rTMS for MDD: 5.5cm Rule vs. F3 Targeting

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of different treatment locations using repetitive transcranial magnetic stimulation (rTMS) to treat major depressive disorder.

Detailed Description
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Currently there is little standardization between rTMS treatment programs as to what is the best way to localize the left dorsolateral prefrontal cortex, which is the FDA-approved treatment location for clinical rTMS for major depressive disorder (MDD). Different targeting methods yield locations that can vary by up to a few centimeters. By comparing different treatment locations and obtaining neurobehavioral, neuroimaging, cognitive, and neuropsychological measures, this study would provide the opportunity to identify the optimal treatment targeting method when using rTMS for major depressive disorder in a clinical setting. This study will specifically be focusing on comparing the two most common targeting methods: a target 5.5cm anterior to the motor strip on the left prefrontal scalp and the F3 target location on the left prefrontal scalp as identified using the 10-20 EEG system nomenclature.

Official Title
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The Effects of Repetitive Transcranial Magnetic Stimulation Prefrontal Target Location on Outcomes for Major Depressive Disorder

Conditions
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Major Depressive Disorder, Depression

Intervention / Treatment
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* Device: Repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of major depressive disorder Age between 18 and 90 years rTMS is clinically indicated as determined by clinical rTMS physician team at University of Iowa Exclusion Criteria: rTMS contraindication such as implanted ferromagnetic material in the head or history of epilepsy with poorly controlled seizures MRI exclusion criteria (if participating in MRI portion of study) including implanted device such as: Pacemaker Coronary Stent Defibrillator Neurostimulation Or any of the following conditions: Claustrophobia Uncontrolled high blood pressure Poorly controlled atrial fibrillation Significant heart disease Hemodynamic instability Severe kidney disease Pregnant, trying to become pregnant, or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5.5cm Rule Group<br>rTMS will be targeted at a left prefrontal target 5.5cm anterior to the primary motor strip identified on the scalp during motor threshold testing. | Device: Repetitive transcranial magnetic stimulation<br>* Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments.<br>|
| Active Comparator: F3 Group<br>rTMS will be targeted at the left prefrontal scalp target identified as F3 according to the 10-20 EEG system. | Device: Repetitive transcranial magnetic stimulation<br>* Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in MADRS score | Overall change in total MADRS score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Response and remission rates on MADRS | Comparison of the response rate (>50% improvement) and remission rate (score <10) for the MADRS between the 2 groups post-treatment. | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Personality measures | Changes in the Temperament and Character Inventory subscales | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Clinical Global Impression Scale | CGI comparing pre- to post-treatment. | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| PHQ9 changes | Comparison of percentage change in PHQ9 pre- to post-treatment. | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Montreal Cognitive Assessment (MOCA) score changes | Changes in MOCA scores | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Cognitive measures | Changes in NIH Toolbox Cognitive Battery | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Emotion measures | Changes in NIH Toolbox Emotional Battery | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Functional MRI changes | Changes in functional connectivity resting-state MRI pre- to post-treatment | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Structural MRI changes | Changes in structural and volumetrics on MRI pre- to post-treatment | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 
| Neurobehavioral battery changes | Changes in scores on a novel neurobehavioral assessment | Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation, rTMS, TMS, F3, 5.5cm rule, Targeting