Brain Stimulation for Epilepsy

Overseen By Izzie Meunier

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must be taking: Anti-seizure medicines

Disqualifiers: Psychogenic seizures, Psychiatric hospitalization, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether electrical stimulation on the scalp can reduce the number and severity of seizures in people with epilepsy. It uses a device called ActivaDose II to deliver low (0.1 mA) or high (2.0 mA) levels of transcranial direct current stimulation (tDCS) to determine which is more effective. Ideal participants have epilepsy that isn't well-managed by medication and experience at least two seizures per month. As an unphased trial, this study offers patients a unique opportunity to explore a novel approach to managing their epilepsy.

Will I have to stop taking my current medications?

No, you don't have to stop taking your current medications. You need to keep your medication the same during the study, but rescue meds are allowed.

What prior data suggests that transcranial direct current stimulation (tDCS) is safe for epilepsy treatment?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe and well-tolerated for people with drug-resistant epilepsy. Studies indicate that tDCS can effectively reduce seizures without causing serious side effects.

Patients using the low-level ActivaDose II 0.1 mA typically do not experience significant problems. Mild side effects may include slight skin irritation where the device is applied.

For the higher-level ActivaDose II 2.0 mA, similar safety has been reported. Although some unrelated health events, such as deaths and hospitalizations, occurred, they were not connected to the tDCS treatment. The higher dose is also considered safe, with improvements in seizure activity noted soon after treatment.

Overall, both treatment options show promise in managing seizures with minimal side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial direct current stimulation (tDCS) for epilepsy because it offers a non-invasive way to modulate brain activity, unlike traditional anti-seizure medications that often involve systemic side effects. While standard treatments like anticonvulsant drugs work by stabilizing electrical activity in the brain, tDCS uses a mild electrical current applied to the scalp to directly influence neuronal excitability. This method has the potential to reduce seizure frequency with minimal side effects, making it a promising alternative or complementary option for individuals whose epilepsy isn't well-controlled by medication alone. Furthermore, the ability to adjust the intensity of the stimulation, as seen with the low (0.1 mA) and high (2.0 mA) amplitude options, allows for personalized treatment plans tailored to patient needs.

What evidence suggests that this trial's treatments could be effective for epilepsy?

Research shows that transcranial direct current stimulation (tDCS) can help reduce seizures in people with epilepsy. In this trial, participants will receive either a low-level treatment (0.1 mA) or a higher-level treatment (2.0 mA) of tDCS. Previous studies have shown that using tDCS at 0.1 mA lowered the number of seizures by about 28% after one month and 49% after two months, indicating a significant drop in seizures over time. Another study found that a higher-level treatment (2.0 mA) improved seizure activity and reduced the number of seizures in just one day, although results varied depending on other factors. Overall, these studies suggest that tDCS, whether at 0.1 mA or 2.0 mA, may help control seizures in people with epilepsy, especially for those who do not respond well to medications. ^{1 2 5 6 7}

Who Is on the Research Team?

Brian Lundstrom, MD, PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with focal epilepsy who experience at least two seizures per month and haven't found seizure control with at least two anti-seizure medications. Participants must be able to maintain their current medication regimen, understand consent in English, and keep a seizure diary.

Inclusion Criteria

You have at least two seizures every month that can be counted.

You have not been able to manage seizures with at least two different seizure medications.

Able to maintain a constant medication for duration of the study (rescue meds allowed).

Exclusion Criteria

Your illness is expected to get worse during the study.

You have seizures that are not caused by epilepsy.

You have tried to harm yourself or been in a psychiatric hospital in the past 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment A (Low Amplitude)

Subjects receive low amplitude tDCS treatment for 2 months

2 months

Treatment B (High Amplitude)

Subjects receive high amplitude tDCS treatment for 2 months

2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• ActivaDose II 0.1 mA transcranial direct current stimulation (tDCS)
• ActivaDose II 2.0 mA transcranial direct current stimulation (tDCS)

Trial Overview The study tests whether electrical stimulation applied to the scalp using ActivaDose II device can reduce the frequency and intensity of epileptic seizures. There are two levels of stimulation being tested: low (0.1 mA) and standard (2.0 mA).

How Is the Trial Designed?

Group I: tDCS Treatment B (High Amplitude) Experimental Treatment 1 Intervention

Subjects with focal epilepsy that is not well-controlled on anti-seizure medications will receive 2 different treatments periods, each lasting 2 months, of transcranial direct current stimulation (tDCS). The last treatment stimulation will be completed during the following 2-months.

Group II: tDCS Treatment A (Low Amplitude) Experimental Treatment 1 Intervention

Subjects with focal epilepsy that is not well-controlled on anti-seizure medications will receive 2 different treatments periods, each lasting 2 months, of transcranial direct current stimulation (tDCS). The initial treatment stimulation will be completed during the first 2-months.

ActivaDose II 0.1 mA transcranial direct current stimulation (tDCS) is already approved in United States, European Union for the following indications:

Approved in United States as ActivaDose II for:

• Epilepsy
• Focal Status Epilepticus

Approved in European Union as ActivaDose II for:

• Epilepsy
• Focal Status Epilepticus

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

Cathodal transcranial direct current stimulation (tDCS) at 100 microA for 60 minutes significantly increased the threshold for localized seizure activity in rats, lasting over 2 hours, indicating its potential as an anticonvulsant treatment.

Higher intensity cathodal tDCS at 200 microA for just 30 minutes also produced a similar lasting effect, while anodal tDCS did not show any significant impact, suggesting that the efficacy of tDCS in epilepsy may depend on the polarity and strength of the stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the rat cortical ramp model of focal epilepsy. Liebetanz, D., Klinker, F., Hering, D., et al.[2022]

Cathodal transcranial direct current stimulation (tDCS) significantly reduced convulsions by 21% and protected against hippocampal cell loss in immature rats following status epilepticus, suggesting its potential as a neuroprotective treatment.

The tDCS treatment not only decreased seizure activity but also improved cognitive performance in spatial learning tasks, indicating its efficacy in addressing both seizure control and cognitive impairment after brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats. Kamida, T., Kong, S., Eshima, N., et al.[2022]

Transcranial direct current stimulation (tDCS) is a noninvasive method that can significantly alter cortical excitability by shifting the resting membrane potential of neurons, with anodic stimulation increasing and cathodic stimulation decreasing excitability.

The effects of tDCS can last beyond the stimulation period, depending on the duration and intensity of the stimulation, suggesting its potential for therapeutic applications in neuropsychiatric conditions, though further clinical studies are needed to evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modulation of cortical excitability by transcranial direct current stimulation]. Nitsche, MA., Liebetanz, D., Tergau, F., et al.[2019]

Transcranial direct current stimulation (tDCS) has shown preliminary safety and efficacy in reducing epileptic seizures in both animal studies and clinical trials involving 65 human participants, with 67% of studies reporting effective seizure reduction.

All patients tolerated tDCS well, indicating a favorable safety profile, but further research is needed to establish optimal stimulation protocols and assess long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Epilepsy. San-Juan, D., Morales-Quezada, L., Orozco Garduño, AJ., et al.[2018]

Transcranial direct current stimulation (tDCS) significantly reduced interictal spike counts in rats with chronic seizures immediately after treatment, suggesting its potential efficacy in modulating epileptic activity.

The study found that enhanced delta oscillations during tDCS may underlie its inhibitory effects on seizure excitability, while changes in BDNF protein expression indicate a complex interaction between tDCS and neural mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures. Wu, YJ., Chien, ME., Chiang, CC., et al.[2022]

In a study involving 15 healthy males, different electrode montages for transcranial direct current stimulation (tDCS) were tested, but no significant changes in corticospinal excitability (CSE) were observed across all four types of tDCS (conventional and high-definition) administered.

Interestingly, while conventional tDCS reduced intra-individual variability in responses, high-definition tDCS resulted in increased variability, suggesting that further research is needed to optimize the parameters for effective use of HD-tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcranial direct current stimulation on corticospinal and cortico-cortical excitability and response variability: Conventional versus high-definition montages. Pellegrini, M., Zoghi, M., Jaberzadeh, S.[2021]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

In a study of 12 patients with drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis, cathodal transcranial direct current stimulation (tDCS) significantly reduced seizure frequency from an average of 10.58 to 1.67 seizures per month (p=0.003).

Eighty-three percent of patients experienced more than a 50% reduction in seizures after tDCS, with 50% becoming seizure-free for one month, indicating that tDCS could be a promising additional treatment option for patients awaiting or rejecting surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Tekturk, P., Erdogan, ET., Kurt, A., et al.[2019]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11586187/

Transcranial direct current stimulation in the management ... Our results indicated that tDCS reduced seizure frequency by ~28 and 49% within 1- and 2-month follow-ups post-treatment, respectively. Further ...

2. researchgate.net researchgate.net/publication/385753624_Efficacy_and_safety_of_transcranial_direct_current_stimulation_tDCS_in_treatment_of_refractory_epilepsy_an_updated_systematic_review_and_meta-analysis_of_randomized_sham-controlled_trials

Efficacy and safety of transcranial direct current stimulation ... This study aims to provide a comprehensive investigation of the efficacy and safety of tDCS in patients with drug-resistant epilepsy.

3. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03907-6

TRANscranial direct current stimulation for FOcal Refractory ... This study aims to evaluate whether tDCS can serve as an effective adjunctive treatment to reduce focal epilepsy in people with mitochondrial ...

4. springermedicine.com springermedicine.com/epilepsy/efficacy-and-safety-of-transcranial-direct-current-stimulation-t/50203364

Epilepsy | Efficacy and safety of transcranial direct current ... The IEDs were observed to significantly decline at 2, 4, and 8 weeks of follow-up. The reported adverse events were mild including mild itching ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11772517/

Efficacy and safety of transcranial direct current stimulation ... This study aims to provide a comprehensive investigation of the efficacy and safety of tDCS in patients with drug-resistant epilepsy.

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

Safety of transcranial Direct Current Stimulation: Evidence ... This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, ...

7. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1462364/full

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