Electrical Stimulation for Epilepsy

Overseen By Catherine Chu, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Baseline spike ripple rate < 0.5/min

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: 8 weeks

30 Participants Needed

Trial Summary

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 deep brain stimulation (DBS), especially targeting the anterior nucleus of the thalamus and the hippocampus, is safe and effective for treating epilepsy that doesn't respond to medication. This treatment helps reduce seizures by modulating brain circuits and has been supported by strong evidence over the past decade. ^{1 2 3 4 5}

Is electrical stimulation therapy safe for humans?

Research shows that electrical stimulation therapy, like deep brain stimulation (DBS), is generally safe for treating epilepsy, with some risks such as bleeding and infection. Studies support its safety, especially when targeting specific brain areas like the anterior nucleus of the thalamus. ^{1 3 6 7 8}

How is the treatment Open-loop Electrical Stimulation different from other treatments for epilepsy?

Open-loop Electrical Stimulation, also known as Deep Brain Stimulation (DBS), is unique because it involves sending electrical impulses to specific brain areas to reduce seizures, especially in cases where other treatments haven't worked. Unlike some other treatments, it doesn't adjust in real-time to brain activity but has shown significant effectiveness in reducing seizure frequency. ^{1 3 4 5 9}

What is the purpose of this trial?

Open-loop electrical stimulation has been found to reduce spike activity and seizures, but determining the optimal parameters to achieve these effects requires a brute force trial-and-error approach that relies on subjective physician discretion. We will compare the performance of stimulation parameters identified in rodent models to the recommended parameters for neuromodulation used in clinical practice.

Research Team

Catherine J Chu, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals with epilepsy who are currently undergoing intracranial EEG monitoring at Massachusetts General Hospital as part of a presurgical evaluation. Participants must have a certain level of baseline brain activity, specifically more than half a spike ripple per minute.

Inclusion Criteria

Undergoing intracranial EEG investigation at Massachusetts General Hospital during presurgical epilepsy evaluation

Exclusion Criteria

Baseline spike ripple rate < 0.5/min.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo open-loop electrical stimulation to determine optimal parameters for reducing spike activity and seizures

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Open-loop Electrical Stimulation

Trial Overview The study is testing different electrical stimulation settings to see which ones best reduce seizure activity in the brain. It compares optimal parameters from rodent studies against standard clinical neuromodulation settings during open-loop electrical stimulation.

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

Approved in United States as Deep Brain Stimulation (DBS) for:

• Refractory epilepsy
• Focal epilepsy

Approved in European Union as Deep Brain Stimulation (DBS) for:

• Refractory epilepsy
• Focal epilepsy

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Open-loop deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus and the hippocampus has strong evidence supporting its safety and efficacy for treating medically refractory epilepsy, based on a review of 41 studies published since 2008.

Other targets for DBS, while showing some promise, have less robust evidence (Level III and IV), indicating that more research is needed to fully understand their effectiveness and safety in epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-loop deep brain stimulation for the treatment of epilepsy: a systematic review of clinical outcomes over the past decade (2008-present). Zhou, JJ., Chen, T., Farber, SH., et al.[2019]

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]

Deep brain stimulation (DBS) targeting the anterior nucleus of thalamus (ANT) for epilepsy can be effectively visualized using 3 T MRI, allowing for better anatomical delineation of the target area.

There is significant individual variation in the location of ANT among patients, making direct targeting more effective than indirect methods; however, microelectrode recording (MER) alone may not provide reliable localization without detailed imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining the anterior nucleus of the thalamus (ANT) as a deep brain stimulation target in refractory epilepsy: Delineation using 3 T MRI and intraoperative microelectrode recording. Möttönen, T., Katisko, J., Haapasalo, J., et al.[2022]

Deep brain stimulation (DBS) is a safe and effective treatment for refractory epilepsy, as it can modulate brain circuits and reduce the abnormal neuronal activity associated with seizures.

The video outlines the importance of precise surgical planning and targeting of specific brain nuclei (anterior thalamus, centromedian thalamus, and hippocampus) to optimize DBS outcomes, highlighting that each target has unique advantages and challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. de Oliveira, TVHF., Cukiert, A.[2022]

Deep brain stimulation (DBS) is a safe and effective treatment for movement disorders and is increasingly being used for medically refractory epilepsy, showing promise in seizure control.

Recent advancements in understanding epileptogenic networks and improved trial designs have enhanced the evidence supporting DBS for epilepsy, although the exact mechanisms and optimal stimulation parameters are still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the treatment of epilepsy: circuits, targets, and trials. Laxpati, NG., Kasoff, WS., Gross, RE.[2021]

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to significantly reduce seizure frequency in drug-resistant epilepsy, with about 50% of patients experiencing a 46%-90% reduction with ANT-DBS and a 48%-95% reduction with HC-DBS.

Approximately 75% of patients receiving stimulation from ANT, HC, or centromedian nucleus of the thalamus (CMT) report at least a 50% reduction in seizures, with factors like the absence of structural brain abnormalities and specific seizure types influencing the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for drug-resistant epilepsy. Li, MCH., Cook, MJ.[2018]

In a study of 123 patients undergoing deep brain stimulation (DBS) surgery, adverse events (AEs) occurred in 14.6% of cases, but all resolved without permanent effects, indicating a relatively safe profile for the procedure.

The study found that rates of complications such as infections and lead revisions were comparable to existing literature, suggesting that the proposed categories for assessing AEs are effective for evaluating DBS safety and can help in benchmarking against other studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature. Engel, K., Huckhagel, T., Gulberti, A., et al.[2019]

Deep brain stimulation (DBS) has shown efficacy in treating partial seizures in epilepsy, particularly in a recent large, double-blind trial focused on the anterior nucleus of the thalamus, indicating its potential clinical utility.

While DBS is a promising palliative treatment for epilepsy, it carries risks such as hemorrhage and infection, and further research is needed to understand its mechanisms and optimize stimulation parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic brain stimulation for epilepsy. Lockman, J., Fisher, RS.[2018]

Open-loop neocortical electrical stimulation has shown a remarkable average reduction of over 90% in seizure frequency based on reports from 20 patients, indicating its high efficacy in managing intractable epilepsy.

Closed-loop stimulation, studied in a larger cohort of 230 patients, demonstrated a reduction in seizure frequency of 60%-65%, suggesting both methods are effective but raising the need for further comparative studies to determine the preferred approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neocortical electrical stimulation for epilepsy: Closed-loop versus open-loop. Vassileva, A., van Blooijs, D., Leijten, F., et al.[2019]

References

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

Open-loop deep brain stimulation for the treatment of epilepsy: a systematic review of clinical outcomes over the past decade (2008-present). [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Defining the anterior nucleus of the thalamus (ANT) as a deep brain stimulation target in refractory epilepsy: Delineation using 3 T MRI and intraoperative microelectrode recording. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Treatment of Refractory Epilepsy. [2022]

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

Deep brain stimulation for the treatment of epilepsy: circuits, targets, and trials. [2021]

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

Deep brain stimulation for drug-resistant epilepsy. [2018]

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

Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature. [2019]

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

Therapeutic brain stimulation for epilepsy. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Neocortical electrical stimulation for epilepsy: Closed-loop versus open-loop. [2019]