Transcranial Electrical Stimulation for Bipolar Disorder

Overseen By Paulo Lizano, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Substance abuse, Pregnancy, Head injury, others

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

Compensation: Varies

Number of Visits: 10

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for people with bipolar disorder, specifically targeting symptoms of mania like feeling overly excited or taking big risks. The treatments use transcranial electrical stimulation, which applies small electrical currents to specific brain areas that might influence these symptoms. Participants will receive one of several types of stimulation, such as High-Definition Personalized Beta-Gamma Electrical Stimulation, to determine which works best. This trial may suit individuals who have experienced mania and are currently dealing with mild to moderate symptoms. As an unphased trial, it offers a unique opportunity to explore innovative treatments for managing mania symptoms.

Will I have to stop taking my current medications?

The trial requires that you do not change your mood stabilizing medications for at least 2 weeks before participating. So, you can continue taking your current medications as long as they are stable.

What prior data suggests that this technique is safe for treating bipolar disorder?

Previous studies have shown that both transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are safe for humans. Research indicates these treatments do not cause serious side effects, such as brain injury. Some common side effects, like skin irritation, have been reported but are usually mild and temporary.

For tDCS, studies found it to be a safe and well-tolerated option, even for individuals with conditions like bipolar disorder. Similarly, tACS has not been linked to any serious side effects. It is a non-invasive method that gently influences brain activity. While tDCS and tACS might sound complex, they simply apply small electrical currents to the scalp to aid brain function.

Overall, both treatments have been tested in humans and are considered safe, with no serious safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bipolar disorder because they utilize high-definition transcranial electrical stimulation techniques, which are different from traditional medication or psychotherapy approaches. Unlike typical treatments that primarily target chemical imbalances with drugs like lithium or valproate, these methods involve non-invasive electrical stimulation of the brain, offering a new way to potentially regulate mood. The personalized beta-gamma transcranial alternate-current stimulation (tACS) and high-definition transcranial direct-current stimulation (tDCS) target specific brain regions with precise electrical currents, which could lead to more rapid and tailored effects. This approach might offer an alternative for those who do not respond well to medications or who experience significant side effects. Researchers hope these innovative methods could provide faster and more personalized relief for individuals with bipolar disorder.

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

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS), a potential treatment in this trial, may improve mood and symptoms in individuals with bipolar depression. Studies have found that it can significantly enhance mood and increase activity in brain areas related to mood control.

Similarly, personalized beta-gamma transcranial alternating current stimulation (tACS) is another treatment option in this trial. Research suggests that tACS can improve mood and cognitive abilities in people with mood disorders like depression. Both treatments target brain areas that control mood and behavior, potentially helping to manage symptoms of bipolar disorder. ^{6 7 8 9 10}

Who Is on the Research Team?

Paulo Lizano, MD,PhD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with bipolar disorder or schizoaffective disorder, who have experienced mania before and are currently having mild to moderate symptoms. Participants must not have changed their mood stabilizers recently, should not be pregnant or breastfeeding, free from substance abuse in the last six months, and without a history of severe head injury or seizures.

Inclusion Criteria

I have been diagnosed with bipolar disorder or schizoaffective disorder, bipolar type.

Has not recently participated in tES/TMS treatments

Proficient in English

Exclusion Criteria

I have had a head injury with more than 15 minutes of unconsciousness.

I have had seizures in the past.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial electrical stimulation targeting the OFC for 5 days, with two 20-minute sessions per day

1 week

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including YMRS, ASRM, and other secondary measures

3 months

Long-term follow-up

Participants' psychiatric hospitalization rates for mania are compared from average per year prior to study entry to 1 year post study completion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• High-Definition Personalized Beta-Gamma Electrical Stimulation
• High-Definition Transcranial Alternate-Current Stimulation
• High-Definition Transcranial Electrical-Current Stimulation

Trial Overview Researchers are testing three types of non-invasive brain stimulation: High-Definition Transcranial Electrical-Current Stimulation (HD-tES), Alternate-Current Stimulation (HD-tACS), and Personalized Beta-Gamma Electrical Stimulation. These aim to target specific brain areas linked to mania symptoms like euphoria and risk-taking behaviors.

How Is the Trial Designed?

Group I: HD-tDCS Active Control 1 Intervention

HD-tDCS; Two, twenty-minute sessions of tDCS to the OFC for 5 days (10 total sessions)

Group II: HD-tACS (alpha, 10 Hz) Active Control 1 Intervention

10 Hz HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions).

Group III: Personalized Beta-Gamma HD-tACS Active Control 1 Intervention

Personalized HD-tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions).

High-Definition Personalized Beta-Gamma Electrical Stimulation is already approved in United States for the following indications:

Approved in United States as High-Definition Transcranial Direct Current Stimulation (tDCS) for:

• Investigational for bipolar mania
• Investigational for depression and anhedonia in bipolar disorder

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Published Research Related to This Trial

Transcranial direct current stimulation (tDCS) applied to the prefrontal and cerebellar regions significantly improved neuropsychological functioning in 25 euthymic patients with bipolar disorder over a 3-week period.

