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

NCT03523507 | Terminated FDA Device

• 1 other identifier: 898115
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Traumatic Brain Injury; Concussion, Mild; Depressive Symptoms

Keywords

Repetitive Transcranial Magnetic Stimulation; Military

Outcome Measures

Primary Outcomes (1)

• Improvement in Depressive Symptoms

  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.

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

Secondary Outcomes (7)

• Changes in Cognitive Function

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

• Changes in TBI-related Symptoms

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

• Changes in PTSD-related Symptoms

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

• Changes in Tinnitus-related Symptoms

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

• Frequency of Adverse Effects

  Change between baseline, post-treatment (i.e., within 10 days of treatement completion), and 6-month follow-up

Study Arms (2)

Active: rTMS

EXPERIMENTAL

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

Sham: rTMS

SHAM COMPARATOR

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

Interventions

Active: rTMS DEVICE

Daily sessions will consist of 3000 left-sided excitatory pulses at 10 Hz (with 4-second trains and 26-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.

Active: rTMS

Sham: rTMS DEVICE

Daily sessions will consist of the same total number of sham pulses, designed to have similar sound and tactile sensation, without producing active stimulation.

Sham: rTMS

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-64
• Current or former US military service member
• Eligible for care at DoD facilities
• Able to provide written, informed consent in English
• History of concussive TBI:
• \>6 months prior to consent
• Documented previously in medical records and/or as confirmed by the TBI Screener
• Must meet Criterion A of the DSM-5 criteria for Major Depressive Disorder as determined by a trained assessor
• Baseline MADRS \>10

You may not qualify if:

• Elevated risk of seizures:
• Prior history of unprovoked seizures other than within 24 hours of concussive TBI
• Family history of seizures
• History of TBI resulting in penetrating trauma based on the TBI Screener
• Presence of intracranial tumor or intraparenchymal hemorrhage based on the structural MRI scan
• Heavy alcohol consumption within 48 hours, prior to any treatment session
• Receiving tricyclic antidepressants or neuroleptics at doses that lower seizure threshold
• Contraindications to awake 3T MRI without contrast:
• Ferromagnetic implants or metallic shrapnel
• Severe claustrophobia
• Unable to lie awake, supine, stationary, with reasonable comfort in the scanner for approximately 45 minutes
• Markedly distorted functional brain anatomy such that rsfMRI targeting cannot be performed
• History of severe or recent uncontrolled heart disease
• Presence of a cardiac pacemaker or intracardiac lines
• Implanted neurostimulators and medication pumps

Sponsors & Collaborators

• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• Center for Neuroscience and Regenerative Medicine (CNRM): collaborator

Study Sites (2)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, 22060, United States

Location

Related Publications (2)

• Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ, Leuthardt EC, Corbetta M. Resting state network estimation in individual subjects. Neuroimage. 2013 Nov 15;82:616-633. doi: 10.1016/j.neuroimage.2013.05.108. Epub 2013 Jun 2.

  PMID: 23735260 BACKGROUND

• Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, Carvalho AF. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry. 2017 Feb 1;74(2):143-152. doi: 10.1001/jamapsychiatry.2016.3644.

  PMID: 28030740 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Concussion; Depression

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Head Injuries, Closed; Wounds, Nonpenetrating; Behavioral Symptoms; Behavior

Study Officials

• David L Brody, MD, PhD

  Center for Neuroscience and Regenerative Medicine (CNRM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: May 14, 2018
• Study Start: July 1, 2019
• Primary Completion: October 27, 2020
• Study Completion: October 27, 2020
• Last Updated: November 3, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (2)