RNS System for Lennox-Gastaut Syndrome

Recruiting at 5 trial locations

Overseen By Tricia Cunningham

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: NeuroPace

Must be taking: Antiseizure medications

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Unstable psychiatric disorder, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called the RNS System (Responsive Neurostimulation System) to assist individuals with Lennox-Gastaut Syndrome (LGS) who continue to experience frequent seizures despite multiple medications. The goal is to determine if this brain-responsive neurostimulation system can safely reduce seizure frequency. The trial tests two different treatment setups. It suits individuals aged 12 and up who experience at least five significant seizures a month and have not found success with other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You will not have to stop taking your current antiseizure medications, but you must have a stable medication regimen for at least 2 months before joining the trial and be willing to keep it stable during the study period.

What prior data suggests that the RNS System is safe for treating Lennox-Gastaut Syndrome?

Research shows that the RNS System may help treat certain types of seizures. Previous studies found it safe and effective for people with hard-to-treat focal seizures. The system sends small electrical signals to the brain to help control seizures.

While specific safety data for the RNS System in treating Lennox-Gastaut Syndrome (LGS) is still being collected, some information is available. The system has been used for other conditions, and reports of problems are rare, suggesting it is generally well-tolerated. It has also reduced seizures over the long term in other cases, which is promising.

For those considering joining a trial, it's important to know that while the RNS System is being tested for LGS, it has a history of safety in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RNS System for Lennox-Gastaut Syndrome because it offers a unique approach to managing seizures. Unlike standard treatments, which often involve medications to control seizures, the RNS System is a responsive neurostimulation device that monitors brain activity and delivers electrical pulses to prevent seizures before they start. This system can be personalized to each patient's brain activity patterns, potentially offering more targeted and effective control of seizures. Moreover, the trial is exploring two specific stimulation patterns—high-frequency short bursts and low-frequency long bursts—providing insights into optimizing the device's effectiveness for different patients.

What evidence suggests that the RNS System could be effective for Lennox-Gastaut Syndrome?

Research has shown that the RNS System, a device responding to brain activity, may help reduce seizures in people with Lennox-Gastaut Syndrome (LGS). Long-term studies suggest that this device can continue to reduce seizures over time. Patients have reported feeling better with each year of using the device. In this trial, participants will join different treatment arms to test the RNS System's effectiveness with varying stimulation patterns. Although researchers are still testing the RNS System specifically for LGS, its success in similar conditions offers hope for those with hard-to-treat seizures. ^{1 2 3 4 5}

Who Is on the Research Team?

Martha Morrell, MD

Principal Investigator

NeuroPace, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older with Lennox Gastaut Syndrome (LGS) who have frequent generalized seizures and haven't responded well to at least two antiseizure medications. They should not be on certain epilepsy diets, have a stable medication regimen, and can't be using other electrical brain stimulation devices. Women of childbearing age must use reliable contraception.

Inclusion Criteria

Your brain wave test shows patterns linked to a condition called Lennox-Gastaut syndrome.

My epilepsy doesn't respond well to at least 2 medications without severe side effects.

My seizures do not originate from a specific area of my brain.

Exclusion Criteria

I have not had any severe mental health issues or suicidal thoughts in the last 6 months.

Participant is pregnant

Participant is participating in a therapeutic investigational drug or device study (including other RNS System studies)

Timeline for a Trial Participant

Baseline Period

Participants undergo baseline assessments prior to implant surgery

2-4 weeks

Implant (surgery)

Surgical implantation of neurostimulators and leads

1 week

Post-Op Period

Participants recover from surgery and initial post-operative assessments are conducted

4 weeks

Blinded Evaluation Period

Participants undergo three treatment blocks with two active and one sham stimulation

12 months

Open Label Period

Participants receive active treatment and are monitored every 3 months

12 months

Long Term Follow-Up Period

Participants are monitored for long-term safety and effectiveness every 3 months

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• RNS System

Trial Overview The study tests the RNS System's safety and effectiveness as an additional treatment for reducing seizure frequency in LGS patients. It aims to gather initial data to help design a larger pivotal study that could extend the device's approved uses.

How Is the Trial Designed?

Group I: Condition A Active Control 1 Intervention

high-frequency short bursts (HFSB: 100 Hz, 160 µs pulse width, 200 msec burst)

Group II: Condition B Active Control 1 Intervention

low-frequency long bursts (LFLB: 5 Hz, 160 µs pulse width, 5 sec burst)

Who Is Running the Clinical Trial?

NeuroPace

Lead Sponsor

Trials

11

Recruited

1,500+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study involving 57 patients with medically refractory focal epilepsy, the Responsive Neurostimulation (RNS) System demonstrated a median reduction in seizure frequency of 60%, with 27% of patients achieving complete seizure freedom after a median follow-up of 23.1 months.

