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

• ClinicalTrials.gov Identifier: NCT05902312
• Recruitment Status: Recruiting
• First Posted: June 13, 2023
• Last Update Posted: April 18, 2024
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information

• First Submitted Date: May 31, 2023
• First Posted Date: June 13, 2023
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: January 1, 2024
• Estimated Primary Completion Date: January 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2023)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 16, 2024)

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

Original Secondary Outcome Measures (submitted: June 12, 2023)

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

Current Other Pre-specified Outcome Measures (submitted: October 26, 2023)

• Electroencephalogram to predict treatment response [ Time Frame: Baseline ]
  individual alpha frequency
• Electroencephalogram event-related potentials [ Time Frame: Baseline ]
  Reward positivity
• Electrocardiogram [ Time Frame: Baseline ]
  corrected QT interval
• Pupil measures [ Time Frame: Baseline ]
  pupil reactivity measures

Original Other Pre-specified Outcome Measures (submitted: June 12, 2023)

• Electroencephalogram to predict treatment response [ Time Frame: Baseline ]
  individual alpha frequency
• Electroencephalogram event-related potentials [ Time Frame: Baseline ]
  Reward positivity
• Electrocardiogram [ Time Frame: Baseline ]
  corrected QT interval
• Neuro Cardiac Guided TMS [ Time Frame: Baseline ]
  measure of heart rate deceleration to treatment

Descriptive Information

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

Brief Summary

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).

• 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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

randomized, single-center, two-arm, parallel-group superiority trial

Masking: Single (Outcomes Assessor)
Masking Description:

Given the study's design, blinding participants and TMS operators will not be possible. Still, staff responsible for participant assessments and data analysis will be blinded to treatment conditions and external to the clinic staff. Patients will be instructed not to reveal their group assignment to the raters. Patients will not be given the specifics of the treatment parameters and will be instructed not to talk to each other during the study period. Both treatments will be presented as effective to them. Lastly, the data management center will strictly control access to the randomization code.

Primary Purpose: Treatment

• Condition: Major Depressive Disorder

Intervention

Device: transcranial magnetic stimulation

Participants will receive either rTMS or dTMS

Other Name: deep transcranial magnetic stimulation

Study Arms

• 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)
  Intervention: Device: 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)
  Intervention: Device: transcranial magnetic stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 28, 2023): 50
• Original Estimated Enrollment (submitted: June 12, 2023): 220
• Estimated Study Completion Date: September 1, 2027
• Estimated Primary Completion Date: January 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jean-Philippe Miron, MD PhD; 514-890-8000 ext 26489; jean-philippe.miron@umontreal.ca

Contact: Véronique Desbeaumes Jodoin, PhD; 514-890-8000 ext 26489; vdesbeaumes@gmail.com

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05902312
• Other Study ID Numbers: 2023-11389
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Original Study Sponsor: Same as current
• 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

• PRS Account: Centre hospitalier de l'Université de Montréal (CHUM)
• Verification Date: April 2024