Brief, High-dose rTMS for Depression

Not Applicable

Recruiting

• Conditions: Anxiety; Depression
• Interventions: Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

• Registration Number: NCT04657432
• Lead Sponsor: Medical University of South Carolina

Brief Summary

High frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to be safe, feasible, and acceptable. Conventionally, rTMS investigations have relied on rational decision trees for dosage determination. The purpose of this study is to systematically examine an accelerated protocol of intermittent theta burst (iTBS). Study 1 aims to provide a quantifiable dose-response curve for iTBS and depressive symptom reduction in major depression. Study 2 aims to determine the role of individual variations of their functional networks compared to the site of stimulation and clinical outcomes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2020-12-01
• Study First Posted: 2020-12-08
• Study Start: 2021-05-25
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2025-06-30
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• A negative urine pregnancy test, if female subject of childbearing potential.
• Able to speak English and complete study forms, adhere to treatment regimens, and be willing to return for regular visits.
• After full explanation of the study, willingness of participant is demonstrated by signing the informed consent form.

Exclusion Criteria

• Clinically unstable medical disease:

  • cardiovascular
  • renal
  • gastrointestinal
  • pulmonary
  • metabolic
  • endocrine
  • other

• CNS disease deemed progressive

• Moderate or severe traumatic brain injury (TBI)

• Pregnant females or those currently breast-feeding.

• Current or history of schizophrenia or other psychotic disorder, except psychosis not otherwise specified (NOS) when the presence of sensory hallucinations is clearly related to the subject's trauma, Bipolar Type I disorder, or dementia:

  • vascular
  • Alzheimer's disease
  • other types

• Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) within 6 days of study entry, with the exception of alcohol use disorder, which, at the discretion of the study team, may be permitted.

See further explanation under protection from risk.

• Active participation or plan for enrollment in another evidence-based psychotherapeutic clinical trial

• Participation in other psychotherapeutic modalities must have been stable for 3 months prior to enrollment and must remain stable throughout participation.

• Currently taking medications that have short half-lives, lower the seizure threshold, and do not have evidence of antidepressant efficacy. These include:

  • high dose theophylline or stimulants such as methylphenidate patients taking bupropion must be on a stable dose and take less than or equal to 300 mg/day. Stable means the same dose for 5 half-lives.

• An implanted device in subject's head (shunt, cochlear implant) and/or metal in subject's head (other than dental implant).

• History of seizures or a seizure disorder.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose 2	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 2 is 10 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 5	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 5 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 6	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 6 is 25 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 4	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 4 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 7	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 7 is 30 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 1	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 9	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 9 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Study 2: 10 Active Doses	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be assigned to 10 sessions (per treatment day) of accelerated rTMS for 5 treatment days. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 50 active sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 3	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 3 is 15 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 8	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 8 is 35 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.
Dose 10	Repetitive Transcranial Magnetic Stimulation (rTMS)	All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

Primary Outcome Measures

Name	Time	Method
Depression severity (change in score)	Day 1, post-treatment point of 1 month	Depression severity as assessed by: 3. Beck Depression Inventory-II (BDI-II) Rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

Secondary Outcome Measures

Name	Time	Method
Comorbid symptom severity, functional impairment, acceptability, and tolerability	Day 1, post-treatment point of 1 month	Participants would complete various questionnaires (change in score assessed): 12. Quality of Life and Enjoyment and Satisfaction Questionnaire -Short Form (Q-LES-Q-SF); -Questions are rated on a 5 point scale (from 1-5) Likert scale. The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70.

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States