NCT01887782

Brief Summary

This trial will compare a novel form of rTMS, intermittent Theta Burst Stimulation to the standard conventional high frequency left sided stimulation protocol. The Left dorsolateral prefrontal cortex will be the site of stimulation in both treatment conditions. The site of stimulation will be targeted using MRI co-registration. The study seeks to determine if the two treatment protocols have similar effectiveness in treating major depression.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
414

participants targeted

Target at P75+ for not_applicable major-depressive-disorder

Timeline
Completed

Started Sep 2013

Typical duration for not_applicable major-depressive-disorder

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

First Submitted

Initial submission to the registry

June 25, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 27, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

January 30, 2017

Status Verified

January 1, 2017

Enrollment Period

2.8 years

First QC Date

June 25, 2013

Last Update Submit

January 26, 2017

Conditions

Major Depressive Disorder

Keywords

depressionmagneticbrain stimulationtreatment-resistant

Outcome Measures

Primary Outcomes (1)

  • HAM-D17 score

    Outcome measure is measured by a change in the HAM-D17 score from baseline to week 4 or 6. A 50% improvement in the score is considered response to rTMS. A final score of \<8 is categorized as remission.

    baseline, after each 5 treatment sessions, and 1, 4, and 12 weeks post-treatment

Study Arms (2)

HFL rTMS

EXPERIMENTAL

High Frequency Left repetitive transcranial magnetic stimulation five days per week for 4 weeks

Device: HFL rTMS

iTBS

ACTIVE COMPARATOR

intermittent Theta Burst Stimulation (iTBS) five days per week for 4 weeks

Device: iTBS

Interventions

HFL rTMSDEVICE

Magventure Cool B70 Coil with either RX100 or RX30 Stimulator

HFL rTMS
iTBSDEVICE

Magventure Cool B70 Coil with either RX100 or RX30 Stimulator

iTBS

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • outpatients
  • voluntary and competent to consent
  • Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single, recurrent
  • between ages 18-65
  • failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2)
  • have a score of ≥ 18 on the HAMD-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 history 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 diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform, 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

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 (8)

  • Kaster TS, Dai Y, Vila-Rodriguez F, Downar J, Daskalakis ZJ, Blumberger DM, Rhee TG. Efficacy of intranasal esketamine versus rTMS for treatment-resistant depression: analysis of individual participant data from two clinical trials. EClinicalMedicine. 2025 Oct 30;90:103609. doi: 10.1016/j.eclinm.2025.103609. eCollection 2025 Dec.

    PMID: 41245530DERIVED

  • 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

  • Trevizol AP, Downar J, Vila-Rodriguez F, Thorpe KE, Daskalakis ZJ, Blumberger DM. Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: An analysis from the randomised non-inferiority THREE-D trial. EClinicalMedicine. 2020 Apr 30;22:100349. doi: 10.1016/j.eclinm.2020.100349. eCollection 2020 May.

    PMID: 32382720DERIVED

  • Ge R, Downar J, Blumberger DM, Daskalakis ZJ, Vila-Rodriguez F. Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up. Brain Stimul. 2020 Jan-Feb;13(1):206-214. doi: 10.1016/j.brs.2019.10.012. Epub 2019 Oct 18.

    PMID: 31668646DERIVED

  • Hsu JH, Downar J, Vila-Rodriguez F, Daskalakis ZJ, Blumberger DM. Impact of prior treatment on remission with intermittent theta burst versus high-frequency repetitive transcranial magnetic stimulation in treatment resistant depression. Brain Stimul. 2019 Nov-Dec;12(6):1553-1555. doi: 10.1016/j.brs.2019.07.011. Epub 2019 Jul 17.

    PMID: 31350213DERIVED

  • Kaster TS, Downar J, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Blumberger DM. Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study. Am J Psychiatry. 2019 May 1;176(5):367-375. doi: 10.1176/appi.ajp.2018.18091096. Epub 2019 Feb 15.

    PMID: 30764649DERIVED

  • Shalbaf R, Brenner C, Pang C, Blumberger DM, Downar J, Daskalakis ZJ, Tham J, Lam RW, Farzan F, Vila-Rodriguez F. Non-linear Entropy Analysis in EEG to Predict Treatment Response to Repetitive Transcranial Magnetic Stimulation in Depression. Front Pharmacol. 2018 Oct 30;9:1188. doi: 10.3389/fphar.2018.01188. eCollection 2018.

    PMID: 30425640DERIVED

  • Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.

    PMID: 29726344DERIVED

MeSH Terms

Conditions

Depressive Disorder, MajorDepression

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersBehavioral SymptomsBehavior

Study Officials

  • Daniel Blumberger, MD, MSc

    Centre for Addiction and Mental Health

    PRINCIPAL INVESTIGATOR

  • Jonathan Downar, MD, PhD

    University Health Network, Toronto Western Hospital

    PRINCIPAL INVESTIGATOR

  • Fidel Vila-Rodriguez, MD

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Head, Temerty Centre for Therapeutic Brain Intervention

Study Record Dates

First Submitted

June 25, 2013

First Posted

June 27, 2013

Study Start

September 1, 2013

Primary Completion

July 1, 2016

Study Completion

October 1, 2016

Last Updated

January 30, 2017

Record last verified: 2017-01

Locations

CA(3)