Personalized Electrical Brain Stimulation for Epilepsy

Recruiting at 1 trial location

Overseen By Omid G Sani, 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

Trial Summary

What is the purpose of this trial?

Neuropsychiatric disorders are a leading cause of disability worldwide with depressive disorders being one of the most disabling among them. Also, millions of patients do not respond to current medications or psychotherapy, which makes it critical to find an alternative therapy. Applying electrical stimulation at various brain targets has shown promise but there is a critical need to improve efficacy. Given inter- and intra-subject variabilities in neuropsychiatric disorders, this study aims to enable personalizing the stimulation therapy via i) tracking a patient's own symptoms based on their neural activity, and ii) a model of how their neural activity responds to stimulation therapy. The study will develop the modeling elements needed to realize a model-based personalized closed-loop system for electrical brain stimulation to achieve this aim. The study will provide proof-of-concept demonstration in epilepsy patients who already have intracranial electroencephalography (iEEG) electrodes implanted for their standard clinical monitoring unrelated to this study, and who consent to being part of the study.

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 data supports the effectiveness of this treatment for epilepsy?

Research shows that personalized electrical brain stimulation can effectively modulate brain activity in epilepsy by using specific stimulation parameters, such as a membrane polarization greater than 4 mV and a frequency over 25 Hz. Additionally, personalized models can predict the effects of stimulation, helping to optimize treatment for individual patients. ^{1 2 3 4 5}

Is personalized electrical brain stimulation safe for humans?

Research shows that various forms of electrical brain stimulation, including intracranial and transcranial methods, have been studied for epilepsy and other conditions, demonstrating a good safety profile in both short-term and long-term studies. ^{4 6 7 8 9}

How is the Personalized Electrical Brain Stimulation treatment different from other epilepsy treatments?

This treatment is unique because it uses personalized electrical brain stimulation, which is tailored to each patient's specific brain activity patterns to effectively reduce seizures. Unlike standard treatments, it involves optimizing stimulation parameters using computational models and patient-specific data to target the exact brain areas involved in epilepsy. ^{1 3 8 10 11}

Research Team

Maryam M Shanechi, PhD

Principal Investigator

University of Southern California

Eligibility Criteria

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

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

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

Identification of effective stimulation parameters to abort epileptic seizures in a neural mass model. [2020]

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

Investigation of Architectures for Models of Neural Responses to Electrical Brain Stimulation. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Personalized tDCS for Focal Epilepsy-A Narrative Review: A Data-Driven Workflow Based on Imaging and EEG Data. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

In vivo Measurements of Electric Fields During Cranial Electrical Stimulation in the Human Brain. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Electrical cortical stimulation for refractory focal epilepsy: A long-term follow-up study. [2019]

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

Intracranial stimulation therapy for epilepsy. [2021]

8. England 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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy. [2023]

10. United States 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. [2017]

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

Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression. [2019]