Neurostimulation with RNS System for Epilepsy

(RESPONSE Trial)

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

200 Participants Needed

Trial Summary

What is the purpose of this trial?

To demonstrate that the RNS System is safe and effective as an adjunctive therapy in individuals age 12 through 17 years with medically refractory partial onset epilepsy.

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 data supports the effectiveness of the RNS System treatment for epilepsy?

The RNS System treatment for epilepsy has shown to reduce seizures by 44% in the first year, with improvements to 60-66% in years 3 to 6, without negatively affecting cognition or mood. ^{1 2 3 4 5}

Is the NeuroPace RNS System safe for humans?

The NeuroPace RNS System is considered a safe alternative for patients with epilepsy who do not respond to medication, as it provides on-demand electrical stimulation to reduce seizures without causing neurological harm. ^{1 2 3 4 6}

How does the RNS System treatment for epilepsy differ from other treatments?

The RNS System is unique because it is a brain-responsive neurostimulation device that detects abnormal brain activity and delivers electrical stimulation to prevent seizures, unlike traditional treatments that rely on medication or surgery. It provides continuous monitoring and personalized intervention, offering a non-destructive alternative for patients who do not respond to medication and are not candidates for surgery. ^{1 2 4 6 7}

Research Team

Martha Morrell, MD

Principal Investigator

NeuroPace, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

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

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

Responsive Direct Brain Stimulation for Epilepsy. [2022]

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

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