Impact of Spaced iTBS on Plasticity in the Motor Cortex (STEP-MC)

February 2, 2026 updated by: Centre for Addiction and Mental Health

Spaced iTBS: Effects on Plasticity in the Motor Cortex

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 in healthy, right-handed individuals aged 18 to 50 years. 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. Sham iTBS (iTBS-sh) will be used as a control to make the results of the study more reliable.

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

  • Screening assessments to determine eligibility (Visit 1);
  • Calibration iTBS session (Visit 2) to assess tolerability of brain stimulation;
  • Three experimental iTBS sessions (iTBS-s, iTBS-c, and iTBS-sh) in a randomized order (Visits 3-5), each separated by at least 72 hours. During each session, the study team will stimulate the motor cortex and record the muscle activity of your hand to measure changes in brain plasticity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Major Depressive Disorder (MDD) is a mental illness affecting millions of individuals worldwide and in Canada, and is a leading cause of morbidity, mortality, and disability. While antidepressant medications are effective in treating MDD, their efficacy is moderate and systemic side-effects persist, such as sexual dysfunction, drowsiness, weight gain, and dry mouth. Thus, more effective treatments are needed for MDD.

Neuroimaging techniques have implicated the dysregulation of brain plasticity in depression. In particular, long-term potentiation (LTP)-like activity in the dorsolateral prefrontal cortex (DLPFC) and the motor cortex is known to be impaired in MDD. As such, transcranial magnetic stimulation (TMS)-based interventions, which aim to modify underlying cortical activity, are now established treatments of depression. Intermittent theta-burst stimulation (iTBS), a novel form of repetitive TMS approved by the US Food and Drug Administration (FDA) for the treatment of depression, delivers intermittent, high-frequency theta bursts. It has been demonstrated to induce sustained plasticity in the DLPFC and the motor cortex. Although iTBS is approved for the treatment of depression, response and remission rates for MDD are still relatively low.

Based on promising research conducted in the hippocampus of rodents, the investigators believe that modifying some parameters of the iTBS protocol may be more effective in inducing plasticity than the currently used iTBS protocol. Thus, in this trial researchers aim to optimize iTBS and its effects on cortical plasticity as a first step towards optimizing it for the treatment of depression.

The primary and secondary objectives and hypotheses of the study are as follows:

Objective 1: To compare the effect of compressed iTBS (iTBS-c) to spaced iTBS (iTBS-s) on LTP-like activity (referred to hereafter as iTBS-LTP) as measured using motor evoked potentials (MEPs) recorded from the right abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first dorsal interosseous (FDI) muscles.

Hypothesis 1: iTBS-s will elicit larger iTBS-LTP post-iTBS as compared to iTBS-c.

Objective 2: To compare the effect of iTBS-c and iTBS-s on iTBS-LTP relative to iTBS-sh.

Hypothesis 2: iTBS-c and iTBS-s will elicit larger iTBS-LTP post-iTBS as compared to iTBS-sh.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M6J 1H4
        • Centre for Addiction and Mental Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Age 18 years or above, and less than 51 years.
  2. Right handedness, assessed using the Edinburgh Handedness Inventory (EHI).
  3. Sufficiently proficient in English to complete the required study assessments, as per investigator judgement.
  4. Willingness and capacity to provide informed consent.
  5. Willingness to comply with all study procedures.

Exclusion Criteria:

  1. Age 17 years or less, or greater than 51 years, as brain plasticity is known to be affected by age.
  2. Current use of any psychotropic medications (e.g. anti-depressants, anti-convulsants, anti-psychotics, etc.).
  3. Contraindications to transcranial magnetic stimulation (TMS), as per investigator judgment.
  4. Lifetime history of any Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis, assessed using the Structured Clinical Interview for DSM-5 (SCID-5), except simple phobias.
  5. Left handed or ambidextrous, assessed using the EHI, to minimize the heterogeneity in cortical excitability and plasticity.
  6. Self-reported history of seizures and/or other major neurological conditions, as per investigator judgement, due to the risk of seizures associated with TMS in individuals with a heightened risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Compressed iTBS
After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-c condition in a randomized order during Visits 3 to 5. iTBS-c is the active comparator.
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 motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity.

During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-c (active comparator), which will be delivered unilaterally to the left motor cortex. Following iTBS-c, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation.

The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Other Names:
  • iTBS-c
Experimental: Spaced iTBS
After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-s condition in a randomized order during Visits 3 to 5. iTBS-s is the experimental study intervention.
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 motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity.

During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-s (experimental study intervention), which will be delivered unilaterally to the left motor cortex. Following iTBS-s, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation.

The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Other Names:
  • iTBS-s
Sham Comparator: Sham iTBS
After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-sh condition in a randomized order during Visits 3 to 5. iTBS-sh is the sham comparator.
Device: Sham 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 motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity.

During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-sh (sham comparator), which will be delivered unilaterally to the left motor cortex. Following iTBS-sh, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation.

The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Other Names:
  • iTBS-sh

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
iTBS-LTP
Time Frame: Up to 3 months

The primary outcome measure is iTBS-induced LTP (iTBS-LTP), which will be calculated at each post-iTBS time points (Post-0, Post-15, Post-30, Post-45 and Post-60).

At each time point, the mean or median MEP amplitude will be divided by the mean or median MEP amplitude across the two pre-iTBS TMS measurements (Pre-30 and Pre-15) for the corresponding iTBS condition. This will be repeated for all three iTBS conditions to generate iTBS-LTP values at the five post-iTBS time points. Larger iTBS-LTP values are indicative of stronger plasticity following the intervention.

This will address hypothesis 1, which examines whether iTBS-s induces stronger iTBS-LTP compared to iTBS-c, and hypothesis 2, which evaluates whether iTBS-s and iTBS-c induce stronger iTBS-LTP compared to iTBS-sh.
Up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 13, 2024

Primary Completion (Actual)

February 1, 2026

Study Completion (Actual)

February 1, 2026

Study Registration Dates

First Submitted

November 22, 2024

First Submitted That Met QC Criteria

December 11, 2024

First Posted (Actual)

December 16, 2024

Study Record Updates

Last Update Posted (Actual)

February 4, 2026

Last Update Submitted That Met QC Criteria

February 2, 2026

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2023/218

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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