fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Improvement in depressive symptoms
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults age 18 to 65
- •History of traumatic brain injury (TBI) at least two weeks prior to study initiation
- •Presence of an active major depressive episode as defined by DSM-5 criteria, including depression secondary to traumatic brain injury
- •Baseline score of 10 or greater on Montgomery-Asberg Depression Rating Scale (MADRS)
- •Failure of at least one prior antidepressant trial after the traumatic brain injury
Exclusion Criteria
- •History of:
- •Moderate or severe substance use disorder in the past six months as defined by DSM-5 criteria, with the exception of cannabis and nicotine use disorders.
- •Dementia, as defined by treating neurologist
- •Moderate or severe autism spectrum disorder
- •Bipolar disorder
- •Schizophrenia spectrum disorders
- •Current evidence of:
- •Substance-induced mood disorder
- •Active psychotic symptoms
- •Depression secondary to a general medical illness, with the exception of TBI
- •Dysphoria better explained by a baseline personality disorder than a major depressive episode
- •Dysphoria better explained by a baseline anxiety disorder (including post-traumatic stress disorder) rather than a major depressive episode
- •Active suicidal ideation
- •Contraindications to rTMS treatment:
- •Seizure disorder
- •Significantly elevated seizure risk, as determined by clinician assessment
- •TBI associated with elevated seizure risk, including penetrating injury and/or cortical intraparenchymal hemorrhage
- •Presence of metallic objects within the head
- •Presence of an implanted neurostimulation device within the head
- •Contraindications to MRI
- •Severe claustrophobia
- •Severe pain/illness exacerbated by lying prone in the scanner
- •Presence of non-MRI compatible metal foreign bodies or implants
- •Weight in excess of 350 lbs
- •Shoulder width in excess of maximum tolerable width for scanner
Arms & Interventions
Active rTMS
Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.
Intervention: Active (Procedure)
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.
Intervention: Sham (Procedure)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Changes in headache scales(Difference between pre-treatment (baseline) and post-treatment (4 weeks))
- Changes in resting-state fMRI and DTI findings(Difference between pre-treatment (baseline) and post-treatment (4 weeks))
- Response and remission rates in depressive symptoms(Difference between pre-treatment (baseline) and post-treatment (4 weeks))
- Changes in tinnitus score(Difference between pre-treatment (baseline) and post-treatment (4 weeks))
- Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries(Difference between pre-treatment (baseline) and post-treatment (4 weeks))
- Changes in temperament and character(Difference between pre-treatment (baseline) and post-treatment (4 weeks))