Brain Stimulation for Epilepsy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Barbara Jobst

Disqualifiers: Recent RNS® implant

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how brain stimulation affects memory in people with epilepsy. It focuses on individuals with an implanted device, the RNS® Neurostimulator, to help control seizures. Researchers seek to determine how this device influences brain activity related to memory. The trial targets individuals with epilepsy who have had the device for over three months and experience seizures not well-controlled by medication. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance memory-related outcomes for others with epilepsy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this brain stimulation technique is safe for epilepsy patients?

Research has shown that the RNS® Neurostimulator is generally safe for people with epilepsy. Data collected over nine years indicate that patients tolerate this device well. Studies have demonstrated its safety in controlling seizures, particularly for those unresponsive to medication. The FDA has approved the device for treating focal seizures, which begin in a specific area of the brain, confirming its safety for this use.

Even for children as young as six, the neurostimulator has proven safe and practical when the seizure's origin in the brain is identified. Overall, many patients with drug-resistant epilepsy have safely used the RNS® Neurostimulator. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the RNS® Neurostimulator for epilepsy because it offers a novel approach by directly targeting the brain's electrical activity, which is different from standard treatments like anti-seizure medications. Unlike medications that work chemically to stabilize brain activity, this device uses electrical stimulation to modulate neural circuits, potentially reducing seizures in patients who don't respond to drugs. This personalized intervention can be continuously adjusted based on real-time data from the brain, offering a tailored treatment option that could improve quality of life for those with pharmaceutically intractable seizures.

What evidence suggests that this brain stimulation is effective for epilepsy?

Research has shown that the RNS® Neurostimulator, which participants in this trial may receive, can greatly reduce seizures in people with epilepsy. Studies indicate that after one year of using the RNS system, seizures typically decrease by 67%. By two years, this reduction often improves to 75%. Over a longer period, such as nine years, about 73% of patients experience a significant drop in seizures. Some research suggests that the system is effective for various age groups, including older adults. Overall, the RNS system shows promise, especially for those who haven't found relief with medications. ^{3 6 7 8 9}

Who Is on the Research Team?

Barbara Jobst, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with epilepsy who have had an RNS® device implanted for at least 3 months. Participants must be able to consent and complete tasks as judged by the lead researcher.

Inclusion Criteria

Able to give informed consent

I have been diagnosed with epilepsy.

I can do the tasks required for the study, as per the lead researcher.

Exclusion Criteria

I had an RNS Neurostimulator implanted less than 3 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo therapeutic stimulation for epilepsy and memory tasks using the RNS® Neurostimulator

4 weeks

Multiple sessions for memory and navigation tasks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Electrical Stimulation

Trial Overview

The study examines how brain activity linked to good memory functions in people with epilepsy using ECoG data from those with an RNS® device during memory and navigation tasks.

How Is the Trial Designed?

Group I: RNS® Neurostimulator Experimental Treatment 1 Intervention

Subjects with pharmaceutically intractable seizures who have been implanted with a RNS® Neurostimulator.

Electrical Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Electrical Stimulation for:

• Pain relief
• Muscle strengthening
• Rehabilitation after injury or surgery
• Neurological disorders
• Wound healing

Approved in European Union as Electrical Stimulation for:

• Pain management
• Muscle rehabilitation
• Neurological conditions
• Wound care

Approved in Canada as Electrical Stimulation for:

• Chronic pain
• Muscle atrophy
• Neurological rehabilitation
• Wound healing

Who Is Running the Clinical Trial?

Barbara Jobst

Lead Sponsor

Trials

1

Recruited

20+

NeuroPace

Industry Sponsor

Trials

11

Recruited

1,500+

Published Research Related to This Trial

In a study involving 20 healthy males, neuromuscular electrical stimulation (NMES) led to a significant decrease in maximal voluntary contraction (MVC) torque after just one sequence, indicating early onset of neuromuscular fatigue.

Cortical activity in both the primary motor (M1) and primary somatosensory (S1) areas declined during NMES, suggesting that the motor cortex is involved in the loss of force, but the decrease in motor output is not due to increased inhibition from the sensory cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical motor output decreases after neuromuscular fatigue induced by electrical stimulation of the plantar flexor muscles. Alexandre, F., Derosiere, G., Papaiordanidou, M., et al.[2015]

Neuroprostheses (NPs) have evolved from early muscle stimulators to advanced devices that can effectively activate paralyzed muscles, with functional electrical stimulation (FES) showing significant benefits in enhancing muscle function, particularly in conditions like foot drop.

Recent advancements in technology have made these devices more convenient and reliable, leading to improved therapeutic outcomes, although challenges remain in enhancing upper limb function compared to lower limbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor Neuroprostheses. Prochazka, A.[2019]

A study involving 713 chronic pain patients showed that fixed-site high-frequency transcutaneous electrical nerve stimulation (FS-TENS) significantly reduced pain intensity and interference with daily activities and mood after 60 days of use.

The effectiveness of FS-TENS improved with increased usage, with 57.1% of high-utilization users experiencing clinically meaningful reductions in pain interference, highlighting the importance of consistent application for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of fixed-site high-frequency transcutaneous electrical nerve stimulation in chronic pain: a large-scale, observational study. Kong, X., Gozani, SN.[2022]

Recent research highlights that electrical stimulation of motor nerves can enhance muscle strength, reduce muscle spasms, and help manage spasticity, making it a valuable tool in physiotherapy.

