Neural Mechanisms of Intermittent Theta Burst Stimulation in the Core Depression Network

NCT05224206 | Recruiting

• 1 other identifier: 2021013
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Repetitive Transcranial magnetic stimulation (TMS) uses magnetic fields to modulate brain activity. A novel form of repetitive TMS (rTMS), intermittent theta burst stimulation (iTBS), has emerged as a promising new treatment for depression. This technique may be advantageous due to its very short duration and potentially stronger effect on brain activity in comparison with standard rTMS. However, the exact effect of iTBS on the activity of the brain in clinical populations remains poorly understood. This project aims to improve understanding of the mechanisms of action of iTBS by comparing its neuronal effect to sham treatment in 22 individuals with a diagnosis of major depressive episode, using positron emission tomography (PET) and magnetic resonance imaging (MRI) in a double-blind cross-over experiment, followed by a 6-week daily treatment course of iTBS.

Conditions

Major Depressive Disorder

Keywords

iTBS; rTMS; positron emission tomography

Outcome Measures

Primary Outcomes (2)

• Neural mechanisms of iTBS measured by [18F]FDG uptake in the sgACC

  The primary outcome measure for Part I is the change in \[18F\]FDG uptake in the sgACC after iTBS.

  40 minutes after iTBS

• Neuroimaging predictors of iTBS response to treatment - primary measures

  The primary clinical outcome measures will be response to treatment and remission. Response to treatment will be defined as at least a 50% reduction in pre-treatment symptoms severity as measured by the mean HRSD-17 score at week 6. Remission will be defined as a HRSD-17 score lower or equal to 7 at week 6.

  6 weeks

Secondary Outcomes (4)

• Neuroimaging predictors of iTBS response to treatment - QIDS-SR16

  6 weeks

• Neuroimaging predictors of iTBS response to treatment - Beck Anxiety Inventory (BAI)

  6 week

• Neuroimaging predictors of iTBS response to treatment - Quality of life (Q-LES-Q-SF)

  6 week

• Neuroimaging predictors of iTBS response to treatment - Well-being (WEMWBS)

  6 week

Study Arms (2)

Sham iTBS/Active iTBS

SHAM COMPARATOR

Intermittent Theta Burst Stimulation (iTBS) or realistic sham iTBS will be applied to the left DLPFC. Both sessions will be one week apart.

Device: Theta burst stimulation

Active iTBS

ACTIVE COMPARATOR

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left DLPFC. Participants will receive daily sessions (on weekdays) for 6 weeks.

Device: Theta burst stimulation

Interventions

Theta burst stimulation DEVICE

Cool B65 active/placebo coil (left DLPFC) with X100 MagPro rTMS Device (Magventure A/S, Farum, Denmark)

Sham iTBS/Active iTBS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men or women aged 18 to 55 years of age
• Mini-International Neuropsychiatric Interview-confirmed diagnosis of MDD, as a single or recurring episode
• Symptoms of MDD have not improved after ≥ 1 but ≤ 7 adequate dose(s) of antidepressant trial(s) in the current depressive episode
• A baseline score of ≥ 15 on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
• Have received a stable antidepressant regimen for at least four weeks prior to entering trial
• Are voluntary and competent to consent to study
• Can speak and read English

You may not qualify if:

• Current or past (\< 3 months) substance (including nicotine) or alcohol abuse/dependence, as defined in DSM-5 criteria
• Positive urine test for illegal substances, cannabis, or cotinine
• Suicide attempt in the past three months and/or active suicidal intent
• Pregnancy (confirmed by urine test) and/or lactation
• Psychotic features in the current episode
• Any comorbid mental health disorders (including, but not limited to lifetime history of psychotic disorders, OCD, PTSD and/or bipolar I or II disorder) with the exception of anxiety/panic disorders and ADHD
• Significant unstable medical or neurologic illness confirmed by medical history and blood test at baseline (e.g. uncontrolled diabetes, or renal dysfunction)
• Organic cause to the depressive symptoms (e.g. thyroid dysfunctions), as ruled out by the referring physician
• Contraindication for TMS (e.g., personal history of epilepsy or convulsion, metallic head implant, pacemaker)
• Contraindication for MRI (e.g. metallic implant, claustrophobia)
• Have undergone a prior PET or SPECT research study
• ECT or rTMS treatment in the current depressive episode
• Benzodiazepine use
• Have a body mass index (BMI) higher then 35 or lower then 18
• Any other condition that, in the opinion of the investigators, would adversely affect the participant's ability to complete the study

Sponsors & Collaborators

• The Royal Ottawa Mental Health Centre: lead

Study Sites (1)

The Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Sara Tremblay, PhD

  The Royal Ottawa Mental Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey Shim, MSc

CONTACT

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

Jessica Drodge, MSc

CONTACT

613-722-6521; jessica.drodge@theroyal.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study will be divided in two main parts. In Part I, we will use a randomized cross-over double-blinded design. The order of the iTBS conditions (active vs. sham) will be counterbalanced across participants. In part II, participants will receive a 6-week daily iTBS open-label treatment. Participants and research team members performing iTBS and analyses will be blind to the stimulation condition for Part I of the study. The order of the conditions will be determined by a separate research team member that will not be performing iTBS or analyses. Participants will be told that there is a sham condition, for Part I of the trial. The master randomization list was created by a scientist of the research centre that is not involved in the research project.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: February 4, 2022
• Study Start: April 26, 2023
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: De-identified data may become available (upon request) when the study is completed and published (anticipated time frame: the year of 2024)
• Access Criteria: De-identified data will be accessible only through the permission of the lead research scientist. All requests must be made and accepted by her.

Locations

CA (1)