rTMS for Military TBI-related Depression

NCT05426967 | Recruiting DMC FDA Device

• 1 other identifier: USUHS-2020-050
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to investigate the efficacy, safety, and tolerability of two dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) protocols to alleviate symptoms of depression in United States (U.S.) military service members and veterans with a history of concussion/mild traumatic brain injury (TBI).

Conditions

Depressive Symptoms; Mild Traumatic Brain Injury; Concussion

Keywords

Transcranial Magnetic Stimulation (TMS); Depressive Symptoms; Concussion; Mild Traumatic Brain Injury (TBI); Functional Magnetic Resonance Imaging (fMRI)

Outcome Measures

Primary Outcomes (6)

• Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores

  Change in Montgomery-Asberg Depression Rating Scale scores from baseline to post-intervention between groups. The Scale is designed to measure depression severity and consists of 10 items, each of which is scored on a Likert scale from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  Baseline to post-intervention, within 10 working days of the final rTMS session

• Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores in a Subgroup

  Change in Montgomery-Asberg Depression Rating Scale scores between groups from Baseline to post-intervention in participants who complete ≥80% of rTMS sessions. The Scale is designed to measure depression severity and consists of 10 items, each of which is scored on a Likert scale from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  Baseline to post-intervention, within 10 working days of the final rTMS session

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores from Baseline to 6-month follow-up

  Change in Montgomery-Asberg Depression Rating Scale scores from baseline to 6-month follow-up between groups. The Scale is designed to measure depression severity and consists of 10 items, each of which is scored on a Likert scale from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.

  Baseline to 6 months

• Comparison of Treatment Response or Remission in Montgomery-Asberg Depression Rating Scale (MADRS) Scores

  Comparison of proportion of participants in each condition achieving treatment response ≥50% improvement in MADRS) or remission (MADRS ≤10)

  Baseline to post-intervention, within 10 working days of the final rTMS session

• Comparison of Duration of Remission of Depressive Symptoms in Montgomery-Asberg Depression Rating Scale (MADRS) Scores

  Comparison of duration of remission of depressive symptoms in Montgomery-Asberg Depression Rating Scale (MADRS) Scores between groups assessed monthly during follow-up

  Follow-up Period, from 1-6 months after the final rTMS session

• Comparison of Frequency of Adverse Events

  Comparison of AEs between groups

  Baseline to post-intervention, within 10 working days of the final rTMS session

Secondary Outcomes (11)

• Comparison of Change in Inventory of Depressive Symptomatology-Self Report (IDS-SR) Scores from Baseline to post-intervention

  Baseline to post-intervention, within 10 working days of the final rTMS session

• Comparison of Change in Symptoms of Major Depressive Disorder Scale (SMDDS) Scores from Baseline to Post-intervention

  Baseline to post-intervention, within 10 working days of the final rTMS session

• Comparison of Change in Inventory of Depressive Symptomatology-Self Report (IDS-SR) Scores from Baseline to 6-month follow-up

  Baseline to 6-month follow-up

• Comparison of Change in Symptoms of Major Depressive Disorder Scale (SMDDS) Scores from Baseline to 6-month follow-up

  Baseline to 6-month follow-up

• Comparison of Change in TBI Quality of Life Scale (TBI-QOL) Subtest Scores from Baseline to Post-intervention

  Baseline to post-intervention, within 10 working days of the final rTMS session

Study Arms (3)

Arm 1

EXPERIMENTAL

Active rTMS/Individualized Connectome Targeting (ICT)

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Arm 2

EXPERIMENTAL

Active rTMS/resting state functional MRI (rsfMRI)-based targeting

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Arm 3

SHAM COMPARATOR

Sham rTMS

Device: Sham rTMS

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Active rTMS

Arm 1; Arm 2

Sham rTMS DEVICE

Sham comparator to active rTMS

Arm 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-55 at the time of consent. Older individuals will not be enrolled in this initial trial for reasons of safety and expected reduced efficacy.
• Current or former US military service member eligible for care at a Military Treatment Facility (MTF) or Veterans Administration Medical Center (VAMC.)
• Able to provide written, informed consent in English .
• Self-reported or medically diagnosed history of concussion (synonymous with "mild TBI.") \>6 months, but \<26 years prior to consent, defined based on the DoD/VA definition