Comparing the Efficacy of fMRI-Guided vs. Standard iTBS in Treating Depression

NCT ID: NCT06152705

Last Updated: 2025-12-17

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

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-16

Study Completion Date

2027-10-01

Brief Summary

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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

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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

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Depression Depressive Disorder, Major Depressive Episode

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
This study is a two-arm triple-blind randomized parallel assignment clinical trial as neither the participant, care provider, nor the outcomes assessor know the arm (or condition) assigned to the participants. There are two treatment "arms" in which half will receive fMRI navigated iTBS and the other half will receive neuronavigated iTBS determined by a study randomizer software.

Master randomization list of treatment blinding will be kept by a scientist of the research centre that is not involved in the research project. This can be broken in case of emergency and they can then inform required medical professionals directly if necessary. Directly involved research staff will be blinded (including the PI).

Study Groups

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fMRI guided iTBS targetting

The target selected is based on functional connectivity determined from the MRI scan.

Group Type EXPERIMENTAL

repetitive Transcranial Magnetic Stimulation

Intervention Type DEVICE

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).

Neuronavigation guided iTBS targetting

A technique for treatment location targeting, based on structural images of the brain using standard coordinates.

Group Type ACTIVE_COMPARATOR

repetitive Transcranial Magnetic Stimulation

Intervention Type DEVICE

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).

Interventions

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repetitive Transcranial Magnetic Stimulation

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).

Intervention Type DEVICE

Other Intervention Names

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rTMS TMS iTBS TBS

Eligibility Criteria

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Inclusion Criteria

For inclusion in the study, participants must fulfill all the following criteria:

1. voluntary and competent to consent to study,
2. Adults aged 18 years old or older,
3. can speak and read English,
4. primary and/or predominant diagnosis of major depressive episode without psychotic features in the current episode (confirmed by a Mini-International Neuropsychiatric Interview),
5. depressive symptoms have not improved after ≥ 1 adequate dose of antidepressant trial in the current depressive episode,
6. 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),
7. have been referred to rTMS treatment by their treating physician, and took a free and informed decision to follow this treatment,
8. are able to adhere to treatment schedule,
9. have stable psychotropic medications (including prescribed cannabis) or psychotherapy regimen for at least four weeks prior to entering the trial,
10. have an education-adjusted score of ≥ 24 at the Mini-Mental State Evaluation (MMSE) if they are aged ≥ 65.

Exclusion Criteria

Participants fulfilling any of the following criteria will be excluded from the study:

1. diagnosis of bipolar I or II disorder, based on the DSM-5 criteria
2. 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.
3. current use of illegal substances or cannabis (unless medical use, see note below), confirmed by urine drug screen
4. have a concomitant major unstable medical or neurologic illness (e.g. uncontrolled diabetes or renal dysfunction),
5. organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician
6. acute suicidality or threat to life from self-neglect,
7. are pregnant or breastfeeding, or thinking of becoming pregnant during course of treatment (pregnancy will be assessed by a urine test),
8. have a specific contraindication for TMS (e.g., personal history of epilepsy or seizure, metallic head implant, pacemaker),
9. unwilling to maintain current antidepressant regimen,
10. are taking more than 1 mg of lorazepam per day or equivalent,
11. any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study,
12. any contraindications for MRI
13. 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Royal Ottawa Mental Health Centre

OTHER

Sponsor Role lead

Responsible Party

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Sara Tremblay

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sara Tremblay, PhD

Role: PRINCIPAL_INVESTIGATOR

The Royal&#39;s Institute of Mental Health Research

Lauri Tuominen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

The Royal&#39;s Institute of Mental Health Research

Locations

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The Royal's Institute of Mental Health Research

Ottawa, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Stacey Shim, MSc

Role: CONTACT

613-722-6521 ext. 6356

Emma Cummings, BA

Role: CONTACT

613-722-6521 ext. 6586

Facility Contacts

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Sara Tremblay, PhD

Role: primary

6137226521 ext. 6227

References

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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.

Reference Type BACKGROUND
PMID: 15123391 (View on PubMed)

Shajahan 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.

Reference Type BACKGROUND
PMID: 12369271 (View on PubMed)

Martin 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.

Reference Type BACKGROUND
PMID: 27632386 (View on PubMed)

Holtzheimer 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.

Reference Type BACKGROUND
PMID: 14978782 (View on PubMed)

Avery 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.

Reference Type BACKGROUND
PMID: 16139808 (View on PubMed)

Fox 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.

Reference Type BACKGROUND
PMID: 22658708 (View on PubMed)

Other Identifiers

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2023-019

Identifier Type: -

Identifier Source: org_study_id