The surgical techniques described for implanting the RNS System were safe, with no infections or major complications reported, although some patients experienced lead fractures requiring exchanges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operative Technique and Lessons Learned From Surgical Implantation of the NeuroPace Responsive Neurostimulation® System in 57 Consecutive Patients. Krucoff, MO., Wozny, TA., Lee, AT., et al.[2021]

In patients with the RNS System for epilepsy, a significant reduction in 'long episodes' of electrographic seizures within the first week of starting new antiseizure drugs (ASDs) was highly predictive of the medication's efficacy.

In a larger multicenter study, a decrease in 'episode starts' by 50% or more within the first 1-2 weeks was 90% specific for effective medications, suggesting that early neurophysiological data can guide quicker medication adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. Quraishi, IH., Mercier, MR., Skarpaas, TL., et al.[2021]

In a study of 150 patients treated with the RNS System for at least one year, the median reduction in seizure frequency was 67% at one year, increasing to 82% at three years, demonstrating the long-term effectiveness of this neurostimulation therapy.

The safety profile was favorable, with a low infection rate of 2.9% and no long-lasting neurological consequences from complications, indicating that the RNS System is a safe option for patients with medically intractable focal onset seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures. Razavi, B., Rao, VR., Lin, C., et al.[2021]

The NeuroPace® RNS® System is a safe and effective neuromodulation device for patients with epilepsy who do not respond to traditional antiseizure medications, providing a nondestructive alternative to surgical resection.

Clinical trials have shown that the RNS System can detect and respond to epileptiform activity by delivering targeted electrical stimulation, which may lead to improved seizure control and could be adapted for other neurological disorders using advanced machine learning techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. Jarosiewicz, B., Morrell, M.[2021]

The responsive neurostimulator (RNS) has been clinically used since 2013 to treat patients with medically refractory partial epilepsy, showing significant seizure reduction compared to sham stimulation in a randomized clinical trial.

Long-term use of the RNS has provided valuable data on epilepsy dynamics, including insights into seizure onset patterns and the potential for early detection of treatment benefits, although optimal patient selection and lead placement remain areas for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive neurostimulation: Review of clinical trials and insights into focal epilepsy. Geller, EB.[2019]

In a study involving 16 patients with medically refractory focal epilepsy, robotic-assisted implantation of the responsive neurostimulation system (RNS) led to an impressive average seizure reduction of 82% at 6 months and 90% at 1 year, demonstrating its efficacy as a treatment.

The use of the ROSA robot for targeting ictal-onset zones resulted in a highly accurate lead placement, with only a 0.165-mm discrepancy between the expected and actual lead locations, indicating a precise method for improving seizure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. Tran, DK., Paff, M., Mnatsakanyan, L., et al.[2021]

The study involved 12 patients who underwent robotic-assisted placement of depth electrodes for the RNS® system, showing a mean seizure reduction of approximately 40% over two years, which aligns with results from previous pivotal trials.

Robotic-assisted stereotactic techniques provided a safe and accurate method for electrode placement, with a mean operative time of 121 minutes and minimal deviation from the intended target, although two patients experienced wound infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique. McGovern, RA., Alomar, S., Bingaman, WE., et al.[2020]

Citations

1. investors.neuropace.com investors.neuropace.com/news-releases/news-release-details/neuropace-completes-enrollment-feasibility-study-rns-system

NeuroPace Completes Enrollment in Feasibility Study of RNS ... The study will evaluate the safety and effectiveness of the RNS System in treating seizures associated with LGS. “We are pleased to announce the advancement of ...

2. aesnet.org aesnet.org/abstractslisting/evaluating-patient-assessments-in-lennox-gastaut-syndrome-baseline-insights-from-the-rns-lgs-system-feasibility-trial

evaluating patient assessments in lennox-gastaut syndrome This feasibility trial aims to generate preliminary safety and effectiveness data for brain-responsive neurostimulation as an adjunctive ...

3. neuropace.com neuropace.com/providers/clinical-trials/

RNS System Clinical Trials The purpose of the RNS System Lennox-Gastaut Syndrome (LGS) study is to generate preliminary safety and effectiveness data for brain-responsive neurostimulation ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/17434440.2025.2557406

Future potential of responsive neurostimulation for the ... Table 1. Efficacy and Outcomes of Responsive Neurostimulation (RNS) in Lennox-Gastaut Syndrome (LGS). Download CSVDisplay Table.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7545608/

Centromedian thalamic responsive neurostimulation for ... Long‐term data have shown that RNS provides sustained seizure reduction with continued improvement with each year of treatment including ...