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

This study is currently recruiting participants.
Verified November 2016 by Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02980484
First Posted: December 2, 2016
Last Update Posted: December 2, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose
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.

Condition Intervention
Major Depressive Disorder Traumatic Brain Injury Procedure: Active Procedure: Sham

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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


Estimated Enrollment: 50
Study Start Date: August 2016
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active
Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.
Procedure: Active
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
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.
Procedure: Sham
Treatment that looks and feels similar to active rTMS will be administered as a sham treatment.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980484


Contacts
Contact: Shan H Siddiqi, MD 6364659742 siddiqis@psychiatry.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, MO, Missouri, United States, 63110
Principal Investigator: Shan H Siddiqi, MD         
Principal Investigator: David L Brody, MD, PhD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Shan H Siddiqi, MD Washington University School of Medicine
  More Information

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02980484     History of Changes
Other Study ID Numbers: 201603051
First Submitted: February 25, 2016
First Posted: December 2, 2016
Last Update Posted: December 2, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified neuroimaging data will be submitted to FITBIR (Federal Interagency TBI Research)

Keywords provided by Washington University School of Medicine:
rTMS

Additional relevant MeSH terms:
Depression
Depressive Disorder
Brain Injuries
Depressive Disorder, Major
Brain Injuries, Traumatic
Behavioral Symptoms
Mood Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries