Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Depression (CLACS)

Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Depression (CLACS): Single-Site Open-Label Pilot Study

The purpose of this research study is to study closed-loop transcranial alternating current stimulation (tACS) to determine its effects on symptoms of depression in people with major depressive disorder.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder; tACS
• Intervention / Treatment: Device: Closed-loop tACS

Detailed Description

The purpose of this clinical trial is to investigate the preliminary efficacy of closed-loop tACS for the treatment of major depressive disorder (MDD) in an open-label pilot study. We will recruit up to 35 participants with unipolar, non-psychotic MDD. Participation will include seven visits, two of them remotely (with an in-person option as needed), and one electronic survey.

Potential participants fill-in an electronic pre-screening form. If potentially eligible, a remote screening visit is performed. If eligible, participants attend five consecutive, daily stimulation sessions. Clinical assessments will be performed at baseline (Day 1 of stimulation, D1), Day five of stimulation (D5), and at their follow-up visit (14 days after the completion of stimulation, FU2) using the Hamilton Depression Rating Scale (HDRS-17).

For a subset of patients, electroencephalography (EEG) is collected at D1 prior to stimulation and after stimulation and again at FU2.

For a subset of patients, self-scoring surveys will be sent bi-weekly until 12 weeks after treatment.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Carolina Center for Neurostimulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 18-70 years
• Diagnostic and Statistical Manual, 5th Edition (DSM-5) diagnosis of MDD; unipolar, non-psychotic
• Hamilton Rating Depression Rating Scale (HRDS-17) score >8
• Low suicide risk as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) triage form (no intent or plan)
• Capacity to understand all relevant risks and potential benefits of the study (informed consent)

Exclusion Criteria:

• DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months.
• DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months.
• Lifetime history of bipolar disorder, psychotic disorder, schizophrenia, autism
• Current use of benzodiazepines > 20mg diazepam/d equivalent
• Antidepressant dose change within the last 2 weeks
• Initiated new antidepressant within the last 4 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Closed-loop tACS; Closed-loop individual alpha tACS daily for five consecutive days.	Device: Closed-loop tACS; Individual alpha tACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Depression Rating Scale 17-item (HDRS-17)	Change in HDRS-17 from Day 1 (D1) to Day 19 (i.e., two week follow-up; FU2); HDRS-17 minimum value is 0, maximum value is 52. Higher scores indicate worse outcome. Negative scores indicate improved outcomes.	Day 1 to Day 19 (i.e. 19 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Depression Rating Scale 17-item (HDRS-17)	Change in HDRS-17 from Day 1 (D1) to Day 5 (D5); HDRS-17minimum value is 0, maximum value is 52. Higher scores indicate worse outcome. Negative scores indicate improved outcomes.	Day 1 to Day 5 (i.e., 5 days)
Response/Remission of Depression	Number of response/remission rates at Day 5 (D5) and Day 19 (i.e., two week follow-up; FU2). Response defined as >=50% reduction in HDRS-17 from D1. Remission defined as HDRS-17 score <=7.	Day 5 and Day 19
Change in Quick Inventory of Depressive Symptomatology (QIDS)	Change in QIDS at Day 5 (D5), Day 12 (i.e., one-week follow-up; FU1), and Day 19 (i.e., two-week follow-up; FU2); QIDS minimum value is 0, maximum value is 27. Higher scores indicate worse outcome. Negative scores indicate improved outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in Altman Self-Rating Mania Scale (ASRM)	Change in ASRM at Day 5 (D5), Day 12 (i.e., one week follow-up; FU1), and Day 19 (i.e., two week follow-up; FU2); ASRM minimum value is 0, maximum value is 20. Higher scores indicate worse outcome. Negative scores indicate improved outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in Snaith-Hamilton Pleasure Scale (SHAPS)	Change in SHAPS from Day 1 (D1) to Day 5 (D5), Day 12 (i.e., one week follow-up; FU1), and Day 19 (i.e., two week follow-up; FU2); SHAPS minimum value is 0, maximum value is 14. Higher scores indicate worse outcome. Negative scores indicate improved outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in Depression Anxiety and Stress Scale (DASS-42)	Change in DASS-42 from Day 1 (D1) to Day 5 (D5), Day 12 (i.e., one week follow-up; FU1), and Day 19 (i.e., two week follow-up; FU2); DASS-42 minimum value is 0, maximum value is 126 with three subscales (0 to 42). Higher scores indicate worse outcome. Negative scores indicate improved outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in State-Train Anxiety Inventory (STAI)	Change in STAI from Day 1 (D1) to Day 5 (D5), Day 12 (one week follow-up; FU1), and Day 19 (two week follow-up; FU2); STAI minimum value is 20, maximum value is 80. Higher scores indicate worse outcome. Negative scores indicate improved outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF)	Change in Q-LES-Q-SF from Day 1 (D1) to Day 5 (D5), Day 12 (i.e., one week follow-up; FU1), and Day 19 (i.e., two week follow-up; FU2); Q-LES-Q-SF minimum value is 14, maximum value is 70. Higher scores indicate better outcome. Negative scores indicate worse outcome.	Day 1 (D1) to Day 5 (D5); D1 to Day 12 (FU1); and D1 to Day 19 (FU2)
Change in Clinical Global Impression Scale (CGI)	Change in CGI from Day 1 (D1) to Day 5 (D5) and Day 19 (i.e., two week follow-up; FU2); CGI scale contains two scoring components, 1) Severity of Illness (0-7) and 2) Global Improvement (0-7). Higher scores in component 1 indicate worse symptoms while higher numbers in component 2 indicate worse clinical outcomes.	Severity: {Day 1 (D1), Day 5 (D5) and Day 19 (FU2)}; Global Improvement: {Day 5 (D5) and Day 19 (FU2)}

