Transcranial Magnetic Stimulation for Adolescent Depression (TMSAD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by University of Calgary
Sponsor:
Information provided by (Responsible Party):
Frank MacMaster, PhD, University of Calgary
ClinicalTrials.gov Identifier:
NCT01731678
First received: November 3, 2012
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

Major depression (or MDD) in adolescents is a major public health problem. MDD affects approximately 15% of adolescents; it is associated with impairment in social, family, and academic functioning, and it is a major risk factor for suicide - a leading cause of death in adolescents . Unfortunately, there is a paucity of treatment options for this age group. Selective serotonin reuptake inhibitors (SSRIs) are the only class of medications approved for treating MDD in adolescents, but rates of remission following treatment with SSRIs are only 30 to 45 percent. Cognitive behavior therapy is associated with similar remission rates and access is limited. Most adolescents will require more than one therapeutic intervention in order to achieve full symptom control. Collectively, there is overwhelming evidence that additional treatment options are urgently needed to improve outcomes for teens with MDD. One novel treatment for adolescent MDD is repetitive transcranial magnetic stimulation (rTMS). Studies in children have been limited (a total of 23 cases). This is surprising given the evidence suggesting younger adult subjects with MDD respond better to rTMS (56% response rate) than older subjects. This limited experience with rTMS for adolescent MDD represents a substantial gap in the knowledge, recently recognized in publications calling for further study of rTMS in adolescent depression. Most importantly, the mechanism of action of rTMS in adolescent MDD is not well understood. The objective of this application is to develop an understanding of the brain alterations associated with the positive clinical changes that occur with rTMS in adolescent MDD. Such knowledge will provide the basis for pursuing rTMS for adolescent MDD as a rational therapeutic technique.

Specific Aim: To compare the effect of rTMS on DLPFC glutamate concentration in adolescent MDD. The investigators hypothesize an increase (normalization to controls) in DLPFC glutamate after three weeks of rTMS. Furthermore, the change in glutamate concentration will correlate with a change in MDD symptoms.


Condition Intervention
Major Depressive Disorder
Procedure: Transcranial Magnetic Stimulation

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transcranial Magnetic Stimulation for Adolescent Depression

Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale [ Time Frame: Three weeks ] [ Designated as safety issue: No ]
    A reduction of Hamilton Depression Rating Scale score of 50% is considered positive response


Other Outcome Measures:
  • Interim Analysis - rTMS tolerability scale [ Time Frame: After the first 10 patients are completed ] [ Designated as safety issue: Yes ]
    There will be an interim analysis to review safety, tolerability (as measured by our rTMS tolerability scale) after the first 10 rTMS patients. Should there be significant concerns, the team will terminate the study. Ten was selected as it is close to previous reports and should be informative.

  • Interim Analysis - Ham-D [ Time Frame: After the first 10 patients are completed ] [ Designated as safety issue: Yes ]
    There will be an interim analysis to review response (Ham-D) after the first 10 rTMS patients. Should there be significant concerns, the team will terminate the study. Ten was selected as it is close to previous reports and should be informative.


Estimated Enrollment: 50
Study Start Date: November 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transcranial Magnetic Stimulation
The standardized treatment location will be the left DLPFC. Anatomical T1 images from the pre-intervention MRI will be loaded into our Transcranial Magnetic Stimulation (TMS) lab neuronavigation software (Brainsight2, Rogue Research, Montreal). Following 3D co-registration of the TMS coil with the patient's MRI images and head, the coil will be placed over the left DLPFC (tangential to scalp, angle of 45 degrees to midline). Interventional repetitive TMS (rTMS) (Magstim Rapid2, Wales, UK) will consist of 40 suprathreshold (120% RMT) pulses over 4 seconds (10 Hz) with an inter-train interval of 26 seconds. Treatment sessions will last 37.5 minutes (75 trains/3000 pulses). Treatments will occur on each weekday for three weeks (15 days total).
Procedure: Transcranial Magnetic Stimulation
The standardized treatment location will be the left DLPFC. Anatomical T1 images from the pre-intervention MRI will be loaded into our Transcranial Magnetic Stimulation (TMS) lab neuronavigation software (Brainsight2, Rogue Research, Montreal). Following 3D co-registration of the TMS coil with the patient's MRI images and head, the coil will be placed over the left DLPFC (tangential to scalp, angle of 45 degrees to midline). Interventional repetitive TMS (rTMS) (Magstim Rapid2, Wales, UK) will consist of 40 suprathreshold (120% RMT) pulses over 4 seconds (10 Hz) with an inter-train interval of 26 seconds. Treatment sessions will last 37.5 minutes (75 trains/3000 pulses). Treatments will occur on each weekday for three weeks (15 days total).

  Eligibility

Ages Eligible for Study:   12 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age (12-22 years),
  • MDD failing to respond to at least one SSRI trial (minimum 8 weeks treatment at an adequate dose; determined retrospectively), and
  • informed consent. Healthy controls with no psychiatric history (who do not receive rTMS) will undergo MRI scans to allow for comparison with MDD patients.

Exclusion Criteria:

  • previous seizures or epilepsy,
  • hypertension,
  • additional neurological or psychiatric diagnoses (specifically: bipolar disorder, psychosis, pervasive developmental disorder, eating disorders, and post-traumatic stress disorder).

As 3T MRI will be used, pregnancy is exclusionary.

  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: NCT01731678

Contacts
Contact: Frank P MacMaster, PhD 403-955-2784 fmacmast@ucalgary.ca

Locations
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Frank P MacMaster, PhD    403-955-2784    fmacmast@ucalgary.ca   
Sponsors and Collaborators
University of Calgary
Investigators
Principal Investigator: Frank P MacMaster, PhD University of Calgary
  More Information

No publications provided

Responsible Party: Frank MacMaster, PhD, Cuthbertson and Fischer Chair in Paediatric Mental Health, University of Calgary
ClinicalTrials.gov Identifier: NCT01731678     History of Changes
Other Study ID Numbers: E-24656
Study First Received: November 3, 2012
Last Updated: November 21, 2012
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

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

ClinicalTrials.gov processed this record on October 23, 2014