NCT06003309

Frequency and E-field Enhancement of ITBS for Depression (FREED)

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The investigators propose a randomized 3-arm double-blinded parallel experimental trial (20 sessions over 4 weeks) in 75 patients with TRD. The three arms include (1) the combination of a fully Individualized form of intermittent Theta Burst Stimulation (iTBS) (using BOTH the frequency and electric field (E-field) targeting approaches) (Ind-iTBS)), (2) iTBS individualized using E-field targeting only (targeted-iTBS) and (3) Standard iTBS treatment (i.e., typical iTBS localized to the dorsolateral prefrontal cortex (DLPFC) using the Beam F3 method). Electroencephalography (EEG) data will be collected at rest and during a working memory task, at baseline, and at the end of treatment along with clinical assessments of depression severity. The target engagement dependent variable of interest in these three arms will be fronto-parietal theta connectivity measured through resting-state EEG. The investigators hypothesize that stimulation with Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity than that produced with targeted-TBS and standard iTBS. Aim: To evaluate the effects of two individualized forms of iTBS (i.e., using BOTH the frequency and E-field individualization; Ind-iTBS) compared to iTBS individualized for E-field targeting only (targeted-iTBS) and standard iTBS on fronto-parietal theta connectivity. Hypotheses: (1) Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity compared to both targeted-iTBS and standard iTBS. (2) Ind-iTBS will also lead to a greater reduction in depressive symptoms (as defined by the mean reduction in Montgomery Åsberg Depression Rating Scale Scores (MADRS)) compared to both targeted-iTBS and standard iTBS.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DEVICE	Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS	Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.
DEVICE	Transcranial Magnetic Stimulation (TMS) - targeted-iTBS	Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting.
DEVICE	Transcranial Magnetic Stimulation (TMS) - Standard-iTBS	Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. The standard iTBS will be delivered with the typical 5Hz/50Hz patterned frequencies used in the FDA approved treatment protocol and stimulation will be delivered according to the Beam F3 targeting.

Timeline

• Start date: 2023-08-31
• Primary completion: 2025-12-30
• Completion: 2025-12-30
• First posted: 2023-08-21
• Last updated: 2026-02-13

Locations

2 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated device study