DepressionNCT06152705
Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
A study testing repetitive Transcranial Magnetic Stimulation in people with Depression and Depressive Disorder, Major, run by The Royal Ottawa Mental Health Centre at 1 site in Canada.
Trial summary
In this triple-blind randomized controlled trial, we ask if targeting intermittent theta burst stimulation (iTBS) based on individual resting state connectivity improves treatment outcomes in major depressive disorder (MDD). For the trial, we will recruit 210 patients with major depressive disorder. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression, Depressive Disorder, Major, Depressive Episode
- What is being tested?
- repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteCanada
- Study dates
- 16 Sep 2024to 1 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the study, participants must fulfill all the following criteria:
- voluntary and competent to consent to study,
- Adults aged 18 years old or older,
- can speak and read English,
- primary and/or predominant diagnosis of major depressive episode without psychotic features in the current episode (confirmed by a Mini-International Neuropsychiatric Interview),
- depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode,
Show all 11Show fewer
- moderate symptoms in the current depressive episode as indexed by a score of at least 15 on the Grid 17-item Hamilton Rating Scale for Depression (Grid HRSD-17),
- have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment,
- are able to adhere to treatment schedule,
- have stable psychotropic medications (including prescribed cannabis) or psychotherapy regimen for at least four weeks prior to entering the trial,
- have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if they are aged ≥ 65.
Who cannot join
- Participants fulfilling any of the following criteria will be excluded from the study:
- diagnosis of bipolar I or II disorder, based on the DSM-5 criteria
- current or past (< 3 months) substance (excluding caffeine or nicotine) or alcohol use disorder, as defined in DSM-5 criteria. Based on the DSM-5 criteria, mild cannabis or alcohol use disorder would be permissible in the past 3 months, moderate to severe would be an exclusion.
- current use of illegal substances or cannabis (unless medical use, see note below), confirmed by urine drug screen
- have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction),
- organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician
Show all 14Show fewer
- acute suicidality or threat to life from self-neglect,
- are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment (pregnancy will be assessed by a urine test),
- have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker),
- unwilling to maintain current antidepressant regimen,
- are taking more than 1 mg of lorazepam per day or equivalent,
- any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study,
- any contraindications for MRI
- have failed a course of ECT within the current depressive episode due to the lower likelihood of response to rTMS (if they have had failed ECT in the past, this does not exclude them)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
The Royal's Institute of Mental Health Research
Ottawa, Ontario, K1Z 7K4
Sara Tremblay, PhD, 6137226521 ext. 6227, Sara.Tremblay@theroyal.ca
About this study
Official title: Triple-blind Randomized Trial Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
In this triple-blind randomized controlled trial, we ask if targeting intermittent theta burst stimulation (iTBS) based on individual resting state connectivity improves treatment outcomes in major depressive disorder (MDD). For the trial, we will recruit 210 patients with major depressive disorder. Each patient will undergo a 30-40-minute MRI scan, after which they will receive a 6-week standard iTBS treatment. Participants will be randomized to receive iTBS either to the standard neuronavigated target (a technique for treatment location targeting, based on group-average connectivity) or to a personalized connectivity-guided target selected based on individual functional connectivity scans. The main outcome of this trial is response rate as determined by ≥ 50% reduction in Grid HRSD-17 scores. Secondary outcomes include remission rate, change in depression, anxiety and anhedonia symptoms, quality of life, and biological measures of heart rate variability, objective sleep measures and daily activity as a proxy of anhedonia - defined as a reduced ability to experience pleasure.
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved and widely used focal, safe, well-tolerated, and non-invasive brain stimulation method for the treatment of depression, and has been approved in Canada. Typical clinical rTMS is delivered on the left dorsolateral prefrontal cortex (DLPFC) at a 10 Hz frequency over 30-45 minutes to induce an increase in cortical excitability, which outlasts the duration of stimulation. iTBS is a novel refinement of conventional rTMS. iTBS consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz). However, instead of 30 minute treatment sessions, iTBS has comparable clinical efficacy with only 3 minute treatment sessions. Currently roughly 50% of the people receiving rTMS treatment for depression respond to the treatment. One of the main goals of current research in rTMS is to find improvements in the protocol to increase the number of responders.
