Clinical trial NCT02980484: fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI
Official title: fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depressive Disorder
Traumatic Brain Injury
Keywords: rTMS
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-12-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized double-blind sham-controlled trial with an optional open-label crossover extension for subjects randomized to sham group.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvement in depressive symptoms
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Secondary outcomes:
measure: Changes in resting-state fMRI and DTI findings
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
measure: Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
measure: Changes in temperament and character
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
measure: Response and remission rates in depressive symptoms
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
measure: Changes in headache scales
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
measure: Changes in tinnitus score
timeFrame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Shan H Siddiqi, MD
role: PRINCIPAL_INVESTIGATOR
References: