Interleaved TMS-fMRI in Ultra-treatment Resistant Depression

Major Depressive Disorder Clinical Trial

Official title:

Interleaved TMS-fMRI to Evaluate Intermittent Theta-burst and Dorsolateral Prefrontal Circuit Engagement in Ultra-treatment Resistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05813093
• Other study ID #: 5408
• Status: Recruiting
• Phase: N/A
• Start date: September 27, 2023
• Est. completion date: July 7, 2025

Study information

• Verified date: October 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Anusha Baskaran, PhD
• Phone: 416-480-6100
• Email: anusha.baskaran[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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 we can get a therapeutic response from patients that would otherwise undergo neurosurgery or will ultimately undergo neurosurgery.

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, we 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. We 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/EEG markers that predict response to rTMS with potentially far-reaching clinical implications.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: July 7, 2025
• Est. primary completion date: July 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion criteria:

• 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

Exclusion criteria:

• 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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder

Intervention

Device:
• rTMS
Accelerated iTBS treatment

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Imaging	fMRI circuits involved with mood	3 years