Brain Stimulation for Epilepsy

Enrolling by invitation at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Stanford University

Must be taking: Anti-seizure medicines

Disqualifiers: Psychogenic seizures, Suicide attempt, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 month

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a device called transcranial direct current stimulation (tDCS), used at home, can reduce seizures and abnormal brain activity in people with epilepsy. Participants will undergo either a short daily session of tDCS for 1 minute or a longer session for 30 minutes, both over 30 days. Ideal participants are adults with epilepsy who experience at least four seizures a month and have not responded to at least two different anti-seizure medications. As an Early Phase 1 trial, this research aims to understand how this new treatment works in people, offering participants the opportunity to be among the first to try this innovative approach.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. You need to keep your medication the same during the study, but rescue medications are allowed.

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

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people with epilepsy. Studies have found that tDCS is well-tolerated, with most individuals experiencing no serious side effects. A meta-analysis, which combines results from several studies, found that tDCS not only helps reduce seizures but is also well-tolerated by patients.

Some individuals might experience mild side effects like tingling or itching on the scalp, but these effects are usually temporary and not harmful. Overall, the evidence suggests that tDCS is a safe option for managing epilepsy symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for epilepsy rely on medications that stabilize electrical activity in the brain, such as antiepileptic drugs. However, transcranial Direct Current Stimulation (tDCS) is unique because it uses a non-invasive method to deliver a gentle electrical current to the brain, potentially altering brain activity patterns without medication. Researchers are excited about tDCS because it offers a new approach to managing epilepsy symptoms, with one treatment arm involving just a short, 1-minute daily stimulation session and another offering a longer, 30-minute daily session. This flexibility in treatment duration could lead to more personalized and accessible epilepsy care, potentially reducing side effects associated with long-term medication use.

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

Research has shown that transcranial direct current stimulation (tDCS) can help reduce the number of seizures. In this trial, participants will receive either short stimulation (1 minute per day) or long stimulation (30 minutes per day) for 30 days. Studies have found that tDCS lowered seizures by about 28% after one month and 49% after two months. It also improves the unusual brain activity seen in epilepsy. People with medication-resistant epilepsy often benefit from tDCS, which usually has few side effects. Overall, tDCS offers a promising and non-invasive way to manage seizures. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 with epilepsy, experiencing at least four seizures per month and who haven't found seizure control with two or more anti-seizure medications. Participants must be able to keep their medication constant, understand consent in English, and maintain a seizure diary. It's not suitable for those with certain psychiatric conditions, skin issues affecting electrode placement, or women who are pregnant.

Inclusion Criteria

Age 18-100, inclusive.

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

Subject or legally authorized representative is able to understand consent and keep a seizure diary in English

Exclusion Criteria

You have non-epileptic seizures caused by psychological factors.

You have attempted suicide or been hospitalized for a mental health issue within the past 2 years.

Women will verify not pregnant, and if applicable, have a serum pregnancy test

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 month

1 visit (in-person)

Baseline

Participants maintain a seizure diary and undergo baseline EEG and neuropsychological testing

1 month

1 visit (in-person), weekly phone contacts

Treatment

Participants receive either SHORT or LONG tDCS treatment at home

1 month

1 visit (in-person), weekly phone contacts

Wash-out

No treatment is administered to allow for wash-out period

1 month

1 visit (in-person)

Second Treatment

Participants receive the alternate tDCS treatment (LONG or SHORT) at home

1 month

1 visit (in-person), weekly phone contacts

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person), weekly phone contacts

What Are the Treatments Tested in This Trial?

Interventions

• tDCS

Trial Overview The study tests if using transcranial direct current stimulation (tDCS) at home can reduce the number of seizures and EEG spikes in people with epilepsy. This placebo-controlled study means some participants will receive the tDCS treatment while others will get a sham procedure without any active intervention.

How Is the Trial Designed?

Group I: Long Stimulation Experimental Treatment 1 Intervention

30 minutes duration of stimulation per day for 30 days

Group II: Short Stimulation Active Control 1 Intervention

1 minute duration of stimulation per day for 30 days

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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) 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]

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]

Spaced transcranial direct current stimulation (tDCS) significantly reduced interictal epileptiform discharges (IEDs) by up to 68% and decreased seizure frequency in 15 adults with drug-resistant focal epilepsy, indicating its efficacy as a treatment option.

The treatment was well tolerated with no severe adverse events reported, suggesting that tDCS is a safe intervention for patients with unifocal epilepsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies. Kaufmann, E., Hordt, M., Lauseker, M., et al.[2021]

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) applied at 2 mA over the seizure focus in four patients with focal status epilepticus led to significant reductions in interictal spikes and electrographic seizures, demonstrating its potential efficacy in critical care settings.

The treatment was well-tolerated with only minor side effects, and it allowed for reductions in antiseizure medications, suggesting a promising role for tDCS in managing refractory seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting. Fisher, RS., McGinn, RJ., Von Stein, EL., et al.[2023]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

A systematic review of 158 studies involving 4130 participants found that repeated sessions of transcranial direct current stimulation (tDCS) do not significantly increase the risk of adverse events compared to sham treatments.

The study indicated that adverse event rates were consistent across different diagnostic groups, suggesting that tDCS is generally safe for various populations, although the potential for rare adverse events cannot be completely excluded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repeated sessions of transcranial direct current stimulation: A systematic review. Nikolin, S., Huggins, C., Martin, D., et al.[2019]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39588230/

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.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0920121124001712

A meta-analysis of RCTs and non-RCTs tDCS significantly reduced seizures at 4 weeks and 8 weeks , with improvements in epileptiform discharges. •. Mechanisms, influencing factors, and advances like ...

4. karger.com karger.com/ene/article/88/1/18/918769/Effectiveness-of-Transcranial-Direct-Current

Effectiveness of Transcranial Direct Current Stimulation in ... Conclusion: tDCS reduces seizure frequency in patients with drug-resistant focal epilepsy and is associated with minimal adverse effects.

5. academic.oup.com academic.oup.com/braincomms/article/7/1/fcaf012/8024004

Epileptogenic zone characteristics determine effectiveness of ... Transcranial direct current stimulation shows promise as a non-invasive therapeutic method for patients with focal drug-resistant epilepsy.

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

Efficacy and safety of transcranial direct current stimulation ... We found that tDCS significantly reduces IEDs and SF in patients with drug-resistant epilepsy. Active tDCS was more effective than sham tDCS in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0965229925000172

The safety and effectiveness of tDCS for epileptic patients The current evidence is limited to support tDCS treatment for depression, anxiety, and cognitive function in epilepsy patients.

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000206380

A Systematic Review and Meta-analysis (P3-1.011) Results: Eight RCTs were included with a total of 242 patients. Compared to the sham group, tDCS patients had a significantly lower seizure ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X19303699

Transcranial direct current stimulation reduces seizure ... Our study found active tDCS, compared with sham tDCS, produced a significant reduction in SFs in patients with refractory focal epilepsy. The protocol using 2 × ...