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

NCT06152705 | Recruiting

• 1 other identifier: 2023-019
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Depressive Episode; Depression; Depressive Disorder, Major

Keywords

fMRI; iTBS; neuronavigation

Outcome Measures

Primary Outcomes (1)

• 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).

  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).

  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).

  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)

  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).

  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)

  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).]

Other Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  Daily Monday-Friday throughout study (6 weeks).

• Side Effects

  Daily Monday-Friday throughout study (6 weeks).

Study Arms (2)

fMRI guided iTBS targetting

EXPERIMENTAL

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

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.

Device: repetitive Transcranial Magnetic Stimulation

Interventions

repetitive Transcranial Magnetic Stimulation 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).

Also known as: rTMS, TMS, iTBS, TBS

Neuronavigation guided iTBS targetting; fMRI guided iTBS targetting

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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.

You may not qualify if:

• 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 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
• 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)

Sponsors & Collaborators

• The Royal Ottawa Mental Health Centre: lead

Study Sites (1)

The Royal's Institute of Mental Health Research

Ottawa, Ontario, K1Z 7K4, Canada

RECRUITING

Related Publications (6)

• 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.

  PMID: 15123391 BACKGROUND

• 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.

  PMID: 12369271 BACKGROUND

• 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.

  PMID: 27632386 BACKGROUND

• 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.

  PMID: 14978782 BACKGROUND

• 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.

  PMID: 16139808 BACKGROUND

• 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.

  PMID: 22658708 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Sara Tremblay, PhD

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

  PRINCIPAL INVESTIGATOR

• Lauri Tuominen, MD PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey Shim, MSc

CONTACT

613-722-6521; stacey.shim@theroyal.ca

Emma Cummings, BA

CONTACT

613-722-6521; emma.cummings@theroyal.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: December 1, 2023
• Study Start: September 16, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Once your data has been included in the OpenNeuro database, your data cannot be removed or withdrawn as we will be unable to identify your information to separate it from the database.
• Access Criteria: The shared data will hosted on the OpenNeuro (https://openneuro.org/) platform. The dataset becomes publically available under the Creative Commons Zero (CC0) Public Domain Dedication which places no restrictions on who can use the data or what can be done with them. The OpenNeuro is supported by the United States National Instututes of Mental Health BRAIN Initiative. The OpenNeuro follows the FAIR principles, which states that in order for shared data to be maximally useful for the scientific community, they need to be Findable, Accessible, Interoperable, and Reusable.

Locations

CA (1)