Brain Imaging of rTMS Treatment for Depression

• ClinicalTrials.gov Identifier: NCT01829165
• Recruitment Status: Completed
• First Posted: April 11, 2013
• Results First Posted: April 10, 2018
• Last Update Posted: April 10, 2018
• Sponsor: Stanford University
• Collaborators: The Dana Foundation; National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Amit Etkin, Stanford University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; Depression	Device: rTMS Treatment; Device: Sham rTMS Treatment	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Causal Neural Network-level Understanding of Depression and Its Treatment Through Concurrent TMS and fMRI
• Study Start Date: September 2012
• Actual Primary Completion Date: January 20, 2017
• Actual Study Completion Date: January 20, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Clinician Administered HAM-D [ Time Frame: Baseline; Day 10; Day 20 ]
   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.

Other Outcome Measures:

1. fMRI/TMS Assessed Neural Network Connectivity [ Time Frame: Up to 3 months. ]
   From pre- to post-treatment, improvement will be based on enhanced functional connectivity.
2. Implicit Emotion Regulation [ Time Frame: Up to 3 months ]
   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.
3. fMRI-assessed Resting Connectivity [ Time Frame: Up to 3 months. ]
   From pre- to post-treatment of patients with high-frequency repetitive TMS (rTMS) improvement shall be measured by normalization of baseline network-level deficits.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

Sponsors and Collaborators

Stanford University

The Dana Foundation

National Institute of Mental Health (NIMH)

  Study Documents (Full-Text)

Documents provided by Amit Etkin, Stanford University:

Study Protocol and Statistical Analysis Plan  [PDF] January 17, 2018

More Information

Additional Information:

About our lab 

• Responsible Party: Amit Etkin, Principal Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT01829165
• Other Study ID Numbers: 21206; P30MH089888-01 ( U.S. NIH Grant/Contract )
• First Posted: April 11, 2013
• Results First Posted: April 10, 2018
• Last Update Posted: April 10, 2018
• Last Verified: March 2018

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Major; Behavioral Symptoms; Mood Disorders; Mental Disorders