Functional electrical stimulation (F.E.S.) is gaining traction as a key component in rehabilitation programs for patients with neurological impairments, suggesting its potential for broader application in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor stimulation with interferential currents. DE Domenico, GG., Strauss, GR.[2014]

A systematic review of literature on neuromuscular electrical stimulation (NMES) identified effective stimulation parameters for treating muscle impairments in conditions like stroke, ACL reconstruction, and knee osteoarthritis, based on a consensus among six Canadian PT experts.

The article serves as a comprehensive resource for physiotherapists, offering evidence-based recommendations and safety tips for the effective application of NMES in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular Electrical Stimulation for Treatment of Muscle Impairment: Critical Review and Recommendations for Clinical Practice. Nussbaum, EL., Houghton, P., Anthony, J., et al.[2019]

The study introduces a real-time functional electrical stimulation (FES) system that uses electromyography (eEMG) signals to predict joint torque, which is crucial for personalized rehabilitation in spinal cord injury (SCI) patients.

Testing on 3 able-bodied subjects and 3 SCI patients showed that both the Kalman filter and recurrent neural network (RNN) methods effectively estimated joint torque, with RNN being more computationally efficient, indicating potential for practical use in personalized neuroprosthetic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time estimation of FES-induced joint torque with evoked EMG : Application to spinal cord injured patients. Li, Z., Guiraud, D., Andreu, D., et al.[2019]

Vagus nerve stimulation is the only method of electrical stimulation for epilepsy that has undergone large, controlled clinical trials, showing its potential as a therapy for intractable epilepsy.

Other forms of electrical stimulation, such as targeting the anterior nuclei of the thalamus and cortical stimulation, are still in the trial phase and are considered experimental, indicating that more research is needed to establish their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Electrical Stimulation Therapy for Epilepsy. Oommen, J., Morrell, M., Fisher, RS.[2022]

Brain stimulation techniques, such as responsive neurostimulation and advanced vagus nerve stimulation, are being used to help epilepsy patients who do not respond well to medications, targeting either the seizure origin or key brain areas to reduce seizure severity.

While new transcutaneous stimulation methods are emerging, their effectiveness is still uncertain, highlighting the need for careful evaluation of different neuromodulatory strategies in treating epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation as a neuromodulatory epilepsy therapy. Schulze-Bonhage, A.[2017]

Extraneural electrodes are more stable for long-term use compared to intraneural electrodes, which is important for the safety of chronic electrical stimulation applications.

Current guidelines suggest that chronic stimulation should be kept below 30 Hz and effective stimulation time below 50% to minimize risks, but more comprehensive data is needed to establish safe stimulation protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of long-term electrical peripheral nerve stimulation: review of the state of the art. Günter, C., Delbeke, J., Ortiz-Catalan, M.[2021]

In a study involving 10 adults, neuromuscular electrical stimulation (NMES) with a 200-microsecond pulse duration allowed participants to tolerate significantly greater muscle torques compared to a 50-microsecond pulse duration, indicating enhanced efficacy for muscle strengthening.

The findings suggest that medium pulse durations may be more effective for maximizing muscle torque responses, despite the common belief that shorter pulses are preferable due to lower pain thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of maximum tolerated muscle torques produced by 2 pulse durations. Scott, WB., Causey, JB., Marshall, TL.[2014]

Citations

1.

neurology.org

neurology.org/doi/10.1212/WNL.0000000000010154

Nine-year prospective efficacy and safety of brain- ...

At the completion of 9 years of treatment, the median percent seizure reduction was 75%, the responder rate was 73%, and more than one-third of patients had a ≥ ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2589986425000346

Responsive neurostimulation for patients with refractory ...

Meta-analysis of 207 patients supports RNS efficacy in refractory MTLE; RNS therapy may reduce seizure frequency in patients with refractory MTLE; Some patients ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8633477/

The Efficacy, Safety, and Outcomes of Brain‐responsive ...

Our study suggests that older adults treated with the RNS System achieve seizure outcomes comparable to younger adults.

4.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1240380/full

Clinical outcomes following responsive neurostimulation ...

Subsequent real-world experience with RNS has demonstrated median seizure frequency reduction of 67% at 1 year and 75% at 2 years. Responder ...

5.

nature.com

nature.com/articles/s43856-023-00401-x

Unearthing the mechanisms of responsive ... - Nature

In clinical trials, RNS therapy results in a meaningful reduction in median seizure frequency, but the response is highly variable across ...

6.

neuropace.com

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

RNS System | Proven Safety Profile

Responsive neurostimulation was well tolerated and safe over time. Conclusions from 9 years of data in the largest prospective neuromodulation study in the ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1059131123003205

Safety & feasibility of responsive neurostimulation in ...

RNS is a feasible and safe option for children as young as six years with refractory epilepsy when appropriate seizure focus identification has been performed.

8.

my.clevelandclinic.org

my.clevelandclinic.org/health/procedures/responsive-neurostimulation

Responsive Neurostimulation (RNS) - Cleveland Clinic

The U.S. Food and Drug Administration (FDA) approved RNS to treat seizures that start in one part of the brain (focal seizures) and don't respond to other ...

9.

reports.mountsinai.org

reports.mountsinai.org/article/neuro2021-06-responsive-neurostimulation-in-pediatric-patients

Examining the Safety of Responsive Neurostimulation ...

Mount Sinai researchers demonstrate safety and efficacy of responsive neurostimulation for pediatric patients with medically refractive epilepsy.