Clinical trial NCT06874374: Individualized Non-invasive Brain Stimulation for the Treatment of Major Depressive Disorder
Official title: Closed-Loop Transcranial Alternating Current Stimulation (CL-tACS) for the Treatment of Major Depressive Disorder: Double-Blind, Sham-Controlled Randomized Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depression - Major Depressive Disorder
Transcranial Alternating Current Stimulation
Keywords: tACS
Depression
Major Depressive Disorder
Transcranial Alternating Current Stimulation
Lead sponsor: Pulvinar Neuro, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Mental Health (NIMH)
name: University of North Carolina, Chapel Hill
First posted: 2025-03-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.

Detailed description: The purpose of this study is to investigate device feasibility and performance of the XCSITE 100 Pro V2 device and assess preliminary efficacy of closed-loop transcranial alternating current stimulation (CL-tACS) for reducing symptoms of major depressive disorder (MDD) in a double-blind, sham-controlled, parallel group, single-site clinical trial. A total of 40 participants will be randomized to receive active or sham CL-tACS via carbon-silicone electrodes for up to 40 minutes over 5 consecutive days. Device feasibility and performance data will be collected from every stimulation session. Clinical assessments of depression and related symptoms will be performed at Baseline (Day 1), End Of Treatment (EOT; Day 5), and Follow-Up (FUP, 2-weeks post-treatment, Day 19). High-density electroencephalography (HD-EEG) will be performed at Baseline, EOT and FUP. An optional MRI will be performed up to 30 days before, or on Baseline, to provide anatomical data for EEG brain connectivity analysis.

Eligibility criteria: Inclusion Criteria:

* Any gender, aged 18 - 70
* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* DSM-5 diagnosis of unipolar, non-psychotic MDD as evidenced by the DIAMOND
* HDRS-17 score ≥14
* Low suicide risk (defined for this study as no active suicidal ideation in the past month and no suicide attempts, preparatory actions, or significant non-suicidal self-harm in the previous 2 years). Risk will be assessed utilizing the C-SSRS screen and triage version with further exploration of positive responses.
* Capacity to understand all relevant risks and potential benefits of the study (informed consent)
* 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:

* DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND
* DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months, as evidenced by the DIAMOND
* Lifetime history of bipolar disorder, as evidenced by DIAMOND
* Schizophrenia spectrum and other psychotic disorders, as evidenced by DIAMOND
* History of autism spectrum disorder
* Initiated any new psychotropic medication in the 6 weeks prior to screening or had a dose change in the preceding 6 weeks
* Initiated a new course of psychotherapy in the 6 weeks preceding screening
* Received any neurostimulation treatment in the 6 weeks preceding screening
* History of seizures (excluding febrile seizures in childhood or Electroconvulsive Therapy (ECT) induced seizures)
* Neurological disorders that would increase risk of participation or present a significant confounder in the opinion of the investigator (for example, dementia, history of stroke, Parkinson's disease, multiple sclerosis, history of traumatic brain injury with prolonged loss of consciousness, ruptured cerebral aneurysm, previous CNS radiation)
* Previously failed to respond to ECT or transcranial magnetic stimulation (TMS)
* Prior brain surgery and/or brain implants
* Implanted medical device that uses electricity
* Current pregnancy or lactation
* Currently enrolled in another clinical trial for depression
* For the optional MRI session only: Contraindication to MRI according to MRI Screening Form
* Unstable medical disorder or anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the opinion of the Investigator

Primary outcomes:
measure: Correct Assignment by Device of Study Arm
timeFrame: 5 days
measure: Accuracy of Device Study Arm Parameters by Device
timeFrame: 5 days
measure: Accuracy of Stimulation Initiation Based on EEG by Device
timeFrame: 5 days
measure: Accuracy of Device Logs Uploaded to Cloud by Device
timeFrame: 5 days
Secondary outcomes:
measure: HDRS-17 Change
timeFrame: 21 Days
measure: Change in Alpha Oscillation Power
timeFrame: 5 Days
Other outcomes:
measure: Change in Alpha Oscillation Power and Connectivity
timeFrame: 21 Days
measure: Remission Rate
timeFrame: 21 Days
measure: Response Rate
timeFrame: 21 Days
measure: SSRI Effect on HDRS-17 Change
timeFrame: 21 Days
measure: Change in Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: 21 Days
measure: Change in Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: 21 Days
measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short form (Q-LES-Q-SF)
timeFrame: 21 Days
measure: Change in Clinical Global Impression Scale (CGI)
timeFrame: 21 Days
Locations:
city: Chapel Hill
country: United States
facility: Carolina Center for Neurostimulation
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: David Rubinow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwippel T, Pupillo F, Feldman Z, Walker C, Townsend L, Rubinow D, Frohlich F. Closed-Loop Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder: An Open-Label Pilot Study. Am J Psychiatry. 2024 Sep 1;181(9):842-845. doi: 10.1176/appi.ajp.20230838. Epub 2024 Aug 7. No abstract available.
citation: 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.