Responsive Neurostimulation for Generalized Epilepsy

(NAUTILUS Trial)

Recruiting at 23 trial locations

Overseen By Cairn Seale

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: NeuroPace

Must be taking: Antiseizure medications

Must not be taking: Anticoagulants

Disqualifiers: Pregnancy, Active psychosis, Major depression, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

To demonstrate that the RNS System for thalamic stimulation is safe and effective as an adjunctive therapy for the reduction of primary generalized seizures in individuals 12 years of age or older who have drug-resistant idiopathic generalized epilepsy.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable antiseizure medication regimen during the study, if medically possible. However, rescue benzodiazepine medications for acute seizure clusters are allowed.

What data supports the effectiveness of the Responsive Neurostimulation System treatment for generalized epilepsy?

The Responsive Neurostimulation System (RNS) has been shown to reduce seizures in patients with focal epilepsy, as demonstrated in a clinical trial where it was more effective than sham (fake) stimulation. This suggests that RNS could potentially help with generalized epilepsy by providing on-demand electrical stimulation to manage seizures. ^{1 2 3 4 5}

Is the Responsive Neurostimulation System generally safe for humans?

The Responsive Neurostimulation System (RNS) is considered a safe alternative for patients with epilepsy who do not respond to medication, though there are risks of implant site infection and bone flap osteomyelitis (infection of the bone). ^{1 3 4 5 6}

How does responsive neurostimulation differ from other treatments for generalized epilepsy?

Responsive neurostimulation (RNS) is unique because it uses a device implanted in the brain to detect and respond to seizure activity with electrical stimulation, unlike traditional treatments that rely on medication. This approach allows for real-time intervention and long-term monitoring of brain activity, providing insights into epilepsy dynamics and potentially improving treatment outcomes. ^{1 3 4 5 7}

Research Team

Martha Morrell, MD

Principal Investigator

NeuroPace, Inc.

Eligibility Criteria

This trial is for individuals aged 12 or older with drug-resistant idiopathic generalized epilepsy who haven't had a neurostimulator implanted. They must have experienced at least two tonic-clonic seizures recently, be on stable seizure medication, and able to attend clinic visits. Women of childbearing age should use reliable contraception.

Inclusion Criteria

Participant does not have a vagus nerve stimulator (VNS, LivaNova) or Participant's VNS is OFF during the two month retrospective baseline and participant is willing to keep the VNS off during the study

I am 12 years old or older.

I have been diagnosed with a type of epilepsy that causes different seizure types.

Exclusion Criteria

You have a device in your brain that uses electricity to work.

I have been diagnosed with severe mental health issues like psychosis or major depression in the last year.

Participant is participating in a therapeutic investigational drug or other device study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Two-month retrospective and one-month prospective baseline period

3 months

Implantation

Participants are implanted with the RNS System and detection is enabled

1 month

Randomization and Blinded Treatment

Participants are randomized to Active or Sham stimulation and are blinded to their group

9 months

Unblinding and Open-label Treatment

Participants are unblinded and those in the Sham group have responsive stimulation enabled

Up to 2 years post-implant

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years post-implant

Treatment Details

Interventions

• RNS System
• Sham stimulation

Trial Overview The RNS System NAUTILUS Study tests the safety and effectiveness of responsive thalamic stimulation as an additional treatment for reducing primary generalized seizures compared to sham (fake) stimulation in participants with drug-resistant epilepsy.

Participant Groups

Group I: Active Group (responsive stimulation ON) Active Control 1 Intervention

Participants are implanted with the RNS System and are receiving treatment with responsive stimulation.

Group II: Sham Group (responsive stimulation OFF) Placebo Group 1 Intervention

Participants are implanted with the RNS System and are not receiving treatment with responsive stimulation.

Who Is Running the Clinical Trial?

NeuroPace

Lead Sponsor

Trials

11

Recruited

1,500+

Findings from Research

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 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 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]

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 NeuroPace RNS System can provide symptomatic relief for patients with drug-resistant partial seizures, but it carries significant risks of implant site infection and bone flap osteomyelitis, as seen in 3 reported cases.

In this study, 10% of patients developed infections related to the RNS device, particularly after multiple battery replacements, highlighting the need for improved techniques to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implant Site Infection and Bone Flap Osteomyelitis Associated with the NeuroPace Responsive Neurostimulation System. Wei, Z., Gordon, CR., Bergey, GK., et al.[2019]

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy. [2022]

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

Implant Site Infection and Bone Flap Osteomyelitis Associated with the NeuroPace Responsive Neurostimulation System. [2019]

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

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