Imaging to Improve Brain Stimulation

Targeting Functional Improvement in rTMS Therapy

This study investigates how brains change as a result of a treatment for depression called repetitive transcranial magnetic stimulation (rTMS). People who receive rTMS will have pictures of their brains and brain activity taken by a magnetic resonance imaging (MRI) scanner before and after their treatment, as well as up to three times during the six-week treatment course. These images will be examined to see if the rTMS is placed correctly to help treat their symptoms, and what changes in brain activity are happening during the rTMS treatment

Study Overview

• Status: Active, not recruiting
• Conditions: Depressive Disorder
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Detailed Description

Veteran patients can be referred to receive a Neuromodulation Clinic consult at the Providence VA Medical Center (PVAMC). Following this consultation, patients who are to begin rTMS therapy for the treatment of major depressive disorder (MDD) will be recruited to participate in this study. About 1 week prior to the scheduled beginning of rTMS therapy, research participants who provide informed consent will complete baseline neuropsychological measures. Within a few days of completing these measures, and before beginning rTMS therapy, participants will receive an MRI scan, including structural and functional imaging. Participants will have a similar set of MRI scans up to three times during the course of rTMS therapy, and complete neuropsychological measures at these scanning sessions. A final MRI scan will be conducted within a week of completing the rTMS therapy course, and neuropsychological measures will be completed at this session.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1207
      • VA Palo Alto Health Care System, Palo Alto, CA
  • Rhode Island
    • Providence, Rhode Island, United States, 02908-4734
      • Providence VA Medical Center, Providence, RI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Veterans who receive TMS therapy for the treatment of MDD at the Providence VAMC Neuromodulation Clinic

Description

Inclusion Criteria:

• Veteran beginning TMS therapy for the treatment of MDD at the Providence VAMC Neuromodulation Clinic
• Age between 18 and 80 years
• Able to read, verbalize, understand, and voluntarily sign the informed consent form
• Structured Clinical Interview for DSM-5 (SCID-5) confirmed diagnosis of MDD

Exclusion Criteria:

• Contraindications to MRI (e.g. implanted metal or electronic devices)
• Montreal Cognitive Assessment (MoCA) score < 26
• Pregnant

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Group; All participants enrolled in the study	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Clinical transcranial magnetic stimulation administered as part of usual care for the study population; Other Names: transcranial magnetic stimulation, theta burst transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distance between treatment location and brain target	A marker visible on MRI will be placed on the treatment location for the MRI scan after treatment completion. Functional MRI will be used to localize the dorsolateral prefrontal cortex (DLPFC), the brain region targeted by rTMS. The distance between these two points will be calculated for each participant.	Within one week of the conclusion of clinical rTMS therapy course

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
World Health Organization Disability Assessment Schedule 2.0 36-item version	Scores from the World Health Organization Disability Assessment Schedule 36-item version (WHODAS-36). Self-assessment of global functioning, with scores ranging from 0 (no disability) to 100 (full disability).	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course
Inventory of Depressive Symptoms Self-Report	Scores from the Inventory of Depressive Symptoms Self-Report (IDS-SR). A 30-item self-assessment of depressive symptoms with scores ranging from 0 (no depressive symptoms) to 90 (severe depression).	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course
Patient Health Questionnaire 9-item	Scores from the Patient Health Questionnaire, 9-item version (PHQ-9). A self-assessment of depressive symptoms with scores ranging from 0 (no depressive symptoms) to 27 (severe depression).	Within one week before beginning the clinical rTMS therapy course, and weekly during the clinical rTMS therapy course (typically 6 weeks), including the last day of treatment
Post-Traumatic Stress Disorder Checklist for DSM-5	Scores from the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). A self-assessment of PTSD symptoms with scores ranging from 0 (no PTSD symptoms) to 80 (severe PTSD symptoms)	Within one week before beginning the clinical rTMS therapy course, and weekly during the clinical rTMS therapy course (typically 6 weeks), including the last day of treatment
Veteran's RAND 36-item	Scores from the Veteran's RAND 36-item (VR-36). Assessment of self-reported health quality of life. Includes physical and mental component normed subscores (x=50, sd=10) ranging from 0 (worst health) to 100 (best health).	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional MR imaging changes related to stimulation	Magnetic resonance imaging acquired throughout TMS will be analyzed to evaluate aggregate changes related to stimulation	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course
Functional MR imaging changes predictive of outcomes	Magnetic resonance imaging acquired throughout TMS will be analyzed to evaluate how brain changes can be used to predict outcomes	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course
Functional MR imaging changes over time	Magnetic resonance imaging acquired throughout TMS will be analyzed to evaluate how MR imaging of an individual changes over time	Within one week before beginning clinical rTMS therapy course, 3 times during the clinical rTMS therapy course (typically 6 weeks), and within one week after the conclusion of clinical rTMS therapy course

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Brown University; VA Palo Alto Health Care System
• Investigators: Principal Investigator: Allyson C Rosen, PhD, VA Palo Alto Health Care System, Palo Alto, CA; Principal Investigator: Noah S. Philip, MD, Providence VA Medical Center, Providence, RI

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Actual): September 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder
• Other Study ID Numbers: D3152-R-1; N2864-C (Other Grant/Funding Number: Center for Neurorestoration and Neurotechnology)

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.: No