Theta-Burst Stimulation to Treat Depression

Summary

The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on brain plasticity and depression severity in depressed individuals aged 18 to 50 years old. Brain plasticity is the brain's ability to change through growth or reorganization. iTBS is a form of transcranial magnetic stimulation (TMS), where magnetic pulses are applied to the scalp using a coil. These pulses pass through the scalp, and can alter brain activity in the area underneath the coil. Based on previous research conducted in animals and humans, researchers believe that iTBS can strengthen the connections between cells in the brain, leading to improved brain plasticity.

This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced iTBS (iTBS-s) protocol. Researchers want to find out which protocol is better able to produce changes in brain plasticity and improve symptoms of depression among individuals diagnosed with Major Depressive Disorder (MDD). In this trial, participants will be randomized to receive 3 sessions of iTBS-s or iTBS-c, undergo a washout period of at least 2 weeks, then complete 3 sessions of the opposite iTBS intervention.

Participants will complete 5 study visits within the span of 2-3 months, including:

* Screening assessments to determine eligibility \& 1 sham iTBS (iTBS-sh) session to assess tolerability of the brain stimulation (Visit 1);
* 1 Magnetic Resonance Imaging (MRI) brain scan and randomization (Visit 2);
* Safety and clinical assessments, iTBS-s or iTBS-c intervention, TMS evoked electroencephalography (TMS-EEG) measurements, and post-iTBS questionnaires (Visits 3-5) followed by a washout period of at least 2 weeks;
* Safety and clinical assessments, the opposite iTBS-s or iTBS-c intervention originally randomized to, TMS-EEG measurements, and post-iTBS questionnaires (Visits 6-8).

Conditions

• Major Depressive Disorder (MDD)

Interventions

DEVICE

Spaced iTBS

Intermittent Theta-Burst Stimulation (iTBS) is a form of non-invasive brain stimulation that uses magnetic pulses applied to the scalp using a coil. iTBS will be used to stimulate the left dorsolateral prefrontal cortex (DLPFC) to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity. TMS-EEG will be performed to measure changes in brain plasticity throughout the trial. An EEG cap will be placed on the participant's head, and the electrodes on the cap will be filled with saline gel using a dull syringe. During the intervention, the study team will conduct a baseline TMS-EEG measurement consisting of single TMS pulses. Participants will then complete iTBS-s (experimental study intervention), which will be delivered to the left DLPFC. Following iTBS-s, post-iTBS TMS-EEG measurements will be obtained consisting of 3 TMS trains delivered to the left DLPFC (Post-0, Post-20, and Post-60 minutes).

DEVICE

Compressed iTBS

Intermittent Theta-Burst Stimulation (iTBS) is a form of non-invasive brain stimulation that uses magnetic pulses applied to the scalp using a coil. iTBS will be used to stimulate the left dorsolateral prefrontal cortex (DLPFC) to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity. TMS-EEG will be performed to measure changes in brain plasticity throughout the trial. An EEG cap will be placed on the participant's head, and the electrodes on the cap will be filled with saline gel using a dull syringe. During the intervention, the study team will conduct a baseline TMS-EEG measurement consisting of single TMS pulses. Participants will then complete iTBS-c (active comparator), which will be delivered to the left DLPFC. Following iTBS-c, post-iTBS TMS-EEG measurements will be obtained consisting of 3 TMS trains delivered to the left DLPFC (Post-0, Post-20, and Post-60 minutes).

Sponsors & Collaborators

• Brain Canada

  collaborator OTHER

• Centre for Addiction and Mental Health

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-30

Primary Completion

2026-01-31

Completion

2026-12-31

Countries

• Canada

Study Locations