Accelerated Versus Standard Intermittent Theta Burst Stimulation for Major Depressive Disorder

NCT07768397 | Not Yet Recruiting

• 1 other identifier: KCB-TT.15-MDD
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized clinical trial aims to compare the effectiveness and safety of accelerated intermittent theta burst stimulation (iTBS) with standard iTBS in adults with major depressive disorder. Participants will be randomly assigned to receive either accelerated or standard iTBS targeting the left dorsolateral prefrontal cortex, in addition to pharmacotherapy. The accelerated iTBS group will receive 45 treatment sessions over approximately 15 treatment days, while the standard iTBS group will receive 20 treatment sessions over 4 weeks. The primary objective is to compare changes in depressive symptom severity between the two treatment groups from baseline to the end of treatment. Depressive symptoms will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17). The study will also evaluate other clinical outcomes, cognitive function, quality of life, sleep quality, neurophysiological measures, and treatment safety.

Conditions

Major Depressive Disorder

Keywords

Intermittent Theta Burst Stimulation; iTBS; Transcranial Magnetic Stimulation; Accelerated iTBS; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in 17-Item Hamilton Depression Rating Scale (HAM-D17) Score From Baseline to End of Treatment

  Depressive symptom severity will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17). The total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. The primary outcome is the change in HAM-D17 total score from baseline (T0) to the end-of-treatment assessment (T4).

  Baseline (T0) and 24-72 hours after the final treatment session (T4)

Secondary Outcomes (7)

• Treatment Response Based on HAM-D17

  From baseline (T0) to end of treatment (T4), assessed 24-72 hours after the final treatment session

• Remission Based on HAM-D17

  End of treatment (T4), assessed 24-72 hours after the final treatment session

• Change in Sleep Quality Assessed by the Pittsburgh Sleep Quality Index (PSQI)

  From baseline (T0) to end of treatment (T4), assessed 24-72 hours after the final treatment session

• Change in Quality of Life Assessed by the WHOQOL-BREF

  From baseline (T0) to end of treatment (T4), assessed 24-72 hours after the final treatment session

• Change in Cognitive Function Assessed by the Montreal Cognitive Assessment (MoCA)

  From baseline (T0) to end of treatment (T4), assessed 24-72 hours after the final treatment session

Other Outcomes (2)

• Change in Individual Alpha Frequency (IAF)

  Baseline (T0) and 24-72 hours after the final treatment session (T4)

• Changes in TMS-EEG Measures

  Baseline (T0) and 24-72 hours after the final treatment session (T4)

Study Arms (2)

Accelerated iTBS

EXPERIMENTAL

Participants receive accelerated intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex in addition to background pharmacotherapy. Treatment is administered at 100% of the resting motor threshold, with 1,200 pulses per session. Participants receive three sessions per treatment day, separated by 30-minute intervals, over 15 consecutive weekdays, for a total of 45 sessions.

Device: Accelerated Intermittent Theta Burst Stimulation

Standard iTBS

ACTIVE COMPARATOR

Participants receive standard intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex in addition to background pharmacotherapy. Treatment is administered at 120% of the resting motor threshold, with 600 pulses per session, one session per weekday, 5 days per week for 4 weeks, for a total of 20 sessions.

Device: Standard Intermittent Theta Burst Stimulation

Interventions

Accelerated Intermittent Theta Burst Stimulation DEVICE

Intermittent theta burst stimulation (iTBS) is delivered to the left dorsolateral prefrontal cortex using the Beam F3 approach. Stimulation consists of triplet bursts at 50 Hz repeated at 5 Hz, with 2 seconds on and 8 seconds off. Each session consists of 1,200 pulses delivered at 100% of the resting motor threshold. Participants receive three sessions per day, separated by 30-minute intervals, over 15 consecutive weekdays, for a total of 45 sessions.

Accelerated iTBS

Standard Intermittent Theta Burst Stimulation DEVICE

Intermittent theta burst stimulation (iTBS) is delivered to the left dorsolateral prefrontal cortex. Stimulation consists of triplet bursts at 50 Hz repeated at 5 Hz, with 2 seconds on and 8 seconds off. Each session consists of 600 pulses delivered at 120% of the resting motor threshold, with a duration of approximately 3 minutes. Participants receive one session per weekday, 5 days per week for 4 weeks, for a total of 20 sessions.

Standard iTBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years.
• Diagnosis of major depressive disorder (MDD), confirmed by a specialist according to DSM-5 criteria.
• Hamilton Depression Rating Scale, 17-item version (HAM-D17) score ≥18 at screening/baseline.
• Stable background pharmacotherapy for at least 4 weeks before randomization, with no planned changes in medication regimen or drug class during the intervention period unless clinically required.
• Right-handed.
• Able and willing to provide written informed consent and comply with study procedures.

You may not qualify if:

• History of epilepsy or seizures, except childhood febrile seizures.
• Bipolar disorder or psychotic disorder.
• Acute suicide risk, including HAM-D17 item 3 score ≥3 or clear suicidal intent or behavior.
• Alcohol or illicit drug abuse or dependence within the previous 6 months.
• Significant structural brain lesions.
• Intracranial or head/neck metallic objects or implants considered unsafe for TMS, including metallic clips, fragments, or cochlear implants.
• Implanted electronic devices such as pacemakers, implantable cardioverter-defibrillators, or deep brain stimulation devices.
• Other conditions associated with a high risk of seizure or history of cranial surgery considered unsafe for TMS.
• Uncontrolled thyroid dysfunction.
• Severe untreated vitamin D deficiency (\<20 ng/mL).
• Acute infection, elevated C-reactive protein, or other clinically significant medical abnormalities that may interfere with study participation.
• Pregnancy or breastfeeding.
• Benzodiazepine use exceeding the equivalent of lorazepam 2 mg/day that cannot be reduced.
• Use of medications associated with a substantially lowered seizure threshold, including clozapine, high-dose tricyclic antidepressants, or bupropion \>300 mg/day.
• Unstable doses of antiepileptic medications used as mood stabilizers.

Sponsors & Collaborators

• Military Hospital 175: lead

Study Sites (1)

Military Hospital 175

Ho Chi Minh City, 700000, Vietnam

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Dang Minh Ly, MD

CONTACT

+84359999741; drminhdang@outlook.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors will be blinded to treatment allocation. Participants and personnel administering the intervention will not be blinded because of differences in the treatment schedules. Participants will be instructed not to disclose their treatment allocation to outcome assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department of Neurology

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 17, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 17, 2026

Record last verified: 2026-08

Locations

VN (1)