Major Depressive DisorderNCT05813093
Interleaved TMS-fMRI in Ultra-treatment Resistant Depression
A study testing rTMS in people with Major Depressive Disorder, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
This is a study that will recruit patients from the neurosurgery clinic and the regular TMS clinic. It's a smaller study designed to collect brain imaging pre-treatment and then use image guided TMS to treat patient with a one week "accelerated" rTMS protocol using the research TMS machine that is housed in Dr. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteCanada
- Study dates
- 27 Sep 2023to 7 Jul 2025
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 20-65
- Have a diagnosis of MDD or persistent depressive disorder and meet criteria for a major depressive episode (moderate-severe) according to the DSM 5.0 with a 17-item Hamilton Rating Scale Score in Depression (HRSD-17) of >=18
- UTRD subjects will also have a duration of depressive symptoms >=5 years, treatment resistance to antidepressants will be defined by Maudsley-staging, failing >6 antidepressants (level 4) and >1 adjunctive antidepressants of adequate dose/duration, failed at >=1 psychotherapy, and no response to >=1 trial of esketamine, IV ketamine, ECT or rTMS
- Milder TRD participants will have failed at least 1 antidepressant medication of adequate dose/duration and never had neuromodulation treatment
Who cannot join
- Contraindications to MRI
- Medical/psychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern
- History of psychosis, pregnancy, substance dependence within the last 6 months
- Active neurological disorder
- History of seizure disorder
- Cognitive impairment
- Unable to provide informed consent on their own
- Pregnant
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
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N3M5
aNUSHA Basakran, PhD, 416-480-6100 ext. 61650, anusha.baskaran@sunnybrook.ca
About this study
Official title: Interleaved TMS-fMRI to Evaluate Intermittent Theta-burst and Dorsolateral Prefrontal Circuit Engagement in Ultra-treatment Resistant Depression
This is a study that will recruit patients from the neurosurgery clinic and the regular TMS clinic. It's a smaller study designed to collect brain imaging pre-treatment and then use image guided TMS to treat patient with a one week "accelerated" rTMS protocol using the research TMS machine that is housed in Dr. Sean Nestor's lab. The idea is to examine whether severe treatment resistant depression has a different brain signature than less severe/TRD and whether the investigators can get a therapeutic response from patients that would otherwise undergo neurosurgery or will ultimately undergo neurosurgery.
Read the detailed description
The objective of this study is to assess plasticity in both whole brain connectivity and a mood/affective circuit involving the dorsolateral prefrontal cortex (DLPFC) in individuals undergoing repetitive transcranial magnetic stimulation (rTMS) for treatment of ultra-treatment resistant depression. Our second aim is to explore how these markers predict response to rTMS. The DLPFC is a brain region known to support mood regulation and has functional brain activity that is altered in depression. Past evidence from healthy controls suggests that rTMS increases coupling of the DLPFC network with another functional brain network involved in reward. Using sophisticated neuroimaging techniques that concurrently capture functional MRI while patients are being stimulated with rTMS, the investigators will identify patterns of brain activity associated with depressed mood and measure the coupling of the DLPFC mood circuit with a reward network prior to an acute course of rTMS. Following baseline imaging, all patients will then undergo an accelerated rTMS protocol over the course of five days, using the pre-treatment imaging to localize the brain region (circuit) targeted by the TMS coil. The investigators will also use questionnaires to assess mood and function before, during and after rTMS treatment. Two comparison groups will be included in this study: 1) patients with depression who have ultra-treatment resistant depression and have been referred for consideration of neurosurgical neuromodulation for depression, and 2) persons with milder treatment resistant depression who are referred to the Harquail Centre for rTMS treatment of depression. This research will help us better understand the mechanisms of how rTMS modulates brain activity, improve TMS targeting in depression, and identify pre-treatment imaging that predict response to rTMS with potentially far-reaching clinical implications.
- Conditions
- Major Depressive Disorder
- Being tested
- rTMS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
Accelerated iTBS treatment
| Study group | Role | What they receive |
|---|---|---|
| Accelerated iTBS treatment | Experimental | accelerated iTBS treatment protocol over 5 consecutive days Receives: Device: rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depressive symptomatology
Change in depression symptomatology as assessed by the clinician-rated 17-item Hamilton Depression Rating Scale (range 0-52)
Measured: 3 years
Imaging
fMRI target engagement in the subgenual anterior cingulate cortex (sgACC)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2023
- Study start27 Sep 2023
- Primary completion7 Jul 2025 (estimated)
- Study completion7 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- We propose a pilot study using state-of-the-art concurrent fMRI acquisition to identify circuits involved with mood, and to subsequently use concurrent interleaved iTBS-fMRI and neuronavigation to examine/dynamically probe, for the first time, how iTBS of the left DLPFC mediates target engagement/functional connectivity between the DLPFC-sgACC circuit and reward system in TRD versus UTRD across varying stimulation amplitude (i.e. doses). Our secondary objective is to identify subtypes of UTRD/TRD patients from pre-treatment iTBS-fMRI who demonstrate clinical improvement in depressive symptoms with a previously validated accelerated iTBS treatment protocol over 5 consecutive days \[6\].
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Sean Michael Nestor, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05813093
- Sponsor's protocol ID
- 5408
- Status last verified
- Nov 2024
- First submitted
- 13 Mar 2023
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Silver D, Vasileiadi M, Menon T, Pople CB, Musa L, Rabin JS, Giacobbe P, Hamani C, Davidson B, Lipsman N, Nestor SM. An exploratory study of glycemic biomarkers and rTMS treatment outcomes in treatment-resistant depression. BMC Psychiatry. 2026 Mar 23;26(1):357. doi: 10.1186/s12888-026-07999-x.
