Neural Predictors and Longitudinal Neural Correlates of Deep Transcranial Magnetic Stimulation for Treating Major Depression

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Brainsway
Information provided by (Responsible Party):
MARCELO T. BERLIM, Douglas Mental Health University Institute
ClinicalTrials.gov Identifier:
NCT01409317
First received: August 2, 2011
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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, 80 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.


Condition Intervention Phase
Major Depressive Disorder
Device: Deep Transcranial Magnetic Stimulation
Device: Repetitive Transcranial Magnetic Stimulation
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Neural Predictors and Longitudinal Neural Correlates of Clinical Improvement After Standard or Deep Transcranial Magnetic Stimulation in Major Depression: A Randomized Study

Further study details as provided by Douglas Mental Health University Institute:

Primary Outcome Measures:
  • 21-item Hamilton Depression Rating Scale (HAM-D21) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
    Pre-post neuromodulation changes on HAM-D21 scores


Secondary Outcome Measures:
  • 21-item Hamilton Depression Rating Scale (HAM-D21) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
    Response to treatment is defined as a ≥ 50% reduction in the scores of the HAM-D21. Remission is defined as a HAM-D21 score ≤ 8.

  • Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) [ Time Frame: week 5 ] [ Designated as safety issue: No ]
    Response is defined as a ≥ 50% reduction in the scores of the QIDS-SR. Remission is defined as a QIDS-SR score ≤ 5.


Estimated Enrollment: 80
Study Start Date: April 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deep Transcranial Magnetic Stimulation Device: Deep Transcranial Magnetic Stimulation
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
Active Comparator: Repetitive Transcranial Magnetic Stimulation Device: Repetitive 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.

  Eligibility

Ages Eligible for Study:   25 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409317

Locations
Canada, Quebec
Neuromodulation Research Clinic, Douglas Mental Health University Institute
Montreal, Quebec, Canada, H4H1R3
Sponsors and Collaborators
Douglas Mental Health University Institute
Brainsway
Investigators
Principal Investigator: Marcelo T. Berlim, MD, MSc McGill University & Douglas Mental Health University Institute
  More Information

Additional Information:
Publications:
Responsible Party: MARCELO T. BERLIM, Director, Neuromodulation Research Clinic, Douglas Mental Health University Institute
ClinicalTrials.gov Identifier: NCT01409317     History of Changes
Other Study ID Numbers: DTMS-ERB11/28-2011
Study First Received: August 2, 2011
Last Updated: April 28, 2014
Health Authority: Canada: Health Canada

Keywords provided by Douglas Mental Health University Institute:
Major Depression
Functional Magnetic Resonance Imaging
Deep Transcranial Magnetic Stimulation
Repetitive Transcranial Magnetic Stimulation
rTMS
DTMS
fMRI
Randomized, Sham-Controlled Trial

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014