Imaging Biomarkers for TMS Treatment of Depression

Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to learn more about how rTMS works to reduce the symptoms of depression. This information can be used to improve the effectiveness of the treatment. The study will use functional magnetic resonance imaging (fMRI) to examine changes in brain function after treatment with rTMS. fMRI is a safe and painless technique that allows investigators to observe the brain at work. The investigators will use fMRI to see what regions of the brain become active when you perform a concentration task and how that activation is changed after rTMS.

Official Title
-----------------
Imaging Biomarkers for TMS Treatment of Depression

Conditions
-----------------
Depression

Intervention / Treatment
-----------------
* Device: repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary diagnosis of major depressive disorder Male and female subjects, ages 22-65 Have failed at least 1 antidepressant medication at adequate dose and duration On stable antidepressant medication regimen for at least 4 weeks prior to TMS therapy Exclusion Criteria: Diagnosed with a psychotic, bipolar, obsessive-compulsive or post-traumatic stress disorder Active substance abuse, including alcohol Medical and/or neurological condition that could affect your brain function or risk of seizure, including a stroke, epilepsy, or a closed head injury; No presence of an implanted device like a pacemaker/neurostimulator or metal in the head or body; Pregnant or trying to get pregnant Failed to respond to an adequate course of electroconvulsive therapy (ECT) Previous treatment with TMS Current depressive episode longer than 5 years

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS<br>20 active sessions, within a 4 week period, where subjects receive the same repetitive Transcranial Magnetic Stimulation (rTMS) treatment parameters as the FDA-approved device label (10 Hz) to a targeted area of the brain. After these sessions, a second fMRI will be completed then 5 additional tapering treatments of rTMS over a 2 week period. | Device: repetitive Transcranial Magnetic Stimulation (rTMS)<br>* 20 active sessions, within a 4 week period, where subjects receive the same repetitive Transcranial Magnetic Stimulation (rTMS) treatment parameters as the sham arm.<br>* Other names: Sham treatment;|
| Sham Comparator: Sham rTMS<br>20 sham sessions, within a 4 week period, where subjects receive inactive treatments (0 Hz) of repetitive Transcranial Magnetic Stimulation (rTMS). After 20 sessions and completion of a second fMRI scan, patients in this group will then be unblinded and transitioned to the active arm and will receive a full course (25 sessions) of active rTMS over a 6 week period. | Device: repetitive Transcranial Magnetic Stimulation (rTMS)<br>* 20 active sessions, within a 4 week period, where subjects receive the same repetitive Transcranial Magnetic Stimulation (rTMS) treatment parameters as the sham arm.<br>* Other names: Sham treatment;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive Symptoms at 4 Weeks | MADRS: Montgomery Asberg Depression Rating Scale Range: 0 - 60 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression | 4 weeks after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Symptoms at 4 Weeks- Secondary | Depressive symptoms as measured by the 17-item Hamilton Depression Rating Scale (HRSD17) Range: 0-53 Normal: 0-7 Mild: 8 - 13 Moderate 14 - 18 Severe: 19-22 Very severe > 22 | 4 weeks after baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TMS, Major Depression, Major Depressive Disorder, rTMS