fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI
|ClinicalTrials.gov Identifier: NCT02980484|
Recruitment Status : Terminated (Investigators left the institution for unrelated reasons)
First Posted : December 2, 2016
Last Update Posted : March 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder Traumatic Brain Injury||Procedure: Active Procedure: Sham||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Randomized double-blind sham-controlled trial with an optional open-label crossover extension for subjects randomized to sham group.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury|
|Study Start Date :||August 2016|
|Actual Primary Completion Date :||August 2017|
|Actual Study Completion Date :||August 2017|
Experimental: Active rTMS
Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.
Repetitive transcranial magnetic stimulation (rTMS) will be applied to the left dorsolateral prefrontal cortex (DLPFC) (4000 pulses, 10 Hz, 5-sec trains, 25-sec inter-train interval) followed by the right DLPFC (1000 pulses, 1 Hz frequency, single train). The DLPFC will be identified using individual subject-level resting-state network estimation (Hacker et al, 2013). Each treatment will be completed over the course of 1 hour, and each subject will receive a total of 20 treatments over the course of 20 consecutive weekdays.
Sham Comparator: Sham/crossover rTMS
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.
Treatment that looks and feels similar to active rTMS will be administered as a sham treatment.
- Improvement in depressive symptoms [ Time Frame: 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.
- Changes in resting-state fMRI and DTI findings [ Time Frame: 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.
- Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries [ Time Frame: 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 [ Time Frame: 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.
- Response and remission rates in depressive symptoms [ Time Frame: 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 headache scales [ Time Frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks) ]Mean percentage improvement in HIT-6 headache scores
- Changes in tinnitus score [ Time Frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks) ]Mean percentage improvement in tinnitus severity score and mini-Tinnitus Questionnaire scores
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980484
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Shan H Siddiqi, MD||Washington University School of Medicine|