One of the potential ways to improve rTMS is to select the target based on individual resting state functional connectivity. Within the DLPFC, there are still several possible targets for the rTMS. Functional magnetic resonance imaging (fMRI) studies have shown that therapeutic effects of rTMS are related to its effects on the subgenual anterior cingulate cortex (sgACC; Broadman area 25). Past literature has shown that in MDD the effectiveness of a target is related to its connectivity with the sgACC. A recent study showed in a retrospective sample of MDD patients that response to rTMS correlates with the distance from the personalized connectivity-guided target rather than a group average target, opening the door for individualized connectivity-guided rTMS targeting. Yet, the question whether individualized connectivity-guided rTMS targeting improves rTMS outcomes in a prospective sample has never been investigated. In this two-arm triple-blind randomized parallel assignment clinical trial we will test if 6-week treatment using individualized connectivity-guided iTBS targeting leads to better outcomes in MDD compared to conventional neuronavigated iTBS.
- Conditions
- Depression, Depressive Disorder, Major, Depressive Episode
- Being tested
- repetitive Transcranial Magnetic Stimulation
- Keywords
- fMRI, iTBS, neuronavigation
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive Transcranial Magnetic StimulationDevice
Also called rTMS, TMS, iTBS, TBS
Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Typical treatments involve 30 to 45 minutes daily sessions delivered over 4 to 6 weeks. Recent technical advances allowed the development of theta burst stimulation (TBS), a novel rTMS paradigm that reduces daily sessions to 3 to 4 minutes while maintaining the same clinical efficacy. This study will specifically be administering intermittent TBS (iTBS), which is a novel refinement of conventional rTMS and consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz).
| Study group | Role | What they receive |
|---|---|---|
| fMRI guided iTBS targetting | Experimental | The target selected is based on functional connectivity determined from the MRI scan. Receives: Device: repetitive Transcranial Magnetic Stimulation |
| Neuronavigation guided iTBS targetting | Active comparator | A technique for treatment location targeting, based on structural images of the brain using standard coordinates. Receives: Device: repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response.
Clinical response will be defined as a ≥ 50% reduction in the 17-Item Grid Hamilton Rating Scale for Depression (GRID-HRSD-17). The Grid HRSD is a clinician-rated instrument with seventeen items used to measure the severity of depressive episodes. Remission will be defined as a HRSD-17 score < 8 after 6 weeks of treatment.
Score scale from 0 (better outcome, no depression thus better clinical response) to 60 (worst outcome, extreme depression thus worse clinical response).
Measured: Administered at baseline (prior to first iTBS treatment) and every 2 weeks after that for 6 weeks (week 2, week 4, and week 6).
Secondary outcomes (15)
Change in severity of clinician-rated depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 52 (worst outcome, extreme depression).
Measured: Administered at screening, before the first iTBS, week 2, week 4 and after iTBS treatment (week 6).
Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II).
As a secondary measure of depressive symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme depression).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI)
As a secondary measure of anxiety symptoms. Score scale from 0 (better outcome, no depression) to 63 (worst outcome, extreme anxiety).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS).
To assess the effect of treatment on suicidal thoughts that may be improved by iTBS.
Score scale from 0 (better outcome, no desire for suicide) to 38 (worst outcome, extreme desire for suicide).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported sleep quality as measured by Leeds Sleep Evaluation Questionnaire (LSEQ)
To assess the effect of treatment on self-report sleep that may be improved by iTBS.
Score scale from 0 (better outcome, excellent sleep) to 100 (worst outcome, extremely poor sleep).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported sleep patterns as measured by Pittsburgh Sleep Quality Index (PSQI)
To assess the effect of treatment on self-report sleep that may be improved by iTBS.
Score scale from 0 (better outcome, very high quality sleep) to 21 (worst outcome, very low quality sleep).
Measured: Before the first iTBS and after treatment (6 weeks).
Change in quantity of sleep as measured with Empatica EmbracePlus Smartwatch
To assess the effect of treatment on objective measures of sleep patterns that may be improved by iTBS.
Measured: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit
Change in perceived stress as measures with Perceived stress scale (PSS)
To assess the effect of treatment on self-report measures of stress that may be improved by iTBS.
Score scale from 0 (better outcome, no perceived stress) to 40 (worst outcome, extreme perceived stress).
Measured: Administered at baseline before first iTBS treatment and after treatment completion (week 6).
Change in physiological stress based on pulse rate and electrodermal activity response as measured with Empatica EmbracePlus Smartwatch
To assess the effect of treatment on objective measures of stress that may be improved by iTBS.
Measured: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit
Change in self-reported anhedonia as measured by Snaith-Hamilton Pleasure Scale (SHAPS)
To assess the effect of treatment on self-report measures of anhedonia symptoms that may be improved by iTBS.
Score scale from 0 (better outcome, no anhedonia) to 14 (worst outcome, extreme anhedonia).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in motion intensity (based on number of steps and total activity) as measured with Empatica EmbracePlus Smartwatch
To assess the effect of treatment on objective measures of physical activity that may be improved by iTBS.
Measured: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit.
Change in motion heart rate variability as measured with Empatica EmbracePlus Smartwatch
To assess the effect of treatment on objective measures of heart-rate variability, which has been shown to be linked to MDD and that may be improved by iTBS.
Measured: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit.
Change in self-reported hopelessness as measured by Beck Hopelessness Scale (BHS)
To assess the effect of treatment on self-report symptoms of hopelessness that may be improved by iTBS.
Score scale from 0 (better outcome, no sense of hopelessness) to 20 (worst outcome, extreme sense of hopelessness).
Measured: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).
Change in quality of life as measured with Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
To assess the effect of treatment on self-report measures of quality of life that may be improved by iTBS.
Score scale from 0 (worse outcome, poor life satisfaction and poor life quality) to 70 (better outcome, high life satisfaction and high quality of life).
Measured: Time Frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).
Change in well-being as measured with Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)
To assess the effect of treatment on self-report measures of well-being that may be improved by iTBS.
Score scale from 14 (worse outcome, poor mental wellbeing) to 70 (better outcome, excellent mental well).
Measured: Administered before the first iTBS, week 2, week 4 and after iTBS treatment (week 6).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2023
- Study start16 Sep 2024
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Royal Ottawa Mental Health Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sara Tremblay, The Royal Ottawa Mental Health Centre
- Investigators
- Sara Tremblay, PhD, Principal investigator, The Royal's Institute of Mental Health ResearchLauri Tuominen, MD PhD, Principal investigator, The Royal's Institute of Mental Health Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06152705
- Sponsor's protocol ID
- 2023-019
- Status last verified
- Dec 2025
- First submitted
- 18 Sep 2023
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After participants have completed their participation, we will ask them for informed consent for the storage of their de-identified data on OpenNeuro (an open access database) for the purpose of unspecified research for unspecified future research. If they do agree to participate, they will be given a unique study code (different from the participant ID used in the previous study) will be assigned to all of your study data instead of your personal identifying information (ex. 'John Smith' replaced by the unique study code 'A283422'). This unique study code will be used in the Open Access database to ensure your privacy and confidentiality (i.e. your de-identified study data cannot be linked to you in any way). In addition to an unique study code, their de-identified study data used in the Open Access database will include: * Age, sex, handedness, education level * Medical diagnosis and medication * Summary scores from clinical interviews * MRI scans * Treatment allocation
Publications
Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, Hess CW, Fisch HU, Schlaepfer TE. Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Psychiatry Res. 2004 Apr 30;126(2):123-33. doi: 10.1016/j.psychres.2003.10.006.
PubMed 15123391Shajahan PM, Glabus MF, Steele JD, Doris AB, Anderson K, Jenkins JA, Gooding PA, Ebmeier KP. Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jun;26(5):945-54. doi: 10.1016/s0278-5846(02)00210-5.
PubMed 12369271Martin DM, McClintock SM, Forster J, Loo CK. Does Therapeutic Repetitive Transcranial Magnetic Stimulation Cause Cognitive Enhancing Effects in Patients with Neuropsychiatric Conditions? A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Neuropsychol Rev. 2016 Sep;26(3):295-309. doi: 10.1007/s11065-016-9325-1. Epub 2016 Sep 8.
PubMed 27632386Holtzheimer PE 3rd, Russo J, Claypoole KH, Roy-Byrne P, Avery DH. Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. Depress Anxiety. 2004;19(1):24-30. doi: 10.1002/da.10147.
PubMed 14978782Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor DR, Claypoole KH, Wajdik C, Roy-Byrne P. A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biol Psychiatry. 2006 Jan 15;59(2):187-94. doi: 10.1016/j.biopsych.2005.07.003. Epub 2005 Sep 1.
PubMed 16139808Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
PubMed 22658708
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Triple-blind Randomized Trial Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression
- ClinicalTrials.gov ID
- NCT06152705
- Acronym / sponsor ID
- 2023-019
- Conditions
- Depression, Depressive Disorder, Major, Depressive Episode
- Keywords
- fMRI, iTBS, neuronavigation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- The Royal Ottawa Mental Health CentreUniversity, hospital or other
- Study start
- 16 Sep 2024 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 1 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this triple-blind randomized controlled trial, we ask if targeting intermittent theta burst stimulation (iTBS) based on individual resting state connectivity improves treatment outcomes in major depressive disorder (MDD). For the trial, we will recruit 210 patients with major depressive disorder. Each patient will undergo a 30-40-minute MRI scan, after which they will receive a 6-week standard iTBS treatment. Participants will be randomized to receive iTBS either to the standard neuronavigated target (a technique for treatment location targeting, based on group-average connectivity) or to a personalized connectivity-guided target selected based on individual functional connectivity scans. The main outcome of this trial is response rate as determined by ≥ 50% reduction in Grid HRSD-17 scores. Secondary outcomes include remission rate, change in depression, anxiety and anhedonia symptoms, quality of life, and biological measures of heart rate variability, objective sleep measures and daily activity as a proxy of anhedonia - defined as a reduced ability to experience pleasure.
