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

Major Depressive Disorder Clinical Trial

— FREED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06003309
• Other study ID #: 807836
• Status: Recruiting
• Phase: N/A
• Start date: August 31, 2023
• Est. completion date: April 1, 2025

Study information

• Verified date: February 2024
• Source: University of California, San Diego
• Contact: Interventional Psychiatry
• Phone: 858-207-0938
• Email: iptrials[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder disorder.

• 18-80 years of age.

• Male or female.

• At least one failed antidepressant medication trial at level 3 in the Antidepressant Treatment History Form: Short Form (ATHF-SF) classification.

• Montgomery-Asberg Depression Rating Scale (MADRS) Score of >19 (moderate - severe depression).

• No increase or initiation of new antidepressant therapy in the four weeks prior to screening.

• Demonstrated capacity to give informed consent.

Exclusion Criteria:

• Inability to provide informed consent.

• Medically unstable patients.

• Concomitant neurological disorder or a history of a seizure disorder.

• Patients who are pregnant or breastfeeding.

• Any psychotic disorder or current active psychotic symptoms.

• Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS.

• Contraindication to MRI scanning.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Australian National University	Canberra
United States	University of California, San Diego	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from pre-treatment in fronto-parietal theta connectivity at post-treatment	Source-localized fronto-parietal theta connectivity will be calculated from resting EEG	pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)