Interleaved TMS-fMRI in Ultra-treatment Resistant Depression

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

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: rTMS

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, 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.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anusha Baskaran, PhD; Phone Number: 61650 416-480-6100; Email: anusha.baskaran@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: aNUSHA Basakran, PhD; Phone Number: 61650 416-480-6100; Email: anusha.baskaran@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated iTBS treatment; accelerated iTBS treatment protocol over 5 consecutive days	Device: rTMS; Accelerated iTBS treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging	fMRI circuits involved with mood	3 years

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2023
• Primary Completion (Estimated): July 7, 2025
• Study Completion (Estimated): July 7, 2025

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 5408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No