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved and widely used focal, safe, well-tolerated, and non-invasive brain stimulation method for the treatment of depression, and has been approved in Canada. Typical clinical rTMS is delivered on the left dorsolateral prefrontal cortex (DLPFC) at a 10 Hz frequency over 30-45 minutes to induce an increase in cortical excitability, which outlasts the duration of stimulation. iTBS is a novel refinement of conventional rTMS. iTBS consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz). However, instead of 30 minute treatment sessions, iTBS has comparable clinical efficacy with only 3 minute treatment sessions. Currently roughly 50% of the people receiving rTMS treatment for depression respond to the treatment. One of the main goals of current research in rTMS is to find improvements in the protocol to increase the number of responders.
One of the potential ways to improve rTMS is to select the target based on individual resting state functional connectivity. Within the DLPFC, there are still several possible targets for the rTMS. Functional magnetic resonance imaging (fMRI) studies have shown that therapeutic effects of rTMS are related to its effects on the subgenual anterior cingulate cortex (sgACC; Broadman area 25). Past literature has shown that in MDD the effectiveness of a target is related to its connectivity with the sgACC. A recent study showed in a retrospective sample of MDD patients that response to rTMS correlates with the distance from the personalized connectivity-guided target rather than a group average target, opening the door for individualized connectivity-guided rTMS targeting. Yet, the question whether individualized connectivity-guided rTMS targeting improves rTMS outcomes in a prospective sample has never been investigated. In this two-arm triple-blind randomized parallel assignment clinical trial we will test if 6-week treatment using individualized connectivity-guided iTBS targeting leads to better outcomes in MDD compared to conventional neuronavigated iTBS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fMRI guided iTBS targetting | Experimental | Device: repetitive Transcranial Magnetic StimulationThe target selected is based on functional connectivity determined from the MRI scan. |
| Neuronavigation guided iTBS targetting | Active comparator | Device: repetitive Transcranial Magnetic StimulationA technique for treatment location targeting, based on structural images of the brain using standard coordinates. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- voluntary and competent to consent to study,
- Adults aged 18 years old or older,
- can speak and read English,
- primary and/or predominant diagnosis of major depressive episode without psychotic features in the current episode (confirmed by a Mini-International Neuropsychiatric Interview),
- depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode,
Key exclusion criteria (14 listed)
- diagnosis of bipolar I or II disorder, based on the DSM-5 criteria
- current or past (< 3 months) substance (excluding caffeine or nicotine) or alcohol use disorder, as defined in DSM-5 criteria. Based on the DSM-5 criteria, mild cannabis or alcohol use disorder would be permissible in the past 3 months, moderate to severe would be an exclusion.
- current use of illegal substances or cannabis (unless medical use, see note below), confirmed by urine drug screen
- have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction),
- organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| repetitive Transcranial Magnetic StimulationAlso: rTMS, TMS, iTBS, TBSRepetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Typical treatments involve 30 to 45 minutes daily sessions delivered over 4 to 6 weeks. Recent technical advances allowed the development of theta burst stimulation (TBS), a novel rTMS paradigm that reduces daily sessions to 3 to 4 minutes while maintaining the same clinical efficacy. This study will specifically be administering intermittent TBS (iTBS), which is a novel refinement of conventional rTMS and consists of bursts of 3 stimulations at 50 Hz at theta frequency (5 Hz). | Device | Neuronavigation guided iTBS targetting, fMRI guided iTBS targetting |
Primary outcome
Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response.
Time frame: Administered at baseline (prior to first iTBS treatment) and every 2 weeks after that for 6 weeks (week 2, week 4, and week 6).
Clinical response will be defined as a ≥ 50% reduction in the 17-Item Grid Hamilton Rating Scale for Depression (GRID-HRSD-17). The Grid HRSD is a clinician-rated instrument with seventeen items used to measure the severity of depressive episodes. Remission will be defined as a HRSD-17 score < 8 after 6 weeks of treatment. Score scale from 0 (better outcome, no depression thus better clinical response) to 60 (worst outcome, extreme depression thus worse clinical response).
15 secondary outcomes
Change in severity of clinician-rated depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
Time frame: Administered at screening, before the first iTBS, week 2, week 4 and after iTBS treatment (week 6).
