NCT02729792

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for medically refractory major depressive disorder (MDD). rTMS involves direct stimulation of cortical neurons using externally applied, powerful, focused magnetic field pulses. Dozens of studies and several meta-analyses over the last 15 years have shown that rTMS of the dorsolateral prefrontal cortex (DLPFC) produces statistically significant improvements in MDD, even when medications have failed. However, other possible targets may also yield improvement in symptoms. In an attempt to enhance the therapeutic efficacy of current interventions for TRD, attention has turned to identifying domain-specific biomarkers in hopes of ultimately individualizing and predicting treatment response. Unfortunately, the precise nature of this relationship is less than clear, as reflected by the fact that even now there are no established biomarkers that are used routinely in clinical practice to aid in diagnosis. This study also seeks to examine a comprehensive suite of biomarker measurements (MRI, neurophysiology, and genomics/proteomics) before and after rTMS treatment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
212

participants targeted

Target at P75+ for not_applicable depression

Timeline
Completed

Started Mar 2016

Typical duration for not_applicable depression

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2016

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

March 29, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 6, 2016

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2018

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2018

Completed
Last Updated

July 26, 2018

Status Verified

July 1, 2018

Enrollment Period

2 years

First QC Date

March 29, 2016

Last Update Submit

July 24, 2018

Conditions

Depression

Keywords

depressiontreatment resistancebiomarkersrepetitive transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

  • 17-item Hamilton Rating Scale for Depression (HRSD-17) Change

    Change from baseline to 10 days

    10 days

Secondary Outcomes (1)

  • 17-item Hamilton Rating Scale for Depression (HRSD-17) Change

    30 days

Other Outcomes (8)

  • Beck Depression Inventory-II Change

    10 days

  • Quick Inventory of Depressive Symptoms Change

    10 days

  • 17-item Hamilton Rating Scale for Depression (HRSD-17) Remission

    10 days

  • +5 more other outcomes

Study Arms (2)

Single site rTMS

EXPERIMENTAL

Each treatment session will consist of: 1200 pulses of iTBS over a posterior target location followed by a 60 minute interval, then 1200 pulses of iTBS over an anterior target location.

Device: rTMS

Dual site rTMS

ACTIVE COMPARATOR

Each treatment session will consist of: 600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location followed by a 60 minute interval, then 600 pulses of iTBS over the posterior target, followed immediately by 600 pulses of iTBS over the anterior target location.

Device: rTMS

Interventions

rTMSDEVICE

intermittent theta burst stimulation (iTBS)

Dual site rTMSSingle site rTMS

Eligibility Criteria

Age18 Years - 59 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • are outpatients
  • are voluntary and competent to consent to treatment
  • have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent
  • are between the ages of 18 and 59
  • have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 3 in the current episode 105,106 OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants)
  • have a score \> 18 on the HRSD-17 item
  • have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
  • able to adhere to the treatment schedule
  • Pass the TMS adult safety screening (TASS) questionnaire
  • have normal thyroid functioning based on pre-study blood work.

You may not qualify if:

  • have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months
  • have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
  • have active suicidal intent
  • are pregnant
  • have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms
  • have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
  • have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
  • have failed a course of ECT in the current episode or previous episode
  • have received rTMS for any previous indication due to the potential compromise of subject blinding
  • have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes
  • have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
  • if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
  • clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians
  • currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy
  • non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Non-Invasive Neurostimulation Therapies Centre, University of British Columbia

Vancouver, British Columbia, V6T 2A1, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related Publications (4)

  • Chen X, Blumberger DM, Yan CG, Downar J, Vila-Rodriguez F, Daskalakis ZJ, Kaster TS. Crosswalk between HRSD and MADRS outcomes for rTMS in patients with depression. BMJ Ment Health. 2025 Mar 28;28(1):e301451. doi: 10.1136/bmjment-2024-301451.

    PMID: 40154967DERIVED

  • Zapf L, Kaster TS, Vila-Rodriguez F, Daskalakis ZJ, Downar J, Blumberger DM. The effect of once-daily vs. twice-daily intermittent theta burst stimulation on suicidal ideation in treatment-resistant depression. Eur Arch Psychiatry Clin Neurosci. 2025 Sep;275(6):1787-1798. doi: 10.1007/s00406-024-01929-2. Epub 2024 Nov 15.

    PMID: 39545967DERIVED

  • Kaster TS, Downar J, Vila-Rodriguez F, Baribeau DA, Thorpe KE, Daskalakis ZJ, Blumberger DM. Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depression. EClinicalMedicine. 2022 Dec 2;55:101765. doi: 10.1016/j.eclinm.2022.101765. eCollection 2023 Jan.

    PMID: 36483268DERIVED

  • Blumberger DM, Vila-Rodriguez F, Wang W, Knyahnytska Y, Butterfield M, Noda Y, Yariv S, Isserles M, Voineskos D, Ainsworth NJ, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Brain Stimul. 2021 Nov-Dec;14(6):1447-1455. doi: 10.1016/j.brs.2021.09.003. Epub 2021 Sep 21.

    PMID: 34560319DERIVED

Related Links

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehavior

Study Officials

  • Daniel M. Blumberger, MD, MSc

    CAMH

    PRINCIPAL INVESTIGATOR

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
Medical Head and Co-Director, Temerty Centre for Therapeutic Brain Intervention

Study Record Dates

First Submitted

March 29, 2016

First Posted

April 6, 2016

Study Start

March 1, 2016

Primary Completion

February 23, 2018

Study Completion

May 30, 2018

Last Updated

July 26, 2018

Record last verified: 2018-07

Locations

CA(3)