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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to use electrical stimulation to reduce seizures in people with epilepsy. Researchers will test different settings for the electrical stimulation to determine which are most effective, comparing findings from animal studies to current medical practices. Ideal participants are those undergoing a specific type of brain monitoring at Massachusetts General Hospital in preparation for epilepsy surgery.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment strategies for 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's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this electrical stimulation is safe for epilepsy?

Research has shown that open-loop electrical stimulation is generally well-tolerated for treating epilepsy. One study found that patients with Lennox-Gastaut Syndrome (LGS) experienced a significant reduction in seizures, with no major safety issues reported. Although these patients did not become completely seizure-free, the treatment reduced their seizures by more than 50%.

Other studies indicate that brain stimulation is safe and effective for conditions like movement disorders, suggesting it might also be safe for epilepsy. Open-loop electrical stimulation is considered relatively safe and may help reduce seizures.

These findings suggest that open-loop electrical stimulation for epilepsy is generally safe. However, as with any treatment, individual experiences may vary. Always discuss potential risks and benefits with healthcare professionals before considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard epilepsy treatments, which often involve medication like anti-seizure drugs, open-loop electrical stimulation offers a non-drug alternative. This technique uses electrical impulses to directly influence brain activity, aiming to reduce seizures without the side effects common in medications. Researchers are excited because this approach targets the brain's electrical patterns more precisely, potentially offering relief for patients who don't respond well to traditional therapies. Additionally, it could provide a more personalized treatment option, as the stimulation can be adjusted to the individual's needs.

What evidence suggests that open-loop electrical stimulation is effective for epilepsy?

Research has shown that open-loop electrical stimulation can help manage epilepsy. One study found that patients with Lennox-Gastaut Syndrome, a type of epilepsy, experienced more than a 50% drop in seizures. Another study found that after two years of treatment, seizures were reduced by nearly 50% on average. These findings suggest that open-loop electrical stimulation might lower the number of seizures for some people with epilepsy. However, results can vary for each person. ^{1 2 3 4 6}

Who Is on the Research Team?

Catherine J Chu, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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]

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]

Citations

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frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.680938/full

Directions of Deep Brain Stimulation for Epilepsy and ...

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pmc.ncbi.nlm.nih.gov

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Brain stimulation treatments in epilepsy: Basic mechanisms ...

All four patients with LGS demonstrated a >50% reduction in seizure frequency (100% response rate), though no patient with LGS achieved seizure freedom [92].

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thejns.org

thejns.org/focus/view/journals/neurosurg-focus/45/2/article-pE5.xml

Open-loop deep brain stimulation for the treatment of epilepsy

In 2008, Lim et al. reported a mean 49.6% reduction in seizures with stimulation (range 35%–61%) at the 2-year follow-up for 4 patients. One patient achieved ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12185915/

Deep Brain Stimulation Therapy for Drug-Resistant Epilepsy

The seminal SANTE trial provided robust evidence of its efficacy, with an initial median seizure reduction of approximately 40.4% observed ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1878747923008760

Deep Brain Stimulation for the Treatment of Epilepsy

Taken together, these data suggest that CMT DBS may be effective for a subset of patients with generalized epilepsy, namely those with Lennox–Gastaut ...

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academic.oup.com/brain/article/148/3/746/7941832

On brain stimulation in epilepsy - Oxford Academic

Given that open-loop stimulation appears relatively safe and may even be anti-ictogenic in its own right, we should not be shy to expedite these clinical ...