Change in self-reported depression symptoms as measured by Beck Depression Inventory (BDI-II).
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported anxiety symptoms as measured by Beck Anxiety Inventory (BAI)
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported suicidal thoughts symptoms as measured by Beck Scale for Suicidal Ideation (BSS).
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported sleep quality as measured by Leeds Sleep Evaluation Questionnaire (LSEQ)
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in self-reported sleep patterns as measured by Pittsburgh Sleep Quality Index (PSQI)
Time frame: Before the first iTBS and after treatment (6 weeks).
Change in quantity of sleep as measured with Empatica EmbracePlus Smartwatch
Time frame: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit
Change in perceived stress as measures with Perceived stress scale (PSS)
Time frame: Administered at baseline before first iTBS treatment and after treatment completion (week 6).
Change in physiological stress based on pulse rate and electrodermal activity response as measured with Empatica EmbracePlus Smartwatch
Time frame: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit
Change in self-reported anhedonia as measured by Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).]
Change in motion intensity (based on number of steps and total activity) as measured with Empatica EmbracePlus Smartwatch
Time frame: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit.
Change in motion heart rate variability as measured with Empatica EmbracePlus Smartwatch
Time frame: Start 2 weeks before the planned start date. Continuous measurement throughout study until the 2-week follow-up visit.
Change in self-reported hopelessness as measured by Beck Hopelessness Scale (BHS)
Time frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).
Change in quality of life as measured with Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF)
Time frame: Time Frame: Administered at baseline (prior to first iTBS treatment) and every week after that for 6 weeks (week 1, week 2, week 3, week 4, week 5, week 6).
Change in well-being as measured with Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)
Time frame: Administered before the first iTBS, week 2, week 4 and after iTBS treatment (week 6).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Background: PubMed 15123391Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, Hess CW, Fisch HU, Schlaepfer TE. Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Psychiatry Res. 2004 Apr 30;126(2):123-33. doi: 10.1016/j.psychres.2003.10.006.
- Background: PubMed 12369271Shajahan PM, Glabus MF, Steele JD, Doris AB, Anderson K, Jenkins JA, Gooding PA, Ebmeier KP. Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jun;26(5):945-54. doi: 10.1016/s0278-5846(02)00210-5.
- Background: PubMed 27632386Martin DM, McClintock SM, Forster J, Loo CK. Does Therapeutic Repetitive Transcranial Magnetic Stimulation Cause Cognitive Enhancing Effects in Patients with Neuropsychiatric Conditions? A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Neuropsychol Rev. 2016 Sep;26(3):295-309. doi: 10.1007/s11065-016-9325-1. Epub 2016 Sep 8.
- Background: PubMed 14978782Holtzheimer PE 3rd, Russo J, Claypoole KH, Roy-Byrne P, Avery DH. Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. Depress Anxiety. 2004;19(1):24-30. doi: 10.1002/da.10147.
- Background: PubMed 16139808Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor DR, Claypoole KH, Wajdik C, Roy-Byrne P. A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biol Psychiatry. 2006 Jan 15;59(2):187-94. doi: 10.1016/j.biopsych.2005.07.003. Epub 2005 Sep 1.
- Background: PubMed 22658708Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
- Individual participant dataSharing planned: Yes. After participants have completed their participation, we will ask them for informed consent for the storage of their de-identified data on OpenNeuro (an open access database) for the purpose of unspecified research for unspecified future research. If they do agree to participate, they will be given a unique study code (different from the participant ID used in the previous study) will be assigned to all of your study data instead of your personal identifying information (ex. 'John Smith' replaced by the unique study code 'A283422'). This unique study code will be used in the Open Access database to ensure your privacy and confidentiality (i.e. your de-identified study data cannot be linked to you in any way). In addition to an unique study code, their de-identified study data used in the Open Access database will include: * Age, sex, handedness, education level * Medical diagnosis and medication * Summary scores from clinical interviews * MRI scans * Treatment allocation
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sara Tremblay, PhD principal investigator
The Royal's Institute of Mental Health Research
Lauri Tuominen, MD PhD principal investigator
The Royal's Institute of Mental Health Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive Transcranial Magnetic Stimulation in people with Depression and Depressive Disorder, Major, run by The Royal Ottawa Mental Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stacey Shim, MSc (613-722-6521 ext. 6356, stacey.shim@theroyal.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare the efficacy of fMRI guided TMS and conventional neuronavigated TMS on clinical response. (time frame: Administered at baseline (prior to first iTBS treatment) and every 2 weeks after that for 6 weeks (week 2, week 4, and week 6).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06152705, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.