Brain Imaging of rTMS Treatment for Depression

A Causal Neural Network-level Understanding of Depression and Its Treatment Through Concurrent TMS and fMRI

The overarching goal of this research program is to elucidate causal and directional neural network- level abnormalities in depression, and how they are modulated by an individually-tailored, circuit-directed intervention. By using concurrent TMS and fMRI, the investigators can overcome a major limitation of neuroimaging - the inability to demonstrate causality. The investigators' findings will serve as a platform for future studies wherein TMS treatment can be directly guided by the investigators' ability to image and causally manipulate specific neural networks.

Aim 1: To examine causal interactions between two major brain networks in depression.

Aim 2: To examine the impact of antidepressant TMS on causal network abnormalities in depression.

Hypothesis 1: Depressed subjects will show blunted responses, compared to healthy controls, in two targeted and interacting networks, using concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI).

Hypothesis 2: Treatment of patients with high-frequency repetitive TMS (rTMS) will result in normalization of baseline network-level deficits, and be predicted by degree of baseline network abnormalities.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Device: rTMS Treatment; Device: Sham rTMS Treatment

Detailed Description

This study has a single primary outcome measure and other measures are exploratory. Previous versions of this study record incorrectly listed some exploratory outcome measures as secondary.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, ages 18 to 50
• Depression assessed through phone screen
• Must comprehend English well to ensure adequate comprehension of the fMRI and TMS instructions, and of clinical scales
• Has failed >1 previous adequate antidepressant medication trials
• Right-handed
• No current or history of neurological disorders
• No seizure disorder or risk of seizures

Exclusion Criteria:

• Any contraindication to being scanned in the 3T scanners at the Lucas Center or CNI such as having a pacemaker or implanted device that has not been cleared for scanning at the Lucas Center or CNI
• Any unstable medical condition, any significant CNS neurological condition such as stroke, seizure, tumor, hemorrhage, multiple sclerosis, etc
• Current rTMS treatment or prior treatment failure with rTMS
• Current electroconvulsive therapy (ECT) or prior treatment failure with ECT
• Currently pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS Treatment; rTMS will be delivered for 20 sessions over 4 weeks. Active 10 Hz rTMS will be delivered using neuro-navigation based on participants' own fMRI images. Daily treatment regiments will last 36.5 minutes and rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sessions for adverse events and/or side effects.	Device: rTMS Treatment; MRI-compatible TMS stimulator; Other Names: Magstim Stimulator; Magventure Stimulator
Sham Comparator: Sham Treatment; rTMS will be delivered for 20 sessions over 4 weeks. Placebo 10Hz rTMS will be delivered through sham stimulation electrodes. The rTMS coil will be positioned using neuro-navigation based on participants' own fMRI images, mimicking active rTMS treatment. Daily treatment regiments will last 36.5minutes and sham rTMS will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS sham sessions for adverse events and/or side effects. Upon completing the sham 20 sessions participants are unblinded and offered 20 further treatments of guaranteed open-label treatment. The open-label treatment would follow the active rTMS treatment protocol.	Device: Sham rTMS Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered HAM-D	The Hamilton Depression Rating Scale (HAM-D) is a 24-item clinician-administered assessment utilized as a way of determining a patient's level of depression before, during, and after treatment. It takes approximately 15-20 minutes to complete the interview and score the results. Subscale scores are 0-2 (10 questions), 0-3 (2 questions), and 0-4 (12 questions). Subscales are totaled for an overall score (range 0 -76). For the overall score and all subscales, lower scores correspond to fewer symptoms, and higher scores correspond more symptoms.	Baseline; Day 10; Day 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI/TMS Assessed Neural Network Connectivity	From pre- to post-treatment, improvement will be based on enhanced functional connectivity.	Up to 3 months.
Implicit Emotion Regulation	Implicit emotion regulation assessed through emotion conflict task performed during functional imaging. Performance based on reaction time and recruitment of emotion regulation regions during the task.	Up to 3 months
fMRI-assessed Resting Connectivity	From pre- to post-treatment of patients with high-frequency repetitive TMS (rTMS) improvement shall be measured by normalization of baseline network-level deficits.	Up to 3 months.

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Mental Health (NIMH); The Dana Foundation

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): January 20, 2017
• Study Completion (Actual): January 20, 2017

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: April 8, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: March 10, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 21206; P30MH089888-01 (U.S. NIH Grant/Contract)