Patients demonstrated notable enhancements in visuospatial memory and executive functioning, particularly those with initially poorer cognitive performance, suggesting that tDCS may effectively modulate disrupted brain circuits in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder. Minichino, A., Bersani, FS., Bernabei, L., et al.[2020]

A high-resolution multi-layer skin model was developed to better predict current flow during transcranial electrical stimulation (tES), revealing that current concentration remains annular around electrode edges despite realistic tissue parameters.

The model demonstrated that adding structures like sweat glands and blood vessels can help distribute current more evenly, which aligns with experimental observations of skin reactions, such as erythema, during tES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of skin tissue layers and ultra-structure in transcutaneous electrical stimulation including tDCS. Khadka, N., Bikson, M.[2022]

High-definition transcranial direct current stimulation (HD-tDCS) is feasible and acceptable for patients with chronic post-stroke aphasia, showing that it can be implemented effectively in a clinical setting with similar protocols to conventional sponge-based tDCS.

Preliminary results indicate that HD-tDCS may improve naming accuracy and response time in patients, with some evidence suggesting it could be more effective than conventional tDCS, although the differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. Richardson, J., Datta, A., Dmochowski, J., et al.[2023]

A case study of a 33-year-old woman with bipolar II disorder revealed that transcranial direct current stimulation (tDCS) using a frontoextracephalic configuration induced hypomania, while a previous tDCS treatment with a bifrontal montage did not cause such symptoms.

This suggests that while frontoextracephalic tDCS may have antidepressant effects, it could also pose risks for inducing hypomanic symptoms in bipolar patients, indicating a need for caution and further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS). Gálvez, V., Alonzo, A., Martin, D., et al.[2011]

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 electrical stimulation (TES) can modulate brain activity using low-intensity currents, but the effects observed may not solely be due to the targeted brain region, as peripheral stimulation could also play a significant role.

The review emphasizes the need for careful consideration of TES's biophysical properties and dose-response relationships, suggesting that researchers should control for peripheral effects and be cautious in attributing behavioral changes to specific brain areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? Karabanov, AN., Saturnino, GB., Thielscher, A., et al.[2023]

In a study involving 70 healthy males, high-definition transcranial direct current stimulation (HD-tDCS) significantly increased resting-state functional connectivity (rsFC) between the right inferior frontal gyrus and the left prefrontal cortex compared to a sham group, indicating its potential therapeutic effects.

The study found considerable variability in the electric fields induced by HD-tDCS, suggesting that individualized head models are necessary to optimize treatment effects and minimize differences in patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HD-tDCS induced changes in resting-state functional connectivity: Insights from EF modeling. Müller, D., Habel, U., Brodkin, ES., et al.[2023]

Transcranial direct current stimulation (tDCS) is a promising non-invasive technique that can help relieve symptoms of psychiatric disorders, with evidence showing it induces plastic changes in the brain as detected by EEG and event-related potentials (ERPs).

A systematic review of 21 studies indicates that EEG and ERPs are effective markers for monitoring brain changes and symptom improvement after tDCS, although future research should standardize protocols to enhance the reliability of findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review. Kim, M., Kwak, YB., Lee, TY., 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]

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]

The novel high-definition transcranial direct current stimulation (HD-tDCS) setup was found to be safe and well-tolerated, with fewer adverse effects compared to conventional tDCS, based on a study involving 60 healthy participants.

HD-tDCS significantly improved cognitive performance on a visual task, indicating its potential for more effective neural modulation, while also being compatible with simultaneous fMRI without causing significant heating or image quality issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. Gbadeyan, O., Steinhauser, M., McMahon, K., et al.[2022]

Transcranial direct current stimulation (tDCS) appears to be well tolerated and safe for children and adolescents with various psychiatric disorders, based on a review of six studies, including three randomized clinical trials.

However, due to the limited number of studies and the need for more rigorous research, definitive conclusions about its efficacy compared to standard treatments cannot yet be made.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry. Muszkat, D., Polanczyk, GV., Dias, TG., et al.[2018]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

Citations

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Effect of high-definition transcranial direct current ... Active tDCS significantly alleviated depression symptoms. Additionally, active tDCS significantly increased ReHo values in the orbitofrontal cortex and middle ...

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Effect of home-based transcranial direct current stimulation ... A course of home-based tDCS in bipolar depression was associated with an improvement in verbal learning, which appeared to be related to improvement in ...

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Transcranial alternating current stimulation (tACS): from basic ... tACS is a unique form of non-invasive brain stimulation. Sinusoidal alternating electric currents are delivered to the scalp to affect mostly cortical neurons.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10403094/

Using gamma-band transcranial alternating current ... This is a randomized, double-blind, sham-controlled clinical trial comparing 40 Hz tACS with tDCS in mild neurocognitive disorders due to AD with sleep ...

8. withpower.com withpower.com/trial/phase-schizoaffective-disorders-6-2022-1deed

Transcranial Electrical Stimulation for Bipolar Disorder Research suggests that high-definition transcranial direct current stimulation (HD-tDCS) can modulate brain activity and improve symptoms in psychiatric ...

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Enhancing Neural Synchrony and Affective Cognitive Control in ... Bipolar Disorder using Personalized Transcranial Alternating. Current Stimulation (tACS). Study Design. The randomized, double-blind, sham-controlled, cross ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1364661322002984

Neurocognitive, physiological, and biophysical effects of ... Transcranial alternating current stimulation (tACS) is a non-invasive method for brain stimulation. It is the application of alternating currents to the ...