fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI

Phase 2

Terminated

• Conditions: Major Depressive Disorder; Traumatic Brain Injury
• Interventions: Procedure: Active; Procedure: Sham

• Registration Number: NCT02980484
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This pilot study aims to investigate the efficacy of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in treatment of major depression associated with traumatic brain injury (TBI). Half of patients will receive active treatment, while the other will receive a sham treatment with the option of receiving open-label active treatment afterwards.

Detailed Description

rTMS is an FDA-approved treatment for major depressive disorder, but its utility has not yet been investigated for major depression associated with traumatic brain injury.

This will be a prospective double-blind randomized sham-controlled crossover study. Patients in the treatment group will receive 20 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC. The DLPFC will be identified as target by using individual subject-level resting state network estimation (Hacker et al, 2013). Patients in the control group will receive 20 sham treatments designed to be visibly indistinguishable from active treatment, and will subsequently have the option to be crossed over to receive active treatment with the aforementioned protocol. A subgroup of patients in each group will receive more detailed diffusion imaging (diffusion tensor and diffusion kurtosis imaging) and resting state fMRI scans before and after the treatment in order to assess for changes in white matter integrity and functional connectivity associated with the treatment.

Study Timeline

• Study First Submitted: 2016-02-25
• Study Start: 2016-08
• Study First Submitted QC: 2016-11-29
• Study First Posted: 2016-12-02
• Primary Completion: 2017-08
• Study Completion: 2017-08
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-26
• Last Update Posted: 2018-03-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active rTMS	Active	Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.
Sham/crossover rTMS	Sham	Rather than receiving active treatment, subjects will receive sham treatment designed to be indistinguishable from active treatment to the patient. After completion of the sham course, patients will have the option to receive open-label active treatment at no cost.

Primary Outcome Measures

Name	Time	Method
Improvement in depressive symptoms	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	This will be measured as the mean percentage change in baseline scores on Montgomery-Asberg Depression Rating Scale (MADRS) before treatment and immediately after the 4-week treatment period.

Secondary Outcome Measures

Name	Time	Method
Changes in headache scales	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	Mean percentage improvement in HIT-6 headache scores
Changes in resting-state fMRI and DTI findings	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	MRI imaging will be conducted to assess resting-state functional connectivity using functional magnetic resonance imaging (fMRI). More detailed structural (DTI) and functional (fMRI) imaging will be measured in a subgroup of patients.
Response and remission rates in depressive symptoms	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	Percentage of subjects achieving response (\>50% improvement in MADRS) and remission (final MADRS score \<7) before treatment and immediately after the 4-week treatment period.
Changes in tinnitus score	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	Mean percentage improvement in tinnitus severity score and mini-Tinnitus Questionnaire scores
Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	The NIH Toolbox Cognitive battery will be used to determine change in cognitive symptoms with treatment. Emotional battery and TBI-QoL scales will be used to determine change in general neuropsychiatric symptom burden.
Changes in temperament and character	Difference between pre-treatment (baseline) and post-treatment (4 weeks)	Will administer the 140-question Temperament and Character Inventory (TCI-R140) before and after treatment.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States