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

NCT ID: NCT06003309

Last Updated: 2024-03-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-31

Study Completion Date

2025-04-01

Brief Summary

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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.

Detailed Description

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Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches)

In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.

Group Type ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS

Intervention Type DEVICE

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.

iTBS individualized using E-field targeting only (targeted-iTBS)

In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting.

Group Type ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation (TMS) - targeted-iTBS

Intervention Type DEVICE

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.

Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method)

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.

Group Type ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation (TMS) - Standard-iTBS

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Zafiris Daskalakis

Chair of Psychiatry Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of California, San Diego

La Jolla, California, United States

Site Status RECRUITING

Australian National University

Canberra, , Australia

Site Status RECRUITING

Countries

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United States Australia

Central Contacts

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Interventional Psychiatry

Role: CONTACT

858-207-0938

Facility Contacts

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Jessica Rico

Role: primary

858-966-5832

Bianca Bacio

Role: backup

858-657-6152

Shona Brinley

Role: primary

Other Identifiers

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807836

Identifier Type: -

Identifier Source: org_study_id

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