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

22 Participants Needed

Trial Summary

What is the purpose of this trial?

To generate preliminary safety and effectiveness data for brain-responsive neurostimulation of thalamocortical networks as an adjunctive therapy in reducing the frequency of generalized seizures in individuals 12 years of age or older with Lennox Gastaut Syndrome (LGS) who are refractory to antiseizure medications. The intent is to determine the feasibility and the optimal design of a subsequent pivotal study in order to expand the indication for use for the RNS System as a treatment for patients with medically intractable LGS.

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 data supports the effectiveness of the RNS System treatment for Lennox-Gastaut Syndrome?

Research shows that the RNS System, originally used for epilepsy, has helped reduce seizures by 75-99% in children with Lennox-Gastaut Syndrome and autism over more than a year of follow-up. This suggests it can be a safe and effective treatment for reducing seizures in this condition. ^{1 2 3 4 5}

Is the RNS System generally safe for humans?

The RNS System has been approved by the US Food and Drug Administration for treating focal epilepsy, based on safety and effectiveness data from clinical trials. It is considered a safe alternative for patients who do not respond to traditional medications, as it does not involve removing brain tissue. ^{2 3 6 7 8}

How does the RNS System treatment for Lennox-Gastaut Syndrome differ from other treatments?

The RNS System is unique because it is an implantable device that detects abnormal brain activity and delivers electrical stimulation to prevent seizures, unlike traditional medications that are taken orally. This system provides real-time, on-demand treatment and offers continuous monitoring of brain activity, which is not available with standard drug therapies. ^{2 5 6 7 9}

Research Team

Martha Morrell, MD

Principal Investigator

NeuroPace, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

References

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

Evidence of state-dependence in the effectiveness of responsive neurostimulation for seizure modulation. [2022]

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

A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. [2021]

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

Centromedian thalamic responsive neurostimulation for Lennox-Gastaut epilepsy and autism. [2021]

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

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

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

Operative Technique and Lessons Learned From Surgical Implantation of the NeuroPace Responsive Neurostimulation® System in 57 Consecutive Patients. [2021]

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

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures. [2021]

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

Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. [2021]

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

Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique. [2020]