Recruiting

cTBS & iTBS

Sponsor:

Mclean Hospital

Code:

NCT07758010

Conditions

Depressive Disorder, Treatment-Resistant

Treatment Resistant Depression (TRD)

Treatment Resistant Major Depression Disorder

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Precuneus-targeted continuous theta-burst stimulation

Left dorsolateral prefrontal cortex intermittent theta-burst stimulation

Sham transcranial magnetic stimulation

Study Details

Brief summary:

The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain.

The main questions this study aims to answer are:

  • Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?
  • Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation?

Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive.

Participants will:

  • Complete screening procedures and baseline assessments of depression, rumination, and cognitive function
  • Receive 20 sessions of active or sham TMS during one in-person study day
  • Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention
  • Report any side effects or medical problems experienced during the study

Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.

Conditions

Depressive Disorder, Treatment-Resistant

Treatment Resistant Depression (TRD)

Treatment Resistant Major Depression Disorder

Study ID

NCT07758010

Start date

Sep 8, 2026

Status verified date

Sep, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 18 years or older.
  • Able to speak, read, and understand English sufficiently to complete the study assessments and provide informed consent independently.
  • Diagnosis of major depressive disorder according to DSM-5-TR criteria, confirmed by a qualified physician.
  • Treatment-resistant depression, defined as an inadequate response to at least two adequate trials of antidepressant pharmacotherapy.
  • Patient Health Questionnaire-9 (PHQ-9) total score of 10 or higher.

Exclusion Criteria:

  • Any condition identified through TMS safety screening that, in the judgment of a study physician, presents an unacceptable safety risk for TMS. Such conditions may include:
  • A history of a serious adverse reaction during TMS treatment.
  • A history of seizure.
  • A history of stroke.
  • A history of serious head injury or neurosurgery.
  • Metal in the head outside the mouth, such as shrapnel, surgical clips, or metal fragments.
  • An implanted device, such as a cardiac pacemaker, cochlear implant, medical pump, or intracardiac line.
  • Frequent or severe headaches.
  • Another brain-related condition or an illness that caused brain injury.
  • A family history of epilepsy.
  • Permanent tattoos on the head or neck.
  • Current recreational drug use.
  • Current pregnancy or possible pregnancy.
  • Use of a medication or combination of medications, a recent medication change, or medication withdrawal that, in the judgment of a study physician, presents an unacceptable safety risk, including a clinically significant increase in seizure risk.
  • Current or lifetime diagnosis of bipolar I disorder, bipolar II disorder, a schizophrenia spectrum disorder, or another primary psychotic disorder.
  • Active suicidal ideation with intent or plan requiring immediate clinical intervention, or another acute safety concern that cannot be safely managed within the study.

Study Design

Enrollment

69 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Precuneus cTBS

Participants receive 20 sessions of active continuous theta-burst stimulation (cTBS) targeting the Pz location of the international 10-20 EEG system during a single day. Stimulation is delivered using a double-cone coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 40 seconds, for a total of 12,000 pulses. Session onsets are separated by approximately 30 minutes. If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

experimental: Left dlPFC iTBS

Participants receive 20 sessions of active intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex during a single day. The target is identified using the Beam F3 method, and stimulation is delivered using a figure-of-eight coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 3 minutes, for a total of 12,000 pulses. Session onsets are separated by approximately 30 minutes. If stimulation at 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

sham comparator: Sham TMS

Participants receive 20 sessions of sham TMS at the left dorsolateral prefrontal cortex location identified using the Beam F3 method during a single day. A figure-of-eight coil is inverted so that the active surface faces away from the scalp. The device is operated at 80% of the participant's resting motor threshold, and sham stimulation follows the same stimulation pattern and approximate 3-minute duration as active iTBS. Session onsets are separated by approximately 30 minutes. After completing the Week 4 assessment, participants may enter an optional open-label extension and are randomized to receive active precuneus cTBS or left dlPFC iTBS.

Interventions

Precuneus-targeted continuous theta-burst stimulation

Active continuous theta-burst stimulation is delivered to the Pz location of the international 10-20 EEG system to target the precuneus. Stimulation is administered with a double-cone coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 40 seconds. Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes. If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

Left dorsolateral prefrontal cortex intermittent theta-burst stimulation

Active intermittent theta-burst stimulation is delivered to the left dorsolateral prefrontal cortex. The stimulation target is identified using the Beam F3 method. Stimulation is administered with a figure-of-eight coil at 80% of the participant's resting motor threshold. Each session consists of 600 pulses delivered over approximately 3 minutes. Participants receive 20 sessions during a single day, for a total of 12,000 pulses, with session onsets separated by approximately 30 minutes. If 80% of resting motor threshold is not tolerated, the intensity may be reduced to the highest tolerable level.

Sham transcranial magnetic stimulation

Sham transcranial magnetic stimulation is administered at the left dorsolateral prefrontal cortex location identified using the Beam F3 method. A figure-of-eight coil is inverted so that the active surface faces away from the scalp. The stimulator is operated at 80% of the participant's resting motor threshold using the same intermittent theta-burst timing and approximate session duration as the active left dorsolateral prefrontal cortex intervention. Participants receive 20 sham sessions during a single day, with session onsets separated by approximately 30 minutes.

Primary outcome measure

  • Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 4 [ Time Frame: Baseline and 1, 2, 3, and 4 weeks after the intervention ]

Central Contacts and Locations

Central contacts

Hakjoo Kim Kim, Ph.D.

979-777-0679khj213@gmail.com

Locations

McLean Hospital

Recruiting

Belmont, Massachusetts, United States, 02478

Contacts

Hakjoo Kim, PhD

617-855-4203hkim128@mclean.harvard.edu

Principal Investigator:

Hakjoo Kim, PhD

More Information

Sponsor

Mclean Hospital

Last update posted

Sep 11, 2026

Last verified

Sep, 2026

Keywords

  • Treatment-resistant depression
  • Accelerated transcranial magnetic stimulation
  • Precuneus
  • Dorsolateral prefrontal cortex
  • Continuous theta burst stimulation
  • Intermittent theta burst stimulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-12. This information was provided to ClinicalTrials.gov by Mclean Hospital on 2026-09-11.