Brain Stimulation for Depression

(CL-tACS RCT Trial)

Overseen By Zachary Stewart

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Pulvinar Neuro, LLC

Must not be taking: Psychotropics, Neurostimulation

Disqualifiers: Severe AUD, Bipolar, Schizophrenia, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 week

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this research study is to study a closed-loop transcranial alternating current stimulation (tACS) device to evaluate feasibility of the product in a clinical trial and collect preliminary data on potential effects on symptoms of depression in people with major depressive disorder.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you should not have started any new psychotropic medications or changed doses in the 6 weeks before screening.

Is transcranial alternating current stimulation (tACS) safe for humans?

Research indicates that tACS is generally safe and well-tolerated in humans, with no severe adverse events reported in studies involving patients with major depressive disorder. Some participants experienced mild side effects like tinnitus (ringing in the ears), but these were not severe. ^{1 2 3 4 5}

How is the treatment Closed-loop tACS different from other treatments for depression?

Closed-loop tACS is a unique non-invasive brain stimulation method that uses alternating electric currents to influence brain activity by targeting specific brain oscillations. Unlike traditional treatments like medication, it aims to modulate brain function directly, potentially offering a new option for those who do not respond to drugs. ^{1 2 4 6 7}

What data supports the effectiveness of the treatment Closed-loop tACS for depression?

Research shows that transcranial alternating current stimulation (tACS) can help improve symptoms in people with major depressive disorder by altering brain activity patterns. Studies have found that tACS can reset disturbed brain oscillations, which may lead to better mood and behavior outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

David Rubinow, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for individuals with major depressive disorder who are interested in a non-invasive treatment option. Specific eligibility criteria details were not provided, so participants should inquire about inclusion and exclusion factors.

Inclusion Criteria

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

I understand the risks and benefits of the study.

Exclusion Criteria

I have not had any neurostimulation treatments in the last 6 weeks.

For the optional MRI session only: Contraindication to MRI according to MRI Screening Form

DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham closed-loop tACS for up to 40 minutes over 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Optional MRI

An optional MRI will be performed up to 30 days before, or on Baseline, to provide anatomical data for EEG brain connectivity analysis

What Are the Treatments Tested in This Trial?

Interventions

• Closed-loop tACS

Trial Overview The study tests a closed-loop transcranial alternating current stimulation (tACS) device against a sham comparator to see if it's feasible in trials and if it can improve depression symptoms.

How Is the Trial Designed?

Group I: Active Closed-loop tACS Experimental Treatment 1 Intervention

Closed-loop individual alpha tACS daily for five consecutive days.

Group II: Sham Closed-loop tACS Placebo Group 1 Intervention

Sham closed-loop individual alpha tACS daily for five consecutive days.

Who Is Running the Clinical Trial?

Pulvinar Neuro, LLC

Lead Sponsor

Trials

1

Recruited

40+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Published Research Related to This Trial

Transcranial alternating current stimulation (tACS) is a promising non-invasive brain stimulation technique that can reset disturbed brain oscillations, potentially improving behavioral outcomes in psychiatric disorders, with initial studies showing no serious adverse events.

The review highlights that tACS may serve not only as a therapeutic tool but also as a diagnostic aid for psychiatric conditions, suggesting its dual role in both treatment and understanding of mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. Elyamany, O., Leicht, G., Herrmann, CS., et al.[2023]

In a study involving 15 healthy adults, transcranial alternating current stimulation (tACS) at 5 Hz and 1 mA significantly improved working memory scores and increased brain activity in theta and delta frequency bands, indicating its potential to enhance cognitive function.

The study also established a closed-loop evaluation method that uses individual brain signals to optimize tACS protocols, suggesting that personalized stimulation durations can prevent overstimulation and improve effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness assessment of repetitive transcranial alternating current stimulation with concurrent EEG and fNIRS measurement. Yang, D., Ghafoor, U., Eggebrecht, AT., et al.[2023]

Transcranial alternating current stimulation (TACS) has demonstrated significant efficacy in improving symptoms of depression, with a standardized mean difference (SMD) of 1.14, indicating a strong positive effect compared to sham stimulation in patients.

TACS also showed a notable improvement in cognitive function among patients with psychiatric disorders, with an SMD of 0.60, suggesting it may enhance cognitive abilities in both patients and healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis. Lee, ARYB., Yau, CE., Mai, AS., et al.[2022]

Transcranial alternating current stimulation (tACS) showed a significant improvement in depressive symptoms for patients with major depressive disorder (MDD) compared to sham treatment, based on a meta-analysis of 4 randomized controlled trials involving 224 participants.

The treatment was found to be safe, with similar discontinuation rates between the active tACS and sham groups, indicating that tACS could be a viable option for managing MDD symptoms, although more research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis. Zheng, W., Cai, DB., Nie, S., et al.[2023]

Transcranial alternating current stimulation (tACS) is a promising non-invasive treatment for major depressive disorder (MDD), particularly for patients who do not respond to medications, as it manipulates brain oscillations to potentially alleviate symptoms.

Recent studies highlight two effective tACS techniques—high-definition tACS and bifocal tACS—that target specific brain areas and their connections, showing positive results in reducing MDD symptoms, although challenges remain in optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation for the treatment of major depressive disorder: from basic mechanisms toward clinical applications. Pan, R., Ye, S., Zhong, Y., et al.[2023]

The study evaluates the efficacy and safety of transcranial alternating current stimulation (tACS) in treating major depressive disorder (MDD) over 8 weeks, involving 92 drug-naive patients who received either active or sham stimulation.

The primary outcome is the remission rate measured by the Hamilton depression rating scale, with the study aiming to demonstrate that tACS can effectively reduce depression symptoms with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. Wang, HX., Wang, K., Zhang, WR., et al.[2023]

In a pilot study involving 30 drug-naive adults with major depressive disorder, transcranial alternating current stimulation (tACS) at 77.5 Hz and 15 mA showed a significant remission rate of 10 out of 15 patients at week 8, compared to only 3 out of 15 in the sham group.

The tACS treatment was well-tolerated with no severe adverse events reported, indicating it is a safe and acceptable intervention for treating depressive symptoms in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder]. Wang, HX., Wang, K., Sun, ZC., et al.[2020]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness assessment of repetitive transcranial alternating current stimulation with concurrent EEG and fNIRS measurement. [2023]

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

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial alternating current stimulation for the treatment of major depressive disorder: from basic mechanisms toward clinical applications. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder]. [2020]