Comparing Spaced iTBS with Compressed iTBS for major depressive disorder (MDD)
Official title: Theta-Burst Stimulation to Treat Depression
Optimization of Prefrontal Theta-Burst Stimulation to Treat Depression: A Bench to First-in-Human Study
Interventions
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).
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).
Canadian Sites (1)
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
Eligibility Criteria
See who this study is looking for14 criteria
The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.
Inclusion
- +Aged 18-50 years old;
- +Must meet criteria for a current Major Depressive Episode (MDE) as ascertained using the Structured Clinical Interview for DSM 5 (SCID-5);
- +Hamilton Rating Scale for Depression (HRSD-17) score \> 7;
- +Must be on a stable antidepressant regimen for a minimum of 4 weeks prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →, if currently taking antidepressants;
- +Right handed or ambidextrous, assessed using the Edinburgh Handedness Inventory (EHI);
- +Sufficiently proficient in English to complete the required study assessments, as per investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → judgement;
- +Willingness and capacity to provide informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →;
- +Willingness to comply with all study procedures.
Exclusion
- −Age 17 years or less, or greater than 51 years old, as brain plasticity is known to be affected by age;
- −Presence of any DSM-5 diagnosis (other than MDD), known to be associated with prefrontal cortical dysfunction, including lifetime diagnoses of bipolar disorder, intellectual disability, or a psychotic disorder, assessed using the SCID-5 and as per investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → judgement;
- −Presence of acute suicidal intent, as determined by the Scale for Suicidal Ideation (SSI);
- −Left handed, assessed using the EHI, to minimize the heterogeneity in cortical excitability and plasticity;
- −Current antipsychotic, antiepileptic, or benzodiazepine use given their potential effects on cortical plasticity, as ascertained through a medication review. An exception will be made if they are taking gabapentin or pregabalin prescribed only for chronic pain, and if the dose had been stable for at least 4 weeks prior to study enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
- −Contradictions to MRI or TMS (e.g., cardiac pacemaker, acoustic device, history of seizures, pregnancy), assessed using the MRI Safety Form and TMS Adult Safety Screen (TASS) and as per investigator judgement;
In plain language
Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.
What this study is
This study is investigating how something functions in the body, rather than testing a treatment directly.
Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → — an early safety study in a small group, checking how it is tolerated and at what dose.
What is being given or done in this study: Spaced iTBS, Compressed iTBS.
From the trial registry
Built from these fields:
- designModule.designInfo.primaryPurpose
- designModule.phases
- armsInterventionsModule.interventions[].name
How the study is run
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
You, the study team, and the people analysing the results would all be kept unaware of which group you are in until the study ends.
From the trial registry
Built from these fields:
- designModule.designInfo.allocation
- designModule.designInfo.maskingInfo.masking
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
One group receives an existing treatment, so the two can be compared.
There are 2 groups in this study.
From the trial registry
Built from this field:
- armsInterventionsModule.armGroups[].type
Who the study is looking for
The study lists an age range of 18 years to 50 years.
The study is open to people of any sex.
The study does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
These are the criteria the study lists. Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part.
From the trial registry
Built from these fields:
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How big and how long
The study aims to enrol about 84 people.
The study is currently expected to finish around December 2026.
The main measurement is taken over: Immediately before iTBS and at 20 and 60 minutes post-iTBS at Visit 3.
From the trial registry
Built from these fields:
- designModule.enrollmentInfo.count
- statusModule.completionDateStruct.date
- outcomesModule.primaryOutcomes[].timeFrame
What the study measures
DLPFC LTP-like Activity - CEA Ratio at Visit 3 — measured over Immediately before iTBS and at 20 and 60 minutes post-iTBS at Visit 3.
DLPFC LTP-like Activity - Change in pre-iTBS CEA from Visit 3 to 4 — measured over Pre-iTBS at BaselineBaselineYour starting measurements, taken before treatment begins.Read more → (Visit 3) and Pre-iTBS at 24 hours post-baseline (Visit 4).
DLPFC LTP-like Activity - Change in pre-iTBS CEA from Visit 4 to 5 — measured over Pre-iTBS at 24 hours post-baseline (Visit 4) and Pre-iTBS at 6 days post-baseline (Visit 5).
From the trial registry
Built from these fields:
- outcomesModule.primaryOutcomes[].measure
- outcomesModule.primaryOutcomes[].timeFrame
Source: NCT07033780 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.
Not medical advice. What do these terms mean?
What is being tested — in plain terms
About Spaced iTBSDevice
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).
From the trial registry — its own words, unedited.
What a device is here: A physical instrument, implant, app or piece of equipment being studied.
Read the full explanation → · in clinical review
About Compressed iTBSDevice
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).
From the trial registry — its own words, unedited.
What a device is here: A physical instrument, implant, app or piece of equipment being studied.
Read the full explanation → · in clinical review
Common questions
Answered from this trial’s registry record. Where the record doesn’t say, these answers say so rather than filling the gap.
Am I eligible for this trial?
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can decide whether someone can take part. Concord cannot make that determination, and neither can any tool that has not examined you.
What the study lists: an age range of 18 years to 50 years.
The full inclusionInclusion criteriaThe things you must have or be for a study to consider you.Read more → and exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → are published on this page, exactly as the study team wrote them.
The useful next step is to bring this trial to your doctor. Answering a few questions first gives them something concrete to review.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.eligibilityCriteria
Is there a placebo?
This study does not list a placeboPlaceboA dummy treatment with no active medicine, used for comparison.Read more → group.
One group receives an existing treatment so the two can be compared.
From the trial registry
- armsInterventionsModule.armGroups[].type
Would I know which treatment I am getting?
You, the study team, and the people analysing the results would all be kept unaware of which group you are in until the study ends.
Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.
From the trial registry
- designModule.designInfo.maskingInfo.masking
- designModule.designInfo.allocation
Who can join?
The study lists an age range of 18 years to 50 years.
It is open to people of any sex.
It does not accept healthy volunteersHealthy volunteerSomeone without the condition being studied who takes part anyway.Read more →.
Only the trial siteTrial siteA hospital or clinic where a study is actually run.Read more → can confirm whether a particular person can take part.
From the trial registry
- eligibilityModule.minimumAge
- eligibilityModule.maximumAge
- eligibilityModule.sex
- eligibilityModule.healthyVolunteers
How long would this take?
The study's main measurement is taken over: Immediately before iTBS and at 20 and 60 minutes post-iTBS at Visit 3.
The study as a whole is currently expected to finish around 2026-12.
How long any one person takes part can differ from the study length. The study team can tell you what the schedule looks like in practice.
From the trial registry
- outcomesModule.primaryOutcomes[].timeFrame
- statusModule.completionDateStruct.date
How many people are taking part?
The study aims to enrol about 84 people.
From the trial registry
- designModule.enrollmentInfo.count
Where is this happening?
This study lists one location: Toronto, Ontario, Canada.
Sites can open and close during a study, so confirm with the team before travelling.
From the trial registry
- trial_locations
About This Trial
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).
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See if this trial could fit youThis page is for informational purposes only and does not constitute medical advice. Clinical trial eligibility can only be determined by the trial site after proper screening. Trial information is sourced from ClinicalTrials.gov and may not reflect the most current status. Always consult your healthcare provider before making decisions about clinical trial participation.