Personalized Electrical Brain Stimulation for Epilepsy

Recruiting at 1 trial location

Overseen By HyeongChan Jo, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Under 18, Pregnant, Prisoners, 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: 5-10 days

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat epilepsy through personalized electrical brain stimulation. The goal is to tailor stimulation based on individual brain activity, improving treatment effectiveness for those unresponsive to current methods. This proof-of-concept study involves patients with implanted electrodes for epilepsy monitoring. Suitable candidates have epilepsy that is difficult to treat with regular medication and already have these monitoring electrodes. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could lead to more effective epilepsy treatments.

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 electrical brain stimulation is safe for epilepsy patients?

Research shows that brain stimulation treatments like the one in this trial are generally safe. Studies indicate that methods such as transcranial direct current stimulation (tDCS) usually do not cause serious side effects or harm to the brain. Most people tolerate these treatments well, and they are considered low risk, even for children.

Additionally, research highlights that each person's unique brain structure can influence how the treatment works. This customization to fit individual needs may enhance safety and effectiveness. Overall, evidence suggests that this type of brain stimulation is safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about model-based electrical brain stimulation for epilepsy because it offers a personalized approach to treatment. Unlike traditional epilepsy treatments, which often rely on medication or non-specific brain stimulation, this method uses real-time data to tailor electrical impulses specifically to the individual's brain activity patterns. This personalized targeting could improve seizure control and reduce side effects compared to more generalized treatments, potentially transforming how epilepsy is managed.

What evidence suggests that this model-based electrical brain stimulation is effective for epilepsy?

Research has shown that electrical stimulation of the brain can help reduce seizures in people with epilepsy. One study found that treatments like transcranial direct current stimulation (tDCS) decreased the number of seizures by 30-40%. These treatments also improved attention and memory. This trial will focus on model-based electrical brain stimulation, using personalized brain models to tailor therapies to each person's unique brain patterns. Overall, evidence suggests that model-based brain stimulation could be a promising way to manage epilepsy. ^{3 4 6 7 8}

Who Is on the Research Team?

Maryam M Shanechi, PhD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults over 18 with epilepsy or brain tumors, who have electrodes already implanted in their brains for clinical monitoring. Participants should be healthy aside from their neurological condition, able to follow instructions, and not part of a vulnerable population like pregnant women or prisoners.

Inclusion Criteria

I am being considered for surgery due to epilepsy or a brain tumor that doesn't respond to medication.

Patients with electrodes implanted based on clinical criteria to locate their seizure focus

Patients with implanted electrode arrays who are willing to participate and able to cooperate and follow research instructions

Exclusion Criteria

I am under 18 years old.

Special classes of subjects such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations

Patients who are unable to give informed consent due to a brain disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo model-based electrical brain stimulation and self-report their symptoms using validated questionnaires

5-10 days

Continuous monitoring during EMU stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Model-based Electrical Brain Stimulation

Trial Overview

The study tests personalized electrical brain stimulation using models based on each patient's neural activity. It aims to improve treatment efficacy by adapting the therapy to individual responses and symptoms tracked via existing iEEG electrodes.

How Is the Trial Designed?

Group I: model-based electrical brain stimulation Experimental Treatment 1 Intervention

Model-based Electrical Brain Stimulation is already approved in European Union, United States for the following indications:

Approved in European Union as Deep Brain Stimulation for:

• Parkinson’s disease
• Essential Tremor
• Epilepsy
• Obsessive-Compulsive Disorder

Approved in United States as Deep Brain Stimulation for:

• Parkinson’s disease
• Essential Tremor
• Epilepsy
• Obsessive-Compulsive Disorder

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 452 electrode implantations in 420 patients with drug-resistant focal epilepsy, subdural electrodes were associated with a significantly higher risk of symptomatic hemorrhages (9.9%) compared to depth electrodes (0.3%).

Despite the higher risk of complications with subdural electrodes, the overall rates of persistent neurological deficits were low (1.3%), indicating that both subdural and depth electrode implantation are generally safe options for intracranial EEG exploration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy. Männlin, J., San Antonio-Arce, V., Reinacher, PC., et al.[2023]

Using a validated neural mass model, researchers identified that electrical stimulation with parameters of membrane polarization greater than 4 mV and frequency over 25 Hz effectively modulates pathological brain activity, particularly in simulating epileptiform activity.

This study supports the use of computational models to optimize stimulation parameters, which could enhance the effectiveness of neuromodulation therapies for conditions like epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of effective stimulation parameters to abort epileptic seizures in a neural mass model. Arrais, M., Wendling, F., Modolo, J.[2020]

A study developed a statistical model of a 24-neuron network to simulate seizure-like activity, allowing for the testing of various neurostimulation patterns.

Using a global optimization algorithm, researchers identified an optimal stimulation pattern that successfully reduced seizures by 92% and prevented the network from entering a seizure state in a closed-loop system, suggesting a new approach to enhance the efficacy of neurostimulation therapies for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression. Sandler, RA., Geng, K., Song, D., et al.[2019]

This study analyzed data from 10 epilepsy patients to develop predictive models of how electrical brain stimulation affects connected brain regions, which could enhance treatment strategies for conditions like epilepsy, Parkinson's disease, and depression.

