NCT01515215

Brief Summary

Major Depressive Disorder (MDD) is one of the most prevalent mental illnesses in North America, in which 30% - 40% fail to respond to conventional treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to be an effective therapeutic tool for the treatment of MDD. This form of treatment involves a series of magnetic pulses directed to the brain for about 30 minutes. Importantly, such treatment is very safe and well tolerated. However, to date, most treatment studies show modest efficacy due to limitations, including: 1) treatments that are delivered to only one side of the brain; 2) treatment that does not directly target a specific brain region associated with depression; 3) treatments that are of short duration; 4) treatments that are of insufficient intensity; and 5) insufficient understanding of the brain mechanisms responsible for therapeutic effect. This study is designed to directly address all of these limitations, as well as explore brain mechanisms (e.g. cortical excitability) through which treatment is optimized.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
107

participants targeted

Target at P50-P75 for not_applicable major-depressive-disorder

Timeline
Completed

Started Jul 2008

Longer than P75 for not_applicable major-depressive-disorder

Geographic Reach
1 country

1 active site

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

July 1, 2008

Completed
3.6 years until next milestone

First Submitted

Initial submission to the registry

January 18, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 24, 2012

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

November 1, 2016

Status Verified

October 1, 2016

Enrollment Period

8.3 years

First QC Date

January 18, 2012

Last Update Submit

October 31, 2016

Conditions

Major Depressive Disorder

Keywords

Major Depression DisorderTreatment Resistancerepetitive Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

  • Degree of Change in HAM-D17 Scores

    At weeks 3 and/or 6

Secondary Outcomes (4)

  • Degree of Change in Montgomery-Asberg Depression Rating Scale Scores

    At weeks 3 and/or 6

  • Degree of Change in Beck Depression Inventory Scores

    At weeks 3 and/or 6

  • Degree of Change in Brief Psychiatric Ratings Scale Scores

    At weeks 3 and/or 6

  • Changes in Cortical Excitability

    At weeks 3 and/or 6

Study Arms (3)

High-frequency Left rTMS

ACTIVE COMPARATOR

Intensity: rTMS treatment intensity determined by using resting motor threshold (RMT). Treatment will be delivered at 120% of the RMT. Site of Stimulation: left hemisphere of DLPFC. Frequency: 10 Hz. Duration: 42 Trains, 5 second duration, 25 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation

Bilateral rTMS

ACTIVE COMPARATOR

Intensity: rTMS treatment intensity determined by the RMT. Treatment will be delivered at 120% of the RMT. Sites of Stimulation: right and left hemispheres of the DLPFC. Frequency: 1 Hz over the right DLPFC followed by 10 Hz over the left DLPFC. Duration: right: 1 Train of 600 pulses; left: 30 Trains, 5 second duration, 25 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation

Sham rTMS

SHAM COMPARATOR

Sham rTMS Treatment is applied as either Bilateral rTMS or HFL-rTMS (randomly assigned), but with the coil angled 90 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic StimulationDEVICE

Magnetic pulses to specific brain regions. (MagPro X100)

Also known as: MagPro X100 Series (Magventure A/S, Farum, Denmark)
Bilateral rTMSHigh-frequency Left rTMSSham rTMS

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • voluntary and competent to consent
  • diagnosis of MDD, as confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV)
  • years of age
  • failed to achieve clinical response, or did not tolerate, at least 2 separate antidepressant trials of sufficient dosage for at least 6 wks
  • have a score of 20 or greater on the HAM-D17
  • have not had an increase or initiation of any psychoactive therapy in the 4 wks prior to testing
  • if a woman of childbearing potential, must be on an effective means of birth control

You may not qualify if:

  • history of DSM-IV confirmed diagnosis of substance dependence in the last 6 months, or substance abuse in the last month
  • concomitant, major, unstable medical or neurologic illness
  • history of seizures
  • acutely suicidal and/or homicidal
  • pregnant
  • have metal implants
  • history of psychosurgery
  • co-morbid diagnosis of borderline and/or antisocial personality disorder. as confirmed by the SCID for Axis II Disorders (SCID-II)
  • are currently (or in the past 4 weeks) taking more than 2 mg of lorazepam, or equivalent, daily
  • ECT treatment in the current episode

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related Publications (4)

  • Hadas I, Sun Y, Lioumis P, Zomorrodi R, Jones B, Voineskos D, Downar J, Fitzgerald PB, Blumberger DM, Daskalakis ZJ. Association of Repetitive Transcranial Magnetic Stimulation Treatment With Subgenual Cingulate Hyperactivity in Patients With Major Depressive Disorder: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2019 Jun 5;2(6):e195578. doi: 10.1001/jamanetworkopen.2019.5578.

    PMID: 31167023DERIVED

  • Trevizol AP, Goldberger KW, Mulsant BH, Rajji TK, Downar J, Daskalakis ZJ, Blumberger DM. Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant late-life depression. Int J Geriatr Psychiatry. 2019 Jun;34(6):822-827. doi: 10.1002/gps.5091. Epub 2019 Apr 8.

    PMID: 30854751DERIVED

  • Voineskos D, Blumberger DM, Zomorrodi R, Rogasch NC, Farzan F, Foussias G, Rajji TK, Daskalakis ZJ. Altered Transcranial Magnetic Stimulation-Electroencephalographic Markers of Inhibition and Excitation in the Dorsolateral Prefrontal Cortex in Major Depressive Disorder. Biol Psychiatry. 2019 Mar 15;85(6):477-486. doi: 10.1016/j.biopsych.2018.09.032. Epub 2018 Oct 18.

    PMID: 30503506DERIVED

  • Weissman CR, Blumberger DM, Brown PE, Isserles M, Rajji TK, Downar J, Mulsant BH, Fitzgerald PB, Daskalakis ZJ. Bilateral Repetitive Transcranial Magnetic Stimulation Decreases Suicidal Ideation in Depression. J Clin Psychiatry. 2018 May/Jun;79(3):17m11692. doi: 10.4088/JCP.17m11692.

    PMID: 29701939DERIVED

Related Links

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Z. Jeffrey Daskalakis, MD, PhD.

    Centre for Addiction and Mental Health

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

January 18, 2012

First Posted

January 24, 2012

Study Start

July 1, 2008

Primary Completion

October 1, 2016

Study Completion

October 1, 2016

Last Updated

November 1, 2016

Record last verified: 2016-10

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)