Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder

August 20, 2026 updated by: Pulvinar Neuro, LLC

Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder: Double-Blind, Controlled Randomized Multicenter Clinical Trial

The purpose of this research study is to investigate a closed-loop transcranial alternating current stimulation (tACS) device to evaluate its ability to reduce symptoms of major depressive disorder

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study examines the efficacy of closed-loop transcranial alternating current stimulation (CL-tACS) for the treatment of major depressive disorder (MDD) in a double-blind, controlled parallel group multi-site clinical trial. 214 participants will be randomized into receiving 5 consecutive days of active or control CL-tACS (1:1 allocation) to achieve approximately 192 participants completing the primary endpoint at week 3, assuming a 10% lost to follow-up rate. Clinical assessments of depression and anxiety symptoms are performed at Screening, Baseline, Day 5, Follow-Up 1 (week 3), and Follow-Up 2 (week 5). Additional assessments of quality of life are included.

For subjects who are not considered responders at the Week 3 primary endpoint, there will be a phase 2 retreatment with active CL-tACS which will mirror the same 5-day protocol. Patients in this arm will complete additional data collection at Phase 2 baseline, Phase 2 Day 5, Phase 2 Follow-up 1 (phase 2 week 3), and phase 2 follow-up 2 (phase 2 week 5).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
214

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27707
        • Qortical Clinical Partners
        • Contact:
        • Principal Investigator:
          • David Rubinow, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. ≥ 22 years of age;
  2. with at least moderate symptom severity (HAM-D17 ≥ 17);
  3. who are currently in a depressive episode;
  4. who have used at least 1 antidepressant in the current or previous episode, but have not found adequate symptom relief or who were not able to tolerate medication side effects;

  5. who, for 6 weeks prior to enrollment, are either;

    • not taking antidepressant medication, or:
    • are taking a stable psychiatric medication regimen with one or more stable antidepressant medication dose(s) and agree to continue the same regimen throughout study participation
  6. if currently engaged in depression-focused psychotherapy, have maintained stable frequency of therapy for at least 8 weeks prior to enrollment and agree to continue the same regimen throughout study participation;
  7. are able and willing to comply with the protocol and follow up schedule and protocol, in the opinion of the investigator;
  8. who understand English and are able to provide written informed consent;
  9. who are currently under the care of a psychiatric clinician or a primary care physician for major depressive disorder, and who agree to promptly inform the study staff of any change of psychiatric or mental health providers during study participation;
  10. who agree to allow any and all forms of communication between the investigators/study staff and their current or past (within 2 years) healthcare providers;
  11. who agree to provide the names and verifiable contact information (email and mailing addresses, mobile and/or land-line phone numbers, as applicable) for at least two persons (≥ age 18) who reside within a 60-minute drive of their residence and whom the research staff are at liberty to contact, as they deem necessary, to ensure participant safety for the duration of study participation;

Exclusion Criteria:

  1. Subjects with current / past six months use of an external stimulation device for MDD, including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain or cranial nerve stimulation;
  2. Subjects with (lifetime) history of failure to response to an adequate trial of ECT, TMS, or implanted vagus nerve stimulation;
  3. Subjects who currently receive esketamine, ketamine, or psilocybin treatment
  4. Subjects who are pregnant or of childbearing potential and not using adequate contraception, as determined by the investigator;
  5. Subjects who are breastfeeding.
  6. Subjects whose current depressive episode had onset within 6 months post-partum;
  7. Presence of active skin disorder on the forehead that could be exacerbated by stimulation electrodes in the opinion of the investigator.
  8. Subjects with clinical or historical features which, in the opinion of the investigator, make them an inappropriate candidate for participation in this trial;
  9. Subjects whose current depressive episode has not responded to 3 or more adequate trials of FDA approved antidepressant medications;
  10. Subjects with current suicidal ideation with plan or intent, or suicidal behavior or preparation in the past 3 months, as determined by CSSRS assessment or by the Investigator;
  11. Subjects with a diagnosis of epilepsy or unexplained seizures;
  12. Subjects with a diagnosis or clinical history suggestive of bipolar disorder, hypomania, mania, or psychosis, as determined by the Investigator and/or by the DIAMOND assessment.
  13. Subjects currently participating, or intending to participate (during the next 3 months) in another study involving an investigational drug or device treatment that, in the opinion of the investigator, could impact symptoms of MDD or use of the investigational device;
  14. Subjects with a history of intracranial surgery;
  15. Subjects with implanted neurostimulators, nonremovable or implanted electrical devices or intracranial metal objects, with the exception of dental metal;
  16. Subjects with cognitive impairment or memory disorders, which, in the opinion of the investigator, could impact their ability to comply with study requirements;
  17. Subjects currently meeting diagnostic criteria for obsessive compulsive disorder determined by the Investigator and/or by the DIAMOND assessment;
  18. Subjects who meet DSM-V criteria for moderate/severe alcohol use disorder or other substance use disorders (except tobacco/nicotine) within the past 6 months as confirmed by the DIAMOND interview;
  19. Subjects who meet DSM-V criteria for moderate/severe cannabis use disorder (CUD) within the past 6 months as confirmed by the DIAMOND interview. Subjects with recreational or prescription use (including medical marijuana cards) not considered moderate to severe CUD will be included.
  20. Subjects with a current neurological condition or disease which, in the opinion of the investigator, is likely to manifest a depressive syndrome or symptoms that would substantially confound the diagnosis or serial assessment of major depressive disorder.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active Closed-loop tACS
Closed-loop individual alpha tACS daily for five consecutive days.
Device: Closed-loop tACS
Individual alpha tACS
Sham Comparator: Sham Closed-loop tACS
Sham closed-loop individual alpha tACS daily for five consecutive days.
Device: Sham Comparator
Sham stimulation
Experimental: Open Label, Active Closed-loop tACS Retreatment
An open label, second dose of Closed-loop individual alpha tACS daily for five consecutive days. Assignment to this arm occurs after participation in the closed label active or sham arms.
Device: Closed-loop tACS
Individual alpha tACS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response rates (at least 50% reduction in Hamilton Depression Rating Scale (HDRS) score) at Week 3 Phase 1 Evaluation
Time Frame: Timeframe: Baseline to Week 3
Response rates (at least 50% reduction in HDRS-D17 score) (0-52 score range, higher score is worse) in Active vs. Control groups.
Timeframe: Baseline to Week 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in mean Hamilton Depression Rating Scale (HDRS) Score
Time Frame: Timeframe: Baseline to Week 3
Change in mean HDRS-17 Score (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Week 3
The State-Trait Anxiety Inventory (STAI) Score
Time Frame: Timeframe: Baseline to week 3, Phase 1
Change in self-reported anxiety symptoms STAI Trait (score range is 20-80, higher is worse) in Active vs Control groups
Timeframe: Baseline to week 3, Phase 1
Hamilton Depression Rating Scale (HDRS) Remission Rate
Time Frame: Timeframe: Baseline to Week 3, Phase 1
Remission rates (HDRS-17 score ≤ 7) (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Week 3, Phase 1
Difference in change in Hamilton Depression Rating Scale (HDRS) in Active vs control groups between patients with MDD and GAD and patients with MDD and not GAD
Time Frame: Timeframe: Baseline to Week 3
Difference in the change in mean HDRS-17 Score (0-52 score range, higher score is worse) in Active vs Control groups between MDD patients with and without a comorbid GAD diagnosis.
Timeframe: Baseline to Week 3
Hamilton Depression Rating Scale (HDRS) Remission Rate at Day 5
Time Frame: Timeframe: Baseline to Day 5
Remission rates (HDRS-17 score ≤ 7) (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Day 5
Response rates (at least 50% reduction in Hamilton Depression Rating Scale (HDRS) score) at Day 5
Time Frame: Timeframe: Baseline to Day 5
Responder rates (at least 50% reduction in HDRS-17 score) (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Day 5
Change in Hamilton Depression Rating Scale (HDRS) Score at Day 5
Time Frame: Timeframe: Baseline to Day 5
Change in HDRS-17 Score (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Day 5
Difference in change in Hamilton Depression Rating Scale (HDRS) in Active vs control groups between patients with MDD and GAD and patients with MDD and not GAD at Day 5
Time Frame: Timeframe: Baseline to Day 5
Difference in the change in mean HDRS-17 Score (0-52 score range, higher score is worse) in Active vs Control groups between MDD patients with and without a comorbid GAD diagnosis.
Timeframe: Baseline to Day 5
Remission rates (Hamilton Depression Rating Scale (HDRS) score ≤ 7) at Week 5
Time Frame: Timeframe: Baseline to Week 5
Remission rates (HDRS-17 score ≤ 7) (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Week 5
Response rates (at least 50% reduction in Hamilton Depression Rating Scale (HDRS) score) at Week 5
Time Frame: [Timeframe: Baseline to Week 5].
Responder rates (at least 50% reduction in HDRS-17 score) (0-52 score range, higher score is worse) in Active vs Control groups.
[Timeframe: Baseline to Week 5].
Change in Hamilton Depression Rating Scale (HDRS) score at Week 5
Time Frame: Timeframe: Baseline to Week 5
Change in HDRS-17 (0-52 score range, higher score is worse) in Active vs Control groups.
Timeframe: Baseline to Week 5
Difference in change in Hamilton Depression Rating Scale (HDRS) in Active vs control groups between patients with MDD and GAD and patients with MDD and not GAD at Week 5
Time Frame: Timeframe: Baseline to Week 5
Difference in the change in mean HDRS-17 Score (0-52 score range, higher score is worse) in Active vs Control groups between MDD patients with and without a comorbid GAD diagnosis.
Timeframe: Baseline to Week 5

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hamilton Depression Rating Scale (HDRS) Score reduction, at study end
Time Frame: At the phase 1, week 3 assessment OR at the phase 2, week 3 assessment.
Response rates (at least 50% reduction in HDRS-17 score) for patients at their study completion. This will be evaluated by determining the percentage of patients from the active stimulation arm who can be classified as responders either at the phase 1, week 3 assessment OR at the phase 2, week 3 assessment. (0-52 score range, higher score is worse)
At the phase 1, week 3 assessment OR at the phase 2, week 3 assessment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pulvinar Neuro, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark George, MD, Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 5, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 15, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PN1000

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings