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Trial record 2 of 3 for:    Brody | TBI (Traumatic Brain Injury) | United States

fMRI-neuronavigated rTMS Treatment for Symptoms of Depression Associated With Concussive TBI in the Military Population

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ClinicalTrials.gov Identifier: NCT03523507
Recruitment Status : Not yet recruiting
First Posted : May 14, 2018
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Center for Neuroscience and Regenerative Medicine (CNRM)
Information provided by (Responsible Party):
Henry M. Jackson Foundation for the Advancement of Military Medicine

Brief Summary:

This study aims to investigate the efficacy and tolerability of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in the treatment of depressive symptoms in service members with a history of concussive traumatic brain injury (TBI).

Up to ninety participants will be randomized to active or sham treatment. Participants randomized into the active group will receive 20 sessions of left-sided dorsolateral prefrontal cortex (DLFPC) high-frequency rTMS, followed by right-sided DLFPC low-frequency rTMS. The DLPFC treatment area will be identified by using individual subject-level resting state network estimation (Hacker et al., 2013). Participants randomized into the sham treatment group will receive 20 sham treatments designed to have similar sound and tactile sensation, without producing active treatment. Participants will also be asked to complete regular follow-up evaluations for up to a total of six follow-up sessions. Those who do not respond to the treatment will have the option to receive active treatment through this study regardless of group assignment to active or sham.


Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Concussion, Mild Depressive Symptoms Device: Active: rTMS Device: Sham: rTMS Not Applicable

Detailed Description:

This study aims to investigate the efficacy and tolerability of individual connectome-targeted repetitive transcranial magnetic stimulation (ICT-rTMS) treatment to enhance the rehabilitation of service members with symptoms of depression and history of concussive traumatic brain injury (TBI).

This will be a multi-site, double-blinded, sham-controlled, prospective, randomized interventional trial. Up to ninety participants will be block randomized to active (ICT-rTMS) or sham treatment. Participants will receive 20 sessions of ICT-rTMS over approximately 5 weeks.

Resting-state functional magnetic resonance imaging (rsfMRI) and structural MRI will be obtained at baseline to allow for the calculation of connectome-targeted treatment coordinates and ensure the absence of structural abnormalities. The rsfMRI scan at baseline will also be used to establish the baseline for the secondary imaging outcome measures.

Treatment sessions will consist of high-frequency left dorsolateral prefrontal cortex (DLPFC) stimulation for 4,000 pulses followed by low-frequency right DLPFC stimulation for 1,000 pulses for a total stimulation time of approximately one hour per session. This protocol was chosen based on a recent meta-analysis (Brunoni et al., 2017) indicating that amongst the various treatment protocols, priming the low frequency right hemisphere stimulation with a high frequency left hemisphere stimulation led to the greatest efficacy for treatment of Major Depressive Episodes. Additionally, the overwhelming majority of the literature in TMS for depression targets the stimulation to DLPFC and the FDA has approved repetitive transcranial magnetic stimulation (rTMS) to DLPFC for the treatment of medication-resistant major depressive disorder (MDD).

The primary outcome will be change in depression severity from baseline to post-treatment. The primary analysis will be a comparison between the ICT-rTMS and sham groups. Secondary outcome measures utilized will include cognitive, quality of life, and emotional regulation measures, as well as imaging changes. Additional analyses will include durability of effects during the 6 months following treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Sham-controlled, Double-blinded Study of Bilateral Prefrontal Individual Connectome-targeted Repetitive Transcranial Magnetic Stimulation to Treat the Symptoms of Depression Associated With Concussive Traumatic Brain Injury.
Estimated Study Start Date : May 1, 2019
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active: rTMS
Participants will receive 20 bilateral treatment sessions provided over approximately a 5-week period. Daily sessions entail approximately 60 minutes of time.
Device: Active: rTMS
Daily sessions will consist of 4000 left-sided excitatory pulses at 10 Hz (with 5-second trains and 20-second inter-train interval) followed by 1000 right-sided inhibitory pulses at 1 Hz (in a single train). The DLPFC treatment target will be determined using individualized resting-state network mapping.

Sham Comparator: Sham: rTMS
Sham: Repetitive Transcranial Magnetic Stimulation; Participants will receive sham treatment designed to have similar sound and tactile sensation, without producing active stimulation.
Device: Sham: rTMS
Daily sessions will consist of the same total number of sham pulses, designed to have similar sound and tactile sensation, without producing active stimulation.




Primary Outcome Measures :
  1. Improvement in Depressive Symptoms [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Compare change in overall Montgomery-Asberg Depression Rating Scale (MADRS) scores between participants randomized to ICT-rTMS and those randomized to blinded sham stimulation. The overall score ranges from 0 to 60 with a higher overall score indicating more severe depression.


Secondary Outcome Measures :
  1. Changes in Cognitive Function [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Assess changes in cognitive function and emotion processing as measured by the Automated Neuropsychological Assessment Metric (ANAM).

  2. Changes in TBI-related Symptoms [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Assess changes in TBI-related symptoms as reflected by the TBI-QOL.

  3. Changes in PTSD-related Symptoms [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Assess changes in PTSD-related symptoms as reflected by the PTSD Checklist for DSM-5 (PCL-5).

  4. Changes in Tinnitus-related Symptoms [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    To assess changes in tinnitus-related symptoms as reflected by the Mini Tinnitus Questionnaire (Mini TQ-12).

  5. Frequency of Adverse Effects [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Compare the frequency and severity of adverse effects between those randomized to ICT-rTMS and those randomized to blinded sham stimulation.

  6. Changes in Psychotherapeutic Changes [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Compare the number, dose, and/or type of adjunctive treatments undertaken by those randomized to ICT-rTMS as compared to those randomized to blinded sham stimulation.

  7. Changes in Resting-state fMRI [ Time Frame: Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up ]
    Assess changes in resting-state functional connectivity using functional magnetic resonance imaging (fMRI).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-64
  2. Current or former US military service member
  3. Able to provide written, informed consent in English
  4. History of concussive TBI:

    1. >6 months prior to consent
    2. Documented previously in medical records and/or as confirmed by the TBI Screener
  5. Must meet Criterion A of the DSM-5 criteria for Major Depressive Disorder as determined by a trained assessor
  6. Baseline MADRS >10

Exclusion Criteria:

  1. Elevated risk of seizures:

    1. Prior history of unprovoked seizures other than within 24 hours of concussive TBI
    2. History of TBI resulting in penetrating trauma or intraparenchymal hemorrhage
    3. History of intracranial tumor
  2. Contraindications to awake 3T MRI without contrast:

    1. Ferromagnetic implants or metallic shrapnel
    2. Severe claustrophobia
    3. Unable to lie awake, supine, stationary, with reasonable comfort in the scanner for approximately 45 minutes
    4. Markedly distorted functional brain anatomy such that rsfMRI targeting cannot be performed
  3. Life expectancy of less than 6 months
  4. Presence of rapidly progressive illnesses such as late stage cancer, neurodegenerative conditions, major organ failure, etc.

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): NCT03523507


Contacts
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Contact: Charline E Simon, MA (301) 295-6439 charline.simon.ctr@usuhs.edu
Contact: Lindsay M Oberman, PhD (301) 295-6420 lindsay.oberman.ctr@usuhs.edu

Locations
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United States, Maryland
Walter Reed National Military Medical Center Not yet recruiting
Bethesda, Maryland, United States, 20889
Principal Investigator: David L Brody, MD, PhD         
United States, Virginia
Fort Belvoir Community Hospital Not yet recruiting
Fort Belvoir, Virginia, United States, 22060
Principal Investigator: Heechin Chae, MD         
Sponsors and Collaborators
Henry M. Jackson Foundation for the Advancement of Military Medicine
Center for Neuroscience and Regenerative Medicine (CNRM)
Investigators
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Principal Investigator: David L Brody, MD, PhD Center for Neuroscience and Regenerative Medicine (CNRM)

Publications:
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Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
ClinicalTrials.gov Identifier: NCT03523507     History of Changes
Other Study ID Numbers: 898115
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Coded data will be deposited into the following repositories: the Center for Neuroscience and Regenerative Medicine (CNRM) Data Repository and the Federal Interagency Traumatic Brain Injury Research (FITBIR) Database.
Time Frame: Following project completion, a summary of the results will be provided to the site.
Access Criteria: Access to the data located in the CNRM Repository and FITBIR database will be provided by the respective entities.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Henry M. Jackson Foundation for the Advancement of Military Medicine:
Repetitive Transcranial Magnetic Stimulation
Military

Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Concussion
Brain Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Head Injuries, Closed
Wounds, Nonpenetrating
Depression
Behavioral Symptoms
Central Nervous System Diseases
Nervous System Diseases