PubMed 41872771
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interleaved TMS-fMRI to Evaluate Intermittent Theta-burst and Dorsolateral Prefrontal Circuit Engagement in Ultra-treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT05813093
- Acronym / sponsor ID
- 5408
- Conditions
- Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 27 Sep 2023 (actual)
- Primary completion
- 7 Jul 2025 (estimated)
- Study completion
- 7 Jul 2025 (estimated)
- First posted
- 14 Apr 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.
This is a study that will recruit patients from the neurosurgery clinic and the regular TMS clinic. It's a smaller study designed to collect brain imaging pre-treatment and then use image guided TMS to treat patient with a one week "accelerated" rTMS protocol using the research TMS machine that is housed in Dr. Sean Nestor's lab. The idea is to examine whether severe treatment resistant depression has a different brain signature than less severe/TRD and whether the investigators can get a therapeutic response from patients that would otherwise undergo neurosurgery or will ultimately undergo neurosurgery.
Detailed description
The objective of this study is to assess plasticity in both whole brain connectivity and a mood/affective circuit involving the dorsolateral prefrontal cortex (DLPFC) in individuals undergoing repetitive transcranial magnetic stimulation (rTMS) for treatment of ultra-treatment resistant depression. Our second aim is to explore how these markers predict response to rTMS. The DLPFC is a brain region known to support mood regulation and has functional brain activity that is altered in depression. Past evidence from healthy controls suggests that rTMS increases coupling of the DLPFC network with another functional brain network involved in reward. Using sophisticated neuroimaging techniques that concurrently capture functional MRI while patients are being stimulated with rTMS, the investigators will identify patterns of brain activity associated with depressed mood and measure the coupling of the DLPFC mood circuit with a reward network prior to an acute course of rTMS. Following baseline imaging, all patients will then undergo an accelerated rTMS protocol over the course of five days, using the pre-treatment imaging to localize the brain region (circuit) targeted by the TMS coil. The investigators will also use questionnaires to assess mood and function before, during and after rTMS treatment. Two comparison groups will be included in this study: 1) patients with depression who have ultra-treatment resistant depression and have been referred for consideration of neurosurgical neuromodulation for depression, and 2) persons with milder treatment resistant depression who are referred to the Harquail Centre for rTMS treatment of depression. This research will help us better understand the mechanisms of how rTMS modulates brain activity, improve TMS targeting in depression, and identify pre-treatment imaging that predict response to rTMS with potentially far-reaching clinical implications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- We propose a pilot study using state-of-the-art concurrent fMRI acquisition to identify circuits involved with mood, and to subsequently use concurrent interleaved iTBS-fMRI and neuronavigation to examine/dynamically probe, for the first time, how iTBS of the left DLPFC mediates target engagement/functional connectivity between the DLPFC-sgACC circuit and reward system in TRD versus UTRD across varying stimulation amplitude (i.e. doses). Our secondary objective is to identify subtypes of UTRD/TRD patients from pre-treatment iTBS-fMRI who demonstrate clinical improvement in depressive symptoms with a previously validated accelerated iTBS treatment protocol over 5 consecutive days [6].
| Arm | Type | Receives |
|---|---|---|
| Accelerated iTBS treatment | Experimental | Device: rTMSaccelerated iTBS treatment protocol over 5 consecutive days |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 20-65
- Have a diagnosis of MDD or persistent depressive disorder and meet criteria for a major depressive episode (moderate-severe) according to the DSM 5.0 with a 17-item Hamilton Rating Scale Score in Depression (HRSD-17) of >=18
- UTRD subjects will also have a duration of depressive symptoms >=5 years, treatment resistance to antidepressants will be defined by Maudsley-staging, failing >6 antidepressants (level 4) and >1 adjunctive antidepressants of adequate dose/duration, failed at >=1 psychotherapy, and no response to >=1 trial of esketamine, IV ketamine, ECT or rTMS
- Milder TRD participants will have failed at least 1 antidepressant medication of adequate dose/duration and never had neuromodulation treatment
Key exclusion criteria (8 listed)
- Contraindications to MRI
- Medical/psychiatric co-morbidities that prevent participation in the study or where depression is not the primary psychiatric symptom of concern
- History of psychosis, pregnancy, substance dependence within the last 6 months
- Active neurological disorder
- History of seizure disorder
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 |
|---|---|---|
| rTMSAccelerated iTBS treatment | Device | Accelerated iTBS treatment |
Primary outcome
Change in depressive symptomatology
Time frame: 3 years
Change in depression symptomatology as assessed by the clinician-rated 17-item Hamilton Depression Rating Scale (range 0-52)
Imaging
Time frame: 3 years
fMRI target engagement in the subgenual anterior cingulate cortex (sgACC)
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 15 Nov 2024.
- Derived from this study: PubMed 41872771Silver D, Vasileiadi M, Menon T, Pople CB, Musa L, Rabin JS, Giacobbe P, Hamani C, Davidson B, Lipsman N, Nestor SM. An exploratory study of glycemic biomarkers and rTMS treatment outcomes in treatment-resistant depression. BMC Psychiatry. 2026 Mar 23;26(1):357. doi: 10.1186/s12888-026-07999-x.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Major Depressive Disorder, run by Sunnybrook Health Sciences 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 4 inclusion and 8 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 15 Nov 2024. 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 Anusha Baskaran, PhD (416-480-6100 ext. 61650, anusha.baskaran@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depressive symptomatology (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT05813093, which also lists 1 linked publication.
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 15 Nov 2024.