epilepsy.com/treatment/devices/vagus-nerve-stimulation-therapy

Vagus Nerve Stimulation for Seizures - Epilepsy Foundation Recovery time after a seizure may be shorter for some people. · 8 of 10 people reported an improved quality of life. · About 6 of 10 reported less worry about ...