The research found that a combination of linear and nonlinear modeling best predicts the brain's response to stimulation, suggesting that understanding these dynamics can lead to more effective and tailored stimulation patterns for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of Architectures for Models of Neural Responses to Electrical Brain Stimulation. Steinhardt, C., Sacre, P., Inati, SK., et al.[2020]

Personalized transcranial electric stimulation (tES) can enhance treatment for focal epilepsy by using subject-specific electric field simulations to optimize electrode placement and stimulation parameters, potentially leading to better clinical outcomes.

The proposed workflow incorporates clinical imaging and electroencephalography data to improve the precision of tES, addressing current limitations in electrode targeting and electric field delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized tDCS for Focal Epilepsy-A Narrative Review: A Data-Driven Workflow Based on Imaging and EEG Data. Beumer, S., Boon, P., Klooster, DCW., et al.[2022]

This study measured electric potentials in ten epilepsy patients to understand how transcranial electric stimulation affects the brain, finding that stimulating at 2 mA produces effective cortical electric fields of 0.8 V/m, which aligns with animal study thresholds.

The research validated current-flow models by correlating predicted electric field magnitudes with actual intracranial recordings, establishing a reliable method for targeting brain stimulation in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. Huang, Y., Liu, AA., Lafon, B., et al.[2022]

Intracranial stimulation has been shown to be a safe adjunctive treatment for adults with medically intractable epilepsy, providing proof of principle in clinical studies.

Different stimulation approaches, including both open-loop and closed-loop systems, are being explored, with closed-loop stimulation showing promise by responding to detected epileptiform activity, potentially enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial stimulation therapy for epilepsy. Skarpaas, TL., Morrell, MJ.[2021]

Personalized electrodes (RePE) for transcranial electric stimulation (tES) produce significantly higher electric field strengths in the primary motor and somatosensory cortices compared to non-personalized electrodes (ReNPE), indicating better targeting of these brain regions.

Shifting the position of the ReNPE can enhance electric field distribution, but it still does not match the efficacy of the RePE, highlighting the importance of personalized electrode design for effective brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Computational Model of the Electric Field Distribution due to Regional Personalized or Nonpersonalized Electrodes to Select Transcranial Electric Stimulation Target. Parazzini, M., Fiocchi, S., Cancelli, A., et al.[2017]

The PIMIDES trial focuses on patient-individualized transcranial electric neurostimulation for patients with epilepsy who have a predominant epileptic focus and are resistant to at least two antiepileptic drugs.

This prospective and unblinded study aims to evaluate the safety of subgaleal implantation and the effectiveness of transcranial stimulation in treating pharmacoresistant epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PIMIDES I: a pilot study to assess the feasibility of patient-controlled neurostimulation with the EASEE® system to treat medically refractory focal epilepsy. Kravalis, K., Schulze-Bonhage, A.[2020]

This study measured cranial electrical stimulation (CES) effects in 21 epilepsy patients (16 adults and 5 children) using implanted electrodes, finding a strong correlation between measured and predicted electric fields in the brain, indicating the reliability of personalized simulation models.

The results showed that while increasing stimulation intensity raised voltage levels, the frequency of stimulation did not significantly affect the electric fields, and the arrangement of electrodes was crucial for effective stimulation, highlighting the importance of individualized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo Measurements of Electric Fields During Cranial Electrical Stimulation in the Human Brain. Wang, M., Feng, T., Jiang, H., et al.[2022]

Open-loop electrical cortical stimulation significantly improved seizure control in patients with refractory focal epilepsy, showing a mean reduction of 61% at 1 year, 68% at 2 years, and 80% at 3-7 years post-implantation based on a retrospective study of six patients.

The stimulation was particularly effective in stopping status epilepticus immediately in three patients, leading to long-term seizure reductions of over 90%, with no major procedure-related complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical cortical stimulation for refractory focal epilepsy: A long-term follow-up study. Chang, CW., Lee, ST., Lim, SN., et al.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

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The current meta-analysis on available trials indicates that tDCS can effectively reduce seizure frequency in the short term and is well-tolerated.

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nature.com

nature.com/articles/s41598-024-52355-2

Insights from a model based study on optimizing non ...

This study explores the potential of using TES, to modify the firing pattern of cells in BG that are responsible for motor symptoms in PD.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9133258/

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This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165027025000536

Evaluating the efficacy of non-invasive brain stimulation ...

TMS and tDCS treatments produce a 30–40% seizure reduction effect in addition to attaining enhanced attention and memory functions.

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frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.909421/full

Transcranial current stimulation in epilepsy: A systematic ...

Brain modeling and human studies highlight the influence of individual brain anatomy and physiology on the electric field distribution.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5007190/

Safety of transcranial Direct Current Stimulation: Evidence ...

In this review, tDCS safety indicates the absence of a Serious Adverse Effect including brain tissue injury related to tDCS application. It is necessary to ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X19304966

Safety and tolerability of transcranial magnetic and direct ...

Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk.

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brainstimjrnl.com

brainstimjrnl.com/issue/S1935-861X(24)X0007-8

January-February 2025

Effects of non-invasive brain stimulation over the supplementary motor area on motor function in Parkinson's disease: A systematic review and meta-analysis