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alpha Oscillation Power	Change in EEG alpha oscillation power at D1 pre-stimulation, D1 post-stimulation, and FU2.	19 days
Change in Quick Inventory of Depressive Symptomatology (QIDS) Over 12 Weeks	Change in QIDS at four week follow-up (FU3), six week follow-up (FU4), eight week follow-up (FU5), ten week follow-up (FU6), and twelve week follow-up (FU7); minimum value is 0, maximum value is 27. Higher scores indicate worse outcome.	89 days
Change in Altman Self-Rating Mania Scale (ASRM) Over 12 Weeks	Change in ASRM at FU3, FU4, FU5, FU6, and FU7; minimum value is 0, maximum value is 20. Higher scores indicate worse outcome.	89 days
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Over 12 Weeks	Change in SHAPS at FU3, FU4, FU5, FU6, and FU7; minimum value is 0, maximum value is 14. Higher scores indicate worse outcome.	89 days
Change in Depression Anxiety and Stress Scale (DASS-42) Over 12 Weeks	Change in DASS-42 at FU3, FU4, FU5, FU6, and FU7; minimum value is 0, maximum value is 126 with three subscales (0 to 42). Higher scores indicate worse outcome.	89 days
Change in State-Train Anxiety Inventory (STAI) Over 12 Weeks	Change in STAI at FU3, FU4, FU5, FU6, and FU7; minimum value is 20, maximum value is 80. Higher scores indicate worse outcome.	89 days
Change in Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF)	Change in Q-LES-Q-SF at FU3, FU4, FU5, FU6, and FU7; minimum value is 14, maximum value is 70. Higher scores indicate better outcome.	89 days
HDRS-17 Change	Change in HDRS-17 between six week follow up (FU4) and D1	47 Days

Collaborators and Investigators

• Sponsor: Electromedical Products International, Inc.
• Collaborators: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: David R Rubinow, MD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Alexander ML, Alagapan S, Lugo CE, Mellin JM, Lustenberger C, Rubinow DR, Frohlich F. Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD). Transl Psychiatry. 2019 Mar 5;9(1):106. doi: 10.1038/s41398-019-0439-0.

Helpful Links

• Link to more information and study recruitment for interested potential participants.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Actual): April 22, 2024
• Study Completion (Actual): August 19, 2024

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 22-3094

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