Repetitive Versus Deep Transcranial Magnetic Stimulation for Major Depression (ReDeeMD)

Comparative Effectiveness of Repetitive Versus Deep Transcranial Magnetic Stimulation for Major Depression: A Randomized Controlled Trial

The goal of this randomized controlled trial is to he effectiveness of two different TMS techniques in TRD, repetitive TMS (rTMS) and deep TMS (dTMS). The main questions it aims to answer are:

type of study: clinical trial participant population/health conditions : Major Depressive Disorder To assess the superiority of dTMS over rTMS in TRD To evaluate the predictive capacity of scalable candidate biomarkers Participants will be randomly allocated to one of the two intervention groups (rTMS or dTMS).

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: transcranial magnetic stimulation

Detailed Description

The primary aim of this trial is to compare the effectiveness of two different TMS techniques in TRD, repetitive TMS (rTMS) and deep TMS (dTMS). Compared to rTMS, dTMS delivers a broader magnetic field, which in turn reduces coil positioning error and maximizes the probability of optimal cortical stimulation. A past RCT comparing both approaches found a greater depression score decrease and response/remission rates for dTMS, but was short of reaching significance for remission rates (primary outcome). Critical components of this RCT were suboptimal, including too few treatment sessions and insufficient statistical power, both of which could have obscured an actual difference between modalities. Proof of a more effective type of TMS over another would translate into increased odds of improvement for TRD patients who live with a chronic and disabling illness.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Philippe Miron, MD PhD; Phone Number: 26489 514-890-8000; Email: jean-philippe.miron@umontreal.ca
• Study Contact Backup: Name: Véronique Desbeaumes Jodoin, PhD; Phone Number: 26489 514-890-8000; Email: vdesbeaumes@gmail.com

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2X 0C1
      • Recruiting
      • CHUM
      • Contact: Véronique Desbeaumes, Ph.D.
      • Contact: Sylvie Tieu, B.Sc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of Major Depressive Disorder, at least moderate intensity, single or recurrent episode
• HRSD-17 score of at least 18
• No improvement to at least two adequate courses of antidepressants (based on the ATHF) or were unable to tolerate at least two separate trials of antidepressants of inadequate dose and duration
• On a stable antidepressant regimen for the past four weeks before screening
• Patients with a chronic depressive episode >2 years and who have previously received ECT or ketamine will be eligible to participate

Exclusion Criteria:

