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?

This trial explores a new approach to assist individuals with major depressive disorder (MDD) using a brain stimulation device called closed-loop transcranial alternating current stimulation (tACS). The researchers aim to determine the device's safety and its potential effects on depression symptoms. Participants will receive either the active treatment or a sham (placebo-like) treatment for five days. Suitable candidates have non-psychotic MDD and experience symptoms that disrupt daily life. As an unphased trial, this study provides participants the chance to contribute to groundbreaking research that could lead to new treatment options for MDD.

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.

What prior data suggests that this closed-loop tACS device is safe for treating depression?

Research has shown that closed-loop transcranial alternating current stimulation (tACS) is generally safe for people with depression. In one study, after 5 days of tACS treatment, 80% of participants experienced symptom improvement or resolution.

Other studies also demonstrate that tACS can effectively reduce depression symptoms. Reports indicate that the treatment is well-tolerated, with participants not experiencing major side effects.

Overall, evidence suggests that tACS is a safe option for treating depression, with most people handling it well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, which often involve medications like SSRIs or cognitive behavioral therapy, closed-loop tACS is unique because it uses a non-invasive brain stimulation technique. This treatment specifically targets the brain's alpha waves and adjusts stimulation in real-time based on the brain's activity, aiming to enhance its effectiveness. Researchers are excited about this approach because it offers a personalized treatment experience that could potentially lead to quicker and more significant improvements in mood without the side effects associated with traditional antidepressants.

What evidence suggests that this closed-loop tACS device is effective for depression?

Research has shown that closed-loop transcranial alternating current stimulation (tACS) may aid in treating major depressive disorder (MDD). In one study, 80% of participants experienced improvement or complete relief from symptoms just two weeks after a 5-day treatment with closed-loop tACS. Another study found that tACS reduced depression symptoms when used at specific settings. This trial will compare the effects of active closed-loop tACS with a sham version to evaluate its effectiveness. These findings suggest that closed-loop tACS could offer a non-invasive option for improving symptoms in people with depression. ^{1 2 5 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

For people of childbearing potential: use of highly effective contraception as determined by the Investigator for at least 1 month prior to screening and agreement to use such a method during study participation

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

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]

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]

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) 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12177679/

Transcranial Electrical Stimulation in Treatment of Depression Among tES modalities, tDCS was associated with a significant improvement in depressive symptoms among patients with DMC (SMD = −1.05; 95% CI, − ...

2. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.20230838

Closed-Loop Transcranial Alternating Current Stimulation ... Overall, following the completion of a 5-day course of CL-tACS, we observed an 80% response rate and an 80% remission rate 2 weeks post- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001025

Effect of add-on transcranial alternating current stimulation ... A study examining tACS's role in treating MDD revealed that tACS with 15 mA and 77.5 Hz was effective in alleviating depressive symptoms in MDD [8]. However, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39108159/

Closed-Loop Transcranial Alternating Current Stimulation ... Closed-loop transcranial alternating current stimulation for the treatment of major depressive disorder: an open-label pilot study.

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20240603

“Closing the Loop” With Transcranial Electrical Stimulation ... The current findings provide preliminary evidence that “closing the loop” may improve tES antidepressant effects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11759093/

Transcranial Alternating Current Stimulation (tACS) for ... The outcome of this study suggests that tACS can reduce depressive symptoms in adults with MDD. Furthermore, this study demonstrates that tACS ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07185451

Efficacy and Safety of Transcranial Alternating Current ... To assess adverse events and side effects in both the intervention and control groups, ensuring the safety and tolerability of tACS in adolescent populations.