Accelerated Neuromodulation of Anterior Cingulate Cortex for Depression

NCT07212465 | Recruiting FDA Device

• 1 other identifier: 25-03
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test whether an accelerated deep Transcranial Magnetic Stimulation (dTMS) protocol can reduce depressive symptoms in older adults (ages 60-85) with Major Depressive Disorder (MDD) who have not tolerated or responded to antidepressant medications. The study will evaluate whether accelerated dTMS administered over 5 consecutive days is safe and well-tolerated in this population, and whether it produces greater reductions in depressive symptoms compared to placebo stimulation.

Conditions

Major Depressive Disorder (MDD)

Keywords

Transcranial Magnetic Stimulation (TMS); Treatment Resistant Depression; Intermittent Theta Burst Stimulation

Outcome Measures

Primary Outcomes (4)

• Percentage of scheduled treatment sessions that are attended by study participants

  6 weeks

• Participant-reported comfort and feasibility based on the frequency and type of adverse events as measured using the Adverse Events Questionnaire (AEQ)

  Severity of symptoms is rated from 1 to 4, with 1 being absent and 4 being severe. Whether symptoms are perceived to be relatedTMS treatment are rated from 1 to 5, with 1 being no and 5 being definitely.

  6 weeks

• The number of participants who have prematurely withdraw and reasons for withdrawal

  6 weeks

• The change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores following the final treatment on day 5 (i.e., after 5 days of H7-coil a-iTBS) in the treatment group compared to the sham group.

  An effect size (Cohen's d) of 0.5 will be considered a minimally important effective size. The MADRS ranges from 0-60, with a greater score indicating greater depressive symptoms.

  1 week

Secondary Outcomes (8)

• Response rates compared between treatment groups following 5 days of treatment, where the response rate refers to the percentage of patients who responded to a-ITBS treatment and response is defined as a ≥50% reduction in MADRS score from baseline

  6 weeks

• Remission rates compared between treatment groups following 5 days of treatment, where the remission rate is defined as MADRS score <10

  6 weeks

• The change in baseline slow wave and resting state activity as measured with electroencephalography (EEG) following 5 days of treatment and at 1-month follow-up

  6 weeks

• The change in functional connectivity within the default mode and central autonomic networks on Magnetic Resonance Imaging (MRI)

  1 week

• The change in slow wave activity in the posterior default mode network (posterior cingulate cortex) as measured with MEG

  1 week

Study Arms (2)

20-40 sessions of sham stimulation

SHAM COMPARATOR

Participants will receive sham intervention if randomized into sham condition. The sham intervention consists of treatment with similar technical parameters which induce scalp sensations but do not penetrate into the brain.

Device: Sham Brainsway H1-Coil Deep TMS System

20-40 sessions of iTBS dTMS

EXPERIMENTAL

Participants will receive dTMS if randomized into the active condition. The motor threshold (MT) will be measured by delivering single stimulations to the motor cortex with gradually increased intensity. The stimulation protocol consists of 6-8 dTMS sessions of intermittent theta burst stimulation delivered at an intensity of 80-90% of resting MT each day for five consecutive days

Device: Active Brainsway H7-Coil Deep TMS System

Interventions

Active Brainsway H7-Coil Deep TMS System DEVICE

Deep Transcranial Magnetic Stimulation (dTMS) is a new form of TMS which allows direct stimulation of deeper neuronal pathways than the standard TMS. The H-coil is a novel dTMS coil designed to allow deeper brain stimulation without a significant increase of electric fields induced in superficial cortical regions. dTMS will be administered 6-8 times a day for 5 consecutive days.

20-40 sessions of iTBS dTMS

Sham Brainsway H1-Coil Deep TMS System DEVICE

In addition to the active H7-coil, a sham coil is included in the H1-coil helmet. The sham treatment will be administered 6-8 times a day for 5 consecutive days.

20-40 sessions of sham stimulation

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• are between 60- 85 years old (on the day of randomization)
• have been diagnosed with DSM5 Major Depressive Disorder, with the current episode longer than 4 weeks but less than 5 years
• did not respond to/did not tolerate, or failed to achieve remission with at least one antidepressant trial of 8 week minimum duration
• are willing to provide informed consent
• are able to follow the treatment schedule
• are stable on medications for 2 months and are not expected to change medication during the entire study period (if they are taking medications)
• have a satisfactory safety screening questionnaire for TMS

You may not qualify if:

• have a metal plate in your head (such as an ear implant, implanted brain stimulators, aneurysm clips). Dental devices and implants that are non-magnetic are safe
• have known increased pressure or a history of increased pressure in their brain, which may increase their risk for having seizures
• have a cardiac pacemaker
• have an implanted medication pump
• have a central venous line
• have a history of any psychotic disorder, bipolar disorder, eating disorder, obsessive compulsive disorder, post-traumatic stress disorder, or dementia
• have a history of substance abuse in the last 6 months
• have a history of stroke or other brain lesions
• have a personal history of epilepsy
• have a family history of epilepsy
• are a pregnant or breast-feeding woman
• have a history of abnormal MRI of the brain
• have untreated hypo- or hyper-thyroidism
• have unstable medical condition(s)
• have any other known contraindications to TMS

Sponsors & Collaborators

• Rotman Research Institute at Baycrest: lead

Study Sites (1)

Rotman Research Institute at Baycrest

Toronto, Ontario, M6A 2E1, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Linda Mah, MD

  Baycrest Rotman Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda Chao, MPH

CONTACT

416-785-2500; preventad@research.baycrest.org

Linda Mah, MD

CONTACT

416-785-2500; preventad@research.baycrest.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: October 8, 2025
• Study Start: July 21, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 15, 2027
• Last Updated: October 28, 2025

Record last verified: 2025-09

Locations

CA (1)