Recruiting

iTBS, Psychotherapy, tACS

Sponsor:

University of North Carolina, Chapel Hill

Code:

NCT07507370

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Intermittent Theta Burst Stimulation (iTBS)

Transcranial Alternating Current Stimulation (tACS)

Psychotherapy

Sham (Placebo) Transcranial Alternating Current Stimulation (tACS)

Study Details

Brief summary:

The purpose of this study is to primarily assess the feasibility and secondarily assess the efficacy of a single session intervention (SSI) that combines non-invasive brain stimulation and psychotherapy for Major Depressive Disorder (MDD). investigators will recruit 30 people with MDD, with at least mild to moderate symptoms, who are resistant to typical treatments for Major Depressive Disorder. In this trial, participants will receive psychotherapy, Intermittent Theta Burst Stimulation Transcranial Magnetic Stimulation (iTBS), and either active or sham (placebo) Transcranial Alternating Current Stimulation (tACS).

Conditions

Major Depressive Disorder

Study ID

NCT07507370

Start date

Apr 14, 2026

Status verified date

Mar, 2026

Completion date

Jul 1, 2028

Anticipated

Primary completion date

Jul 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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 Diagnostic Interview for Anxiety, Mood, and Obsessive-Compulsive and Related Neuropsychiatric Disorders (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 Columbia-Suicide Severity Rating Scale (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
  • History of treatment resistance as indicated by previously or currently not achieving clinically significant symptom reduction on at least one antidepressant medication. This will be evaluated using the Maudsley Treatment Inventory (MTI). Participants with scores greater than or equal to 3 on the MTI will be included.

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 (self-reported by participants)
  • 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
  • Personal or familia history of epilepsy
  • Previous fainting spells or syncope
  • Metal in the brain, skull or elsewhere in the body
  • Implanted medical device that uses electricity and any implanted devices in other areas of the head or neck, or implants located < 30cm from the position of the TMS coil
  • Current pregnancy or lactation
  • Currently enrolled in another clinical trial for depression
  • 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
  • Non-English speaking individuals are excluded because the ability to accurately and completely communicate study information, answer questions about the study, and obtain consent in the English language are necessary, and due to resource constraints it is not feasible to engage an interpreter for language services.

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Inactive Sham (Placebo)

Participants will receive psychotherapy, active iTBS, and sham tACS in which alpha-theta tACS is delivered for 40 seconds before ramping down to close to 0 mA of current. The sham is designed to mimic the sensation of receiving Alpha and Theta tACS without delivering a sufficient dose.

experimental: Active tACS: Experimental Arm

Participants will receive psychotherapy, active iTBS, and active tACS in which alpha-theta tACS will be delivered with a 20 second ramp up and ramp down, at the beginning and end of stimulation followed by 2 mA between the stimulation sites. The stimulation amplitude delivered is standard for tACS studies conducted in the Frohlich Lab

Interventions

Intermittent Theta Burst Stimulation (iTBS)

The TMS stimulation will be delivered using the MagPro X100 system (MagVenture Inc., Alpharetta, Georgia, USA). Participants will receive theta-burst stimulation (iTBS) consisting of 1,800 biphasic pulses delivered in bursts of three pulses at 50 Hz, repeated at 5 Hz (2-s trains, 8-s inter-train interval, 30 trains total per block), at an intensity of 90 % of the resting motor threshold. TMS will be delivered before each tACS/therapy block (over the tACS electrodes), totaling 5 blocks of TMS throughout the single session intervention.

Transcranial Alternating Current Stimulation (tACS)

The alpha and -theta tACS stimulation will be delivered using the neuroConn DC Stimulator MC.The interventional tACS stimulation will be 120 minutes of tACS total; 60 minutes will be delivered during the second block of therapy and 60 minutes will be delivered during the third block of therapy.F3 and F4 will be stimulated 'in-phase', with 1 mA applied at each location, and Cz will be stimulated 'anti-phase' with 2mA applied (zero to peak). tACS will be delivered with a 20 second ramp up and ramp down, at the beginning and end of stimulation. The stimulation amplitude delivered is standard for tACS studies conducted in the Frohlich Lab.

Psychotherapy

The three, 1-hour psychotherapy blocks were designed to incorporate effective components from multiple psychotherapies, with an emphasis on functional analysis to define the presenting concern, followed by Behavioral Activation (BA) and Acceptance and Commitment Therapy modules to target low mood and psychological flexibility, respectively.

The SSI was designed to incorporate ACT principles throughout the modules, guided by the tenets of psychological flexibility, as described by Hayes. Be present, open up, do what matters. The manual was created by a team of several advanced clinical trainees and two licensed clinical psychologists. The last 10 minutes of each session will be spent briefly reviewing the day's activities, what stood out for participants (negative or positive), and whether they had feedback for the clinician.

Sham (Placebo) Transcranial Alternating Current Stimulation (tACS)

Participants will be fitted with the same tACS setup and will receive sham tACS in which alpha-theta tACS is delivered for 40 seconds before ramping down to close to 0 mA of current (20 second ramp up and ramp down; total 80 seconds of stimulation). This active sham is designed to mimic the sensation of receiving stimulation without delivering a sufficient dose of tACS to influence the efficacy of the SSI.

Primary outcome measure

  • Safety via the presence of any serious AEs [ Time Frame: Day 0 (Baseline) to Day 90 (Follow-up 2) ]
  • Feasibility of the Single Session Intervention [ Time Frame: Day 0 (Baseline) ]

Central Contacts and Locations

Central contacts

Flavio Frohlich, PhD

919-966-9929flavio_frohlich@med.unc.edu

Haileigh Taylor, BA

919-966-9929hjtay@unc.edu

Locations

Carolina Center for Neurostimulation

Recruiting

Chapel Hill, North Carolina, United States, 27516

Contacts

Flavio Frohlich, PhD

919-966-9929flavio_frohlich@med.unc.edu

More Information

Sponsor

University of North Carolina, Chapel Hill

Last update posted

Jun 25, 2026

Last verified

Mar, 2026

Keywords

  • Non-invasive Brain Stimulation
  • Psychotherapy
  • Transcranial Magnetic Stimulation
  • Single Session Intervention
  • tACS
  • Behavioral Activation
  • Depression
  • Transcranial Alternating Current Stimulation
  • Acceptance and Commitment Therapy
  • Mood Disorders
  • Brief Intervention
  • TMS
  • Neurostimulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of North Carolina, Chapel Hill on 2026-06-25.