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

• ClinicalTrials.gov Identifier: NCT05772702
• Recruitment Status: Recruiting
• First Posted: March 16, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Electromedical Products International, Inc.
• Collaborator: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): Electromedical Products International, Inc.

Tracking Information

• First Submitted Date: February 24, 2023
• First Posted Date: March 16, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: February 13, 2023
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2024)

HDRS-17 change [ Time Frame: 19 days ]

Change in HDRS-17 between two week follow-up (FU2) and Day 1 (D1); minimum value is 0, maximum value is 52. Higher scores indicate worse outcome.

Original Primary Outcome Measures (submitted: March 6, 2023)

HDRS-17 change [ Time Frame: 21 days ]

Change in HDRS-17 between two week follow-up (FU2) and Day 1 (D1); minimum value is 0, maximum value is 52. Higher scores indicate worse outcome.

Current Secondary Outcome Measures (submitted: May 9, 2024)

• HDRS-17 change [ Time Frame: 5 days ]
  Change in HDRS-17 between D5 and D1
• Response/Remission of depression [ Time Frame: 19 days ]
  Number of response/remission rates at D5 and FU2
• Change in Quick Inventory of Depressive Symptomatology (QIDS) [ Time Frame: 19 days ]
  Change in QIDS at D5, FU1, FU2; minimum value is 0, maximum value is 27. Higher scores indicate worse outcome.
• Change in Altman Self-Rating Mania Scale (ASRM) [ Time Frame: 19 days ]
  Change in ASRM at D5, FU1, FU2; minimum value is 0, maximum value is 20. Higher scores indicate worse outcome.
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: 19 days ]
  Change in SHAPS at D5, FU1, FU2; minimum value is 0, maximum value is 14. Higher scores indicate worse outcome.
• Change in Depression Anxiety and Stress Scale (DASS-42) [ Time Frame: 19 days ]
  Change in DASS-42 at D5, FU1, FU2; minimum value is 0, maximum value is 126 with three subscales (0 to 42). Higher scores indicate worse outcome.
• Change in State-Train Anxiety Inventory (STAI) [ Time Frame: 19 days ]
  Change in STAI at D5, FU1, FU2; minimum value is 20, maximum value is 80. Higher scores indicate worse outcome.
• Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short form (Q-LES-Q-SF) [ Time Frame: 19 days ]
  Change in Q-LES-Q-SF at D5, FU1, FU2; minimum value is 14, maximum value is 70. Higher scores indicate better outcome.
• Change in Clinical Global Impression Scale (CGI) [ Time Frame: 19 days ]
  Change in CGI at Day 5, and 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.

Original Secondary Outcome Measures (submitted: March 6, 2023)

• HDRS-17 change [ Time Frame: 14 days ]
  Change in HDRS-17 between one week follow-up (FU1) and D1
• HDRS-17 change [ Time Frame: 5 days ]
  Change in HDRS-17 between D5 and D1
• Response/Remission of depression [ Time Frame: 21 days ]
  Number of response/remission rates at D5, FU1 and FU2
• Change in Quick Inventory of Depressive Symptomatology (QIDS) [ Time Frame: 21 days ]
  Change in QIDS at D5, FU1, FU2; minimum value is 0, maximum value is 27. Higher scores indicate worse outcome.
• Change in Altman Self-Rating Mania Scale (ASRM) [ Time Frame: 21 days ]
  Change in ASRM at D5, FU1, FU2; minimum value is 0, maximum value is 20. Higher scores indicate worse outcome.
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: 21 days ]
  Change in SHAPS at D5, FU1, FU2; minimum value is 0, maximum value is 14. Higher scores indicate worse outcome.
• Change in Depression Anxiety and Stress Scale (DASS-42) [ Time Frame: 21 days ]
  Change in DASS-42 at D5, FU1, FU2; minimum value is 0, maximum value is 126 with three subscales (0 to 42). Higher scores indicate worse outcome.
• Change in State-Train Anxiety Inventory (STAI) [ Time Frame: 21 days ]
  Change in STAI at D5, FU1, FU2; minimum value is 20, maximum value is 80. Higher scores indicate worse outcome.
• Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short form (Q-LES-Q-SF) [ Time Frame: 21 days ]
  Change in Q-LES-Q-SF at D5, FU1, FU2; minimum value is 14, maximum value is 70. Higher scores indicate better outcome.
• Change in Clinical Global Impression Scale (CGI) [ Time Frame: 21 days ]
  Change in CGI at Day 5, FU1 and 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.

Current Other Pre-specified Outcome Measures (submitted: May 13, 2024)

• Change in Alpha Oscillation Power [ Time Frame: 19 days ]
  Change in EEG alpha oscillation power at D1 pre-stimulation, D1 post-stimulation, and FU2.
• Change in Quick Inventory of Depressive Symptomatology (QIDS) Over 12 Weeks [ Time Frame: 89 days ]
  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.
• Change in Altman Self-Rating Mania Scale (ASRM) Over 12 Weeks [ Time Frame: 89 days ]
  Change in ASRM at FU3, FU4, FU5, FU6, and FU7; minimum value is 0, maximum value is 20. Higher scores indicate worse outcome.
• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Over 12 Weeks [ Time Frame: 89 days ]
  Change in SHAPS at FU3, FU4, FU5, FU6, and FU7; minimum value is 0, maximum value is 14. Higher scores indicate worse outcome.
• Change in Depression Anxiety and Stress Scale (DASS-42) Over 12 Weeks [ Time Frame: 89 days ]
  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.
• Change in State-Train Anxiety Inventory (STAI) Over 12 Weeks [ Time Frame: 89 days ]
  Change in STAI at FU3, FU4, FU5, FU6, and FU7; minimum value is 20, maximum value is 80. Higher scores indicate worse outcome.
• Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short form (Q-LES-Q-SF) [ Time Frame: 89 days ]
  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.
• HDRS-17 change [ Time Frame: 47 Days ]
  Change in HDRS-17 between six week follow up (FU4) and D1

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Depression
• Official Title: Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Depression (CLACS): Single-Site Open-Label Pilot Study
• Brief Summary: 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.

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
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open-Label

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Depression
• Major Depressive Disorder
• tACS

Intervention

Device: Closed-loop tACS

Individual alpha tACS

Study Arms

Experimental: Closed-loop tACS

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

Intervention: Device: Closed-loop tACS

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 16, 2024): 35
• Original Estimated Enrollment (submitted: March 6, 2023): 20
• Estimated Study Completion Date: August 15, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tobias U Schwippel, MD; 817-609-4460; tobias_schwippel@unc.edu

Contact: Zachary J Stewart; zachary_stewart@med.unc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05772702
• Other Study ID Numbers: 22-3094
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Electromedical Products International, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Electromedical Products International, Inc.
• Original Study Sponsor: Same as current
• Collaborators: University of North Carolina, Chapel Hill

Investigators

• Principal Investigator: David R Rubinow, MD; University of North Carolina, Chapel Hill

• PRS Account: Electromedical Products International, Inc.
• Verification Date: May 2024