• Having previously received TMS;
• Substance use disorder within the last three months
• Diagnosis of bipolar or psychosis spectrum disorder
• Anxiety or personality disorder that is assessed by a study investigator to be the primary cause and causing greater impairment than MDD
• Concomitant major unstable medical or neurological illness
• Intracranial implant, cardiac pacemaker or implanted medication pump
• Significant laboratory abnormality;
• Active suicidal intent
• Pregnancy
• If participating in psychotherapy, must have been in stable treatment for at least three months before entry into the study, with no anticipation of change
• Currently taking more than the equivalent of 2 mg of lorazepam of a benzodiazepine daily or any dose of an anticonvulsant due to the potential to limit TMS effectiveness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: repetitive Transcranial Magnetic Stimulation; rTMS on a MagPro X100 research grade stimulator (MagVenture) equipped with a B70 fluid-cooled coil. Participant will receive the MDD FDA-approved iTBS protocol (triplet 50 Hz bursts repeated at 5 Hz, 2 s ON and 8 s OFF; 600 pulses per session; total duration of 3 min 9 s, 120% hand motor threshold)	Device: transcranial magnetic stimulation; Participants will receive either rTMS or dTMS; Other Names: deep transcranial magnetic stimulation
Experimental: deep Transcranial Magnetic Stimulation; dTMS on a research Brainsway system equipped with an H7-Coil. Participants will receive the MDD FDA-cleared 18 Hz stimulation protocol (2 sec ON, 20 sec OFF, 55 trains; 1980 pulses per session; 20 min 10 s duration; 120% hand motor threshold)	Device: transcranial magnetic stimulation; Participants will receive either rTMS or dTMS; Other Names: deep transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Rating Scale for Depression-17 (HRSD-17)	score change. Higher score means worse outcome. (Min = 0, Max = 53)	Baseline to Week 6
Response (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score reduction of 50% or more	baseline to Week 6
Remission (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score of 7 or less	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Rating Scale for Depression-17	score change. Higher score means worse outcome. (Min = 0, Max = 53)	Baseline to Week 7
Hamilton Rating Scale for Depression-17	score change. Higher score means worse outcome. (Min = 0, Max = 53)	Baseline to Week 10
Hamilton Rating Scale for Depression-17	score change. Higher score means worse outcome. (Min = 0, Max = 53)	Baseline to Week 18
Response (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score reduction of 50% or more	Baseline to Week 7
Response (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score reduction of 50% or more	Baseline to Week 10
Response (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score reduction of 50% or more	Baseline to Week 18
Remission (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score of 7 or less	Baseline to Week 7
Remission (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score of 7 or less	Baseline to Week 10
Remission (yes/no) on Hamilton Rating Scale for Depression-17	Defined as a score of 7 or less	Baseline to Week 18
Hamilton Rating Scale for Depression-28	score change. Higher score means worse outcome. (Min = 0, Max = 90)	Baseline to Week 6, Week 7, Week 10, Week 18
Hamilton Anxiety Rating Scale (HAM-A)	score change. Higher score means worse outcome. (Min = 0, Max = 56)	Baseline to Week 6, Week 7, Week 10, Week 18
Quick Inventory of Depressive Symptomatology (self-report) (QIDS-SR 16)	score change. Higher score means worse outcome. (Min = 0, Max = 42)	Baseline to Week 6, Week 7, Week 10, Week 18
General Anxiety Disorder-7 (GAD-7)	score change. Higher score means worse outcome. (Min = 0, Max = 21)	Baseline to Week 6, Week 7, Week 10, Week 18
Snaith-Hamilton Pleasure Scale (SHAPS)	score change. Higher score means worse outcome. (Min= 0, Max = 56)	Baseline to Week 6, Week 7, Week 10, Week 18
Columbia-Suicide Severity Rating Scale (C-SSRS)	score change. Higher score means worse outcome. (Min = 0, Max = 30)	Baseline to Week 6, Week 7, Week 10, Week 18
Rumination Response Scale (RRS)	score change. Higher score means worse outcome. (Min = 0, Max = 88)	Baseline to Week 6, Week 7, Week 10, Week 18
Adult AHDH Self-Report Scale	qualitative.	Baseline to Week 18
McLean Screening Instrument for Borderline Personality Disorder	score. Higher score means worse outcome. (Min = 0, Max = 10)	Baseline
World Health Organization Quality of Life Short Version (WHOQOL-BREF)	Difference score. Lower score means worse outcome. (Min = 26, Max = 130)	Baseline to Week 6, Week 7, Week 10, Week 18
Cognitive Difficulties Scale (MacNair-R)	Difference score. Higher score means worse outcome. (Min = 0, Max = 156)	Baseline to Week 6, Week 7, Week 10, Week 18
Memory Complaints Scale (MacNair)	score. Higher score means worse outcome. (Min = 0, Max = 45)	Baseline to Week 6, Week 7, Week 10, Week 18
Visual Pain Scale	Maximum score (during treatment). Higher score means worse outcome. (Min = 0, Max = 10).	Each treatment day
Sex and Gender scale	Descriptive statistics	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electroencephalogram to predict treatment response	individual alpha frequency	Baseline
Electroencephalogram event-related potentials	Reward positivity	Baseline
Electrocardiogram	corrected QT interval	Baseline
Pupil measures	pupil reactivity measures	Baseline

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Jean-Philippe Miron, MD PhD, Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Publications and helpful links

Helpful Links

• research website

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: June 12, 2023
• First Posted (Actual): June 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MDD; TMS; deep TMS
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 2023-11389

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