Interleaved TMS-fMRI in Ultra-treatment Resistant Depression

NCT05813093 | Recruiting

• 1 other identifier: 5408
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• Change in depressive symptomatology

  Change in depression symptomatology as assessed by the clinician-rated 17-item Hamilton Depression Rating Scale (range 0-52)

  3 years

• Imaging

  fMRI target engagement in the subgenual anterior cingulate cortex (sgACC)

  3 years

Other Outcomes (1)

• Predictive capacity of fMRI target engagement

  3 years

Study Arms (1)

Accelerated iTBS treatment

EXPERIMENTAL

accelerated iTBS treatment protocol over 5 consecutive days

Device: rTMS

Interventions

rTMS DEVICE

Accelerated iTBS treatment

Accelerated iTBS treatment

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Anusha Baskaran, PhD

CONTACT

416-480-6100; anusha.baskaran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Investigator

Model Details: 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 \[6\].

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 14, 2023
• Study Start: September 27, 2023
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)