Deep Brain Stimulation for Epilepsy

Overseen By Jaison Hampson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Pregnancy, Psychosis, Depression, Low IQ, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Short-term (approximately 20 minutes)

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called deep brain stimulation (DBS) to help people with epilepsy that does not respond to other treatments. Researchers aim to observe how the brain reacts when electrical stimulation targets the thalamus, a key brain area. This study may suit someone diagnosed with epilepsy who already uses a device like DBS or RNS and visits an epilepsy clinic regularly. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research in epilepsy treatment.

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's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this device is safe for epilepsy?

Research has shown that both RNS (Responsive Neurostimulation) and DBS (Deep Brain Stimulation) are generally safe for treating epilepsy. One study found that RNS significantly reduced seizures over nine years and was considered safe. Another study demonstrated that both DBS and RNS led to a similar decrease in seizures, indicating they are well-tolerated. Most side effects can be managed, and many patients experience a meaningful reduction in seizures. However, the effectiveness of these treatments can vary from person to person. Overall, these treatments have been safely used in many patients, including both adults and children. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation (DBS) for epilepsy because it offers a unique approach compared to current treatments like anti-seizure medications and vagus nerve stimulation. Unlike these options, which either control seizures through medication or by sending electrical signals to the vagus nerve, DBS targets specific areas in the brain directly responsible for seizure activity. This precise targeting could lead to more effective seizure control with potentially fewer side effects. With DBS, there’s hope for improved quality of life for those whose seizures are not well-managed by existing treatments.

What evidence suggests that RNS/DBS activation is effective for epilepsy?

Research has shown that brain-responsive neurostimulation (RNS) systems can greatly reduce seizures in people with epilepsy. One study found a 75% reduction in seizures after nine years of treatment, with 73% of patients responding well. Another study reported that 68.2% of children experienced more than a 50% reduction in seizures after one year. This trial will evaluate the effectiveness of RNS/DBS activation, which includes both deep brain stimulation (DBS) and RNS, as previous studies have shown similar results in reducing seizures. While results can vary, these treatments generally lead to significant improvements for many patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Sandipan Pati, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with intractable epilepsy who are already receiving neuromodulation therapy (like DBS or RNS) and are monitored at an outpatient epilepsy clinic. It's not suitable for pregnant women, those with recent severe mental health issues, an IQ below 70, or anyone unwilling to share their medical records for research.

Inclusion Criteria

I am receiving therapy with an implanted device for nerve stimulation.

I have been diagnosed with epilepsy.

Followed in the outpatient epilepsy clinic

Exclusion Criteria

Do not agree to share their medical records for research purposes

Pregnant women

Intelligence quotient (IQ) less than 70 as measured by clinical neuropsychological evaluation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive thalamic electrical stimulation to map cortical evoked responses

Short-term (approximately 20 minutes)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RNS/DBS activation

Trial Overview The study aims to understand the immediate brain response to thalamic electrical stimulation provided by implanted devices in patients with difficult-to-treat epilepsy. This could help improve therapeutic outcomes of deep brain stimulation.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

RNS/DBS activation is already approved in United States, European Union for the following indications:

Approved in United States as RNS System for:

• Partial-onset seizures with one or two seizure onset zones in adults with epilepsy who have not been controlled with two or more antiepileptic drugs

Approved in United States as DBS Therapy for:

• Focal seizures in adults with epilepsy who have not been responsive to two or more antiepileptic drugs and could not be treated with other types of epilepsy surgery

Approved in European Union as DBS Therapy for:

• Refractory epilepsy in adults

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study involving 8 patients with intractable epilepsy, the orthogonal approach for placing responsive neurostimulation (RNS) electrodes showed no complications, indicating a high level of safety during the procedure.

Among the patients followed for at least one year, one became seizure-free and two had over 50% reduction in seizures, suggesting that this method may be effective in managing epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic Orthogonal Implantation of Responsive Neurostimulation (RNS) Depth Electrodes in the Mesial Temporal Lobe: Case Series. Chan, AY., Tran, DK., Paff, MR., et al.[2021]

Responsive neurostimulation (RNS) directly targets seizure foci using electrocorticography (ECoG) patterns, making it a promising option for patients with drug-resistant epilepsy who cannot undergo surgery.

