An interventional study of Intermittent Theta Burst Stimulation (iTBS) and Transcranial Alternating Current Stimulation (tACS) in Major Depressive Disorder, sponsored by University of North Carolina, Chapel Hill. Recruiting at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by University of North Carolina, Chapel Hill · Not applicable, Interventional, and Treatment
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).
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 interventions for Major Depressive Disorder. In this trial, participants will receive 3 interventions in a single session: psychotherapy, Intermittent Theta Burst Stimulation (iTBS), and participants will be randomized to receive either active or placebo Transcranial Alternating Current Stimulation (tACS). Additionally, Clinical assessments of depression symptoms are performed at Screening (for eligibility), Baseline (at start of day, prior to any intervention), Follow up 1 (FUP1); 2 weeks after SSI) and Follow up 2 (FUP2; 3 months after SSI). Additional assessments of anxiety symptoms, emotion regulation, clinical improvement and quality of life are included.
Primary Objective:
Second Objective:
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 30 is below the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,372 studies on the registry; 133 are open to participants now.
Of its 161 completed or terminated interventional studies of FDA-regulated products, 139 (86%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Device: Intermittent Theta Burst Stimulation (iTBS) · Behavioral: Psychotherapy · Device: Sham (Placebo) Transcranial Alternating Current Stimulation (tACS)
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
Device: Intermittent Theta Burst Stimulation (iTBS) · Device: Transcranial Alternating Current Stimulation (tACS) · Behavioral: Psychotherapy
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.
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.
Also known as: NeuroConn DC Stimulator MC, NeuroConn LOOP-IT
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.
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.
Safety via the presence of any serious AEs
The number of serious adverse events (SAEs) determined to be related to intervention in both experimental and sham arms.
Time frame: Day 0 (Baseline) to Day 90 (Follow-up 2)
Feasibility of the Single Session Intervention
Number of enrolled participants who successfully complete the intervention session.
Time frame: Day 0 (Baseline)
Change in Hamilton Depression Rating Scale-17 (HDRS-17) score following Single Session Intervention.
The HDRS-17 is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 52. A higher score indicates a worse outcome. Investigators will determine the change in scores across the intervention from Day 0 (Baseline) to Day 14 (Follow-up 1).
Time frame: Day 1 (Baseline) to Day 14 (Follow-up 1)
Duration of change in Hamilton Depression Rating Scale-17 (HDRS-17) score following Single Session Intervention.
The HDRS-17 is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 52. A higher score indicates a worse outcome. Investigators will determine the change in scores between Day 14 (Follow Up 1) to Day 90 (Follow-up 2) to establish the longevity of treatment effectiveness (if effective) via Follow Up timepoints overall and for both arms.
Time frame: Day 14 (Follow Up 1) to Day 90 (Follow-up 2)
Plan to share: No — Individual participant data will not be shared in this study due to the small sample size, which may cause participants to become identifiable
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