NCT01409317

Brief Summary

Standard high frequency repetitive transcranial magnetic stimulation (HF-TMS) is a noninvasive method to activate or de-activate neurons in superficial regions of the brain through the induction of weak electric currents in the brain tissue produced by rapidly changing magnetic fields. Studies have generally shown standard HF-TMS to be effective in treating major depressive disorder (MDD), although treatment effects are often highly variable and there are several negative trials in the specialized literature. One reason for these discrepant results might be that standard HF-TMS only enables direct stimulation of superficial brain areas and, consequently, it is possible that the stimulation of deeper and more widespread brain regions could produce superior and more reliable results. Recently, a novel form of HF-rTMS (called deep transcranial magnetic stimulation or DTMS), that allows direct stimulation of much larger and deeper brain regions, has also been shown to be effective and safe in treating MDD. Neuroimaging studies have shown that standard HF-rTMS directly affects several superficial areas of the brain, but to date there is no data on the brain effects of DTMS. Thus, this study aims to explore, for the first time, the brain effects of DTMS in MDD. More specifically, we, the investigators, hope to identify possible neural predictors of clinical improvement after DTMS and also clarify the impact of DTMS in the brain activity over time. In this study, DTMS will be applied over the left side of the front of the head (a region known as the 'prefrontal cortex'), and will be compared with standard HF-TMS in terms of its effectiveness and brain effects. For this, subjects with at least moderate MDD will be randomized to receive daily DTMS or standard HF-rTMS treatment for 4 weeks, and will undergo functional magnetic resonance imaging (fMRI) before and after treatment. fMRI is a neuroimaging technique that allows us to measure which areas of the brain are more or less 'active' in response to specific stimuli at a particular time. During the fMRI sessions, we will use a validated cognitive task on working memory. Our results could eventually lead us, among other things, to identify which depressed patients would be best candidates for receiving either standard HF-rTMS or DTMS, and which areas of the brain should be targeted by these neuromodulation techniques.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
10

participants targeted

Target at below P25 for phase_2 major-depressive-disorder

Timeline
Completed

Started Apr 2013

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

First Submitted

Initial submission to the registry

August 2, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 4, 2011

Completed
1.7 years until next milestone

Study Start

First participant enrolled

April 1, 2013

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

May 28, 2015

Status Verified

May 1, 2015

Enrollment Period

1.8 years

First QC Date

August 2, 2011

Last Update Submit

May 26, 2015

Conditions

Keywords

Major DepressionFunctional Magnetic Resonance ImagingDeep Transcranial Magnetic StimulationRepetitive Transcranial Magnetic StimulationrTMSDTMSfMRIRandomized, Sham-Controlled Trial

Outcome Measures

Primary Outcomes (1)

  • 21-item Hamilton Depression Rating Scale (HAM-D21)

    Pre-post neuromodulation changes on HAM-D21 scores

    week 5

Secondary Outcomes (2)

  • 21-item Hamilton Depression Rating Scale (HAM-D21)

    week 5

  • Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR)

    week 5

Study Arms (2)

Deep Transcranial Magnetic Stimulation

EXPERIMENTAL
Device: Deep Transcranial Magnetic Stimulation

Repetitive Transcranial Magnetic Stimulation

ACTIVE COMPARATOR
Device: Repetitive Transcranial Magnetic Stimulation

Interventions

DTMS will be administered according to the following parameters: 18 Hz in 84 trains of 2 seconds duration, with 20 seconds inter-train interval (3,024 pulses per session) at 120% of the resting motor threshold

Deep Transcranial Magnetic Stimulation

rTMS will be administered according to the following parameters: 18 Hz in 84 trains of 2 seconds duration, with 20 seconds inter-train interval (3,024 pulses per session) at 120% of the resting motor threshold.

Repetitive Transcranial Magnetic Stimulation

Eligibility Criteria

Age25 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Presence of a current major depressive disorder (according to the Diagnostic and Statistical Manual, Fourth Edition, Text Revision \[DSM-IV-TR\]) that has not improved after ≥ 1 but ≤ 3 adequate antidepressant trial(s) in the current episode
  • Baseline score ≥ 21 on the HAM-D21
  • Stable medication regimen (\> 4 weeks)

You may not qualify if:

  • Psychotic features in the current episode
  • Lifetime history of psychotic disorders and/or bipolar I or II disorders
  • Substance or alcohol abuse/dependence in the past 6 months
  • Lifetime history of a major neurological disease (e.g., Parkinson's, stroke)
  • Uncontrolled medical disease (e.g., cardiovascular, renal)
  • Pregnancy and/or lactation
  • Presence of a specific contraindication for DTMS/rTMS/MRI (e.g., personal history of epilepsy, metallic head implant, cardiac pacemaker)
  • Personal history of abnormal brain MRI findings

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Neuromodulation Research Clinic, Douglas Mental Health University Institute

Montreal, Quebec, H4H1R3, Canada

Location

Related Publications (3)

  • Levkovitz Y, Roth Y, Harel EV, Braw Y, Sheer A, Zangen A. A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation. Clin Neurophysiol. 2007 Dec;118(12):2730-44. doi: 10.1016/j.clinph.2007.09.061. Epub 2007 Oct 30.

    PMID: 17977787BACKGROUND
  • Levkovitz Y, Harel EV, Roth Y, Braw Y, Most D, Katz LN, Sheer A, Gersner R, Zangen A. Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients. Brain Stimul. 2009 Oct;2(4):188-200. doi: 10.1016/j.brs.2009.08.002. Epub 2009 Sep 16.

    PMID: 20633419BACKGROUND
  • Isserles M, Rosenberg O, Dannon P, Levkovitz Y, Kotler M, Deutsch F, Lerer B, Zangen A. Cognitive-emotional reactivation during deep transcranial magnetic stimulation over the prefrontal cortex of depressive patients affects antidepressant outcome. J Affect Disord. 2011 Feb;128(3):235-42. doi: 10.1016/j.jad.2010.06.038. Epub 2010 Jul 21.

    PMID: 20663568BACKGROUND

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

  • Marcelo T. Berlim, MD, MSc

    McGill University & Douglas Mental Health University Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Neuromodulation Research Clinic

Study Record Dates

First Submitted

August 2, 2011

First Posted

August 4, 2011

Study Start

April 1, 2013

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

May 28, 2015

Record last verified: 2015-05

Locations