Other devices like the AspireSR vagal nerve stimulator and deep brain stimulation of the anterior thalamus show similar efficacy in managing intractable epilepsy, highlighting the potential of various stimulation techniques in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive brain stimulation in epilepsy. Hartshorn, A., Jobst, B.[2023]

The RNS® System is the first device that provides closed-loop brain stimulation, approved by the FDA in 2013 for patients with drug-resistant partial onset seizures, demonstrating its safety and effectiveness in a 2-year pivotal study.

The device works by continuously monitoring brain activity and delivering electrical stimulation when abnormal activity is detected, and it is currently being studied for long-term safety and effectiveness over an additional 7 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The RNS System: responsive cortical stimulation for the treatment of refractory partial epilepsy. Sun, FT., Morrell, MJ.[2014]

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, which uses closed-loop responsive neurostimulation, significantly reduces the frequency of disabling seizures in adults with medically intractable focal seizures, achieving median reductions of 75% after 9 years of treatment.

This treatment is well tolerated and not only improves seizure control but also enhances quality of life and cognitive function, while providing valuable data for ongoing epilepsy management and research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain-responsive neurostimulation for epilepsy (RNS® System). Skarpaas, TL., Jarosiewicz, B., Morrell, MJ.[2019]

In a long-term study of over 245 patients with epilepsy, responsive neural stimulation (RNS) showed that 16% of patients became seizure-free, while 60% experienced a reduction of 50% or more in their seizures, indicating its efficacy as an adjunct therapy.

Additionally, 44% of patients reported an improvement in their quality of life by the end of the second year, suggesting that RNS not only helps reduce seizures but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrostimulation for Refractory Epilepsy: A Review. Shenoy, C., Aodah Alzahrani, H., Upton, AR., et al.[2018]

A review of the Manufacturer and User Facility Device Experience (MAUDE) database identified 241 unique complications related to responsive neurostimulation (RNS) for epilepsy, with the most common issues being infections (40%) and lead breaks (12%).

Over half of the reported complications (67%) required surgical intervention for device revision or removal, highlighting the need for improved infection prevention strategies and better patient counseling regarding potential risks associated with the RNS system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Intracranial Responsive Neurostimulation Devices for Epilepsy Through a Retrospective Analysis of the Federal MAUDE Database. Giles, TX., Bennett, J., Stone, CE., et al.[2022]

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]

A 35-year-old man experienced severe cerebral vasospasm and a stroke following the implantation of a Responsive Neurostimulation (RNS) device for drug-resistant epilepsy, highlighting a rare but serious complication associated with this treatment.

Despite treatment improving the vasospasm, the patient developed a thrombus requiring mechanical thrombectomy, leading to residual cognitive and motor deficits, emphasizing the need for awareness of this potential risk in RNS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasospasm secondary to responsive neurostimulator placement: a previously unreported complication. Illustrative case. Rogowski, B., Miller, A., Saway, BF., et al.[2023]

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 study evaluated 14 patients with RNS System depth leads implanted in the thalamus, finding that these leads successfully detected and terminated epileptiform activity, indicating their efficacy in managing seizures.

Thalamic leads, whether used alone or in combination with cortical leads, effectively prevented the propagation of electrographic seizures, making them a promising option for patients with intractable epilepsy who cannot undergo surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsive Neurostimulation Targeting the Anterior, Centromedian and Pulvinar Thalamic Nuclei and the Detection of Electrographic Seizures in Pediatric and Young Adult Patients. Beaudreault, CP., Muh, CR., Naftchi, A., et al.[2022]

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]

Citations

1. 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.

2. 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 ≥ ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301944X

Neurostimulation treatments for epilepsy: Deep brain ... Twenty-two of the 27 patients had seizure outcome data at one year, and 15 out of 22 children (68.2 ​%) achieved a greater than 50 ​% reduction in seizure ...

4. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1429223/full

The comparison of DBS and RNS for adult drug-resistant ... There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS ...

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 ...