Neurostimulation with RNS System for Epilepsy

(RESPONSE Trial)

No longer recruiting at 2 trial locations

Overseen By Sharon McFadden

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: NeuroPace

Must be taking: Anti-seizure medications

Must not be taking: Chronic anticoagulants

Disqualifiers: Generalized seizures, Active psychosis, Major depression, Suicidal ideation, 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)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device called the RNS System (Responsive Neurostimulation System) to determine its safety and effectiveness in helping young people with challenging epilepsy. The focus is on children and teens, aged 12 to 17, who experience seizures difficult to control with regular medication. Participants should have seizures that disrupt daily activities like work or mobility and have tried at least two anti-seizure medications without success. The trial includes an evaluation group that will have the RNS System implanted and receive stimulation. For those with partial-onset epilepsy not well-managed with drugs, this trial might be suitable. As an unphased trial, this study offers a unique opportunity to explore a new treatment option for epilepsy that existing medications have not well-managed.

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

The trial information does not specify if you need to stop taking your current medications. However, since the trial is for those who have not responded to at least two anti-seizure medications, you may be able to continue your current treatment. Please consult with the trial team for specific guidance.

What prior data suggests that the RNS System is safe for individuals with epilepsy?

Research has shown that the RNS System, used for treating epilepsy, is safe. Individuals with this system have a lower risk of sudden unexpected death in epilepsy (SUDEP) compared to those without it. This is significant because SUDEP poses a serious risk for people with epilepsy.

The RNS System has undergone thorough study. Participants using this device did not experience unusual or dangerous side effects, indicating it is well-tolerated.

Overall, evidence suggests that the RNS System is safe for people with epilepsy and could serve as a new option for those who haven't found success with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The RNS System is unique because it offers a responsive neurostimulation approach for epilepsy, unlike standard treatments like medications and surgery. Most current treatments focus on preventing seizures through medication or removing the part of the brain where seizures originate. However, the RNS System continuously monitors brain activity and delivers electrical stimulation only when abnormal activity is detected, potentially minimizing side effects and improving seizure control. Researchers are excited about this treatment because it represents a personalized and dynamic method that adapts to the patient’s brain activity in real-time, offering hope for those who have not found success with traditional therapies.

What evidence suggests that the RNS System is effective for epilepsy?

Research has shown that the RNS System can help reduce seizures in people with drug-resistant focal epilepsy. One study found that adults experienced 62% fewer seizures within the first six months of using the RNS System. Another study reported a 44% decrease in seizures after one year, which improved to 53% after two years. Long-term data indicated a 75% reduction in seizure frequency over nine years. In this trial, participants in the evaluation group will have an RNS System implanted and receive responsive stimulation. These results suggest that the RNS System could significantly help manage seizures in people with hard-to-treat epilepsy. ^{2 3 4 6 7}

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 young individuals aged 12-17 with medically refractory partial onset epilepsy. They must have regular, countable seizures and not be pregnant or using certain medications. Participants need to commit to clinic visits, maintain a seizure diary, and have failed at least two anti-seizure drugs.

Inclusion Criteria

Subject and/or parent/guardian must be willing and able to provide informed consent and assent when appropriate.

You have had medical tests that showed you have no more than two areas in your brain that can cause seizures.

I or my caregiver can reliably count and describe my distinct seizures.

Exclusion Criteria

Subject is pregnant.

You have a device in your brain that sends electrical energy.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Monitoring

Participants undergo implantation of the RNS System and initial monitoring for device-related adverse events

12 weeks

Regular visits for monitoring

Treatment

Participants receive responsive stimulation with the RNS System

12 months

Monthly visits for device adjustment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Quarterly visits for ongoing assessment

What Are the Treatments Tested in This Trial?

Interventions

• RNS System

Trial Overview The RNS System RESPONSE Study is testing the safety and effectiveness of the RNS System as an additional treatment for epilepsy in adolescents. The study involves surgical implantation of this neurostimulator device.

How Is the Trial Designed?

Group I: Evaluation Group (stimulation ON) Experimental Treatment 1 Intervention

Group of participants that have an RNS System implanted and are being treated with responsive stimulation.

Who Is Running the Clinical Trial?

NeuroPace

Lead Sponsor

Trials

11

Recruited

1,500+

Published Research Related to This Trial

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]

The RNS® System offers a promising treatment for patients with refractory partial onset seizures, achieving a 44% reduction in seizures at one year, which improves to 60-66% over three to six years.

This closed-loop brain stimulation method does not negatively affect cognitive function or mood, and the risks associated with the device are comparable to those of other implanted medical devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive Direct Brain Stimulation for Epilepsy. Morrell, MJ., Halpern, C.[2022]

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]

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]

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. neuropace.com neuropace.com/blog/epilepsy-treatment-rns-system-epilepsy-research-post-approval-study/

Epilepsy Treatment Results with the RNS System New study shows the RNS System helps reduce seizures by 62% within the first 6 months in adults with drug-resistant focal epilepsy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4233950/

Final results of the RNS System Pivotal trial - PMC The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time ( ...

3. neuropace.com neuropace.com/wp-content/uploads/2025/04/AANPlatformPAS2025_FINAL_footnote.pdf

Multicenter Post-Approval Study of the RNS System in ... Effectiveness Conclusions Based on 3-Year Results. RNS System therapy is observed to be effective for all types of focal epilepsy. • Efficacy ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000212230

Multicenter Post-approval Study of the RNS System in ... Data from 255 participants were included in the primary effectiveness endpoint. The reduction in seizures overall was 82% (1st quartile 100%; 3 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8083819/

Evidence of state-dependence in the effectiveness ... In clinical trials, RNS System treatment results in median seizure frequency reduction of 75% after nine years [1,2]. However, therapeutic ...

6. neuropace.com neuropace.com/providers/rns-system-safety-data/

RNS System | Proven Safety Profile Patients treated with the RNS System have a statistically significantly lower rate of SUDEP than a comparable refractory population.1. Read More About Lower ...

7. neuropace.com neuropace.com/patients/neuropace-rns-system/

NeuroPace RNS System | Focal Epilepsy Treatment Device 35% of patients achieved ≥ 90% seizure frequency reduction*; 28% of patients had at least one ≥ 6 month period with no seizures. *during last 6 months of follow ...