rTMS for MDD: 5.5cm Rule vs. F3 Targeting

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5.5cm Rule Group; 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; 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.
Active Comparator: F3 Group; 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; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Nicholas Trapp
• Investigators: Principal Investigator: Nicholas T Trapp, M.D., University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): September 13, 2022
• Study Completion (Actual): September 13, 2022

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; rTMS; TMS; Targeting; F3; 5.5cm rule
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 201709834

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes