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

Trial Summary

What is the purpose of this trial?

The purpose of this research is to see to what extent electrical stimulation applied to the scalp (transcranial direct current stimulation or tDCS) can reduce the number and intensity of epileptic seizures.

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 data supports the effectiveness of this treatment for epilepsy?

Research shows that transcranial direct current stimulation (tDCS) is a safe, non-invasive method that has been tried in drug-resistant epilepsies, like mesial temporal lobe epilepsy, although results on its effectiveness are mixed. In animal studies, tDCS has been shown to decrease convulsions and improve memory after seizures. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with no serious adverse effects reported in over 33,200 sessions. Mild side effects like itching, tingling, and headaches are common but usually temporary. Safety has been established for low-intensity tDCS, defined as less than 4 milliamperes for up to 60 minutes per day. ^{6 7 8 9 10}

How does the treatment ActivaDose II tDCS for epilepsy differ from other treatments?

ActivaDose II tDCS is a unique, non-invasive brain stimulation treatment that uses weak direct currents to modulate brain activity, potentially reducing seizures by altering cortical excitability. Unlike traditional drug treatments, it is pain-free and can be tailored in terms of intensity and duration to achieve lasting effects. ^{1 3 11 12 13}

Research Team

Brian Lundstrom, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats. [2022]

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

Transcranial Direct Current Stimulation in Epilepsy. [2018]

3. Netherlands 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. [2019]

4. Ireland 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. [2021]

5. United States 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. [2023]

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

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

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

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Modulation of cortical excitability by transcranial direct current stimulation]. [2019]

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

Anticonvulsant effects of transcranial direct-current stimulation (tDCS) in the rat cortical ramp model of focal epilepsy. [2022]

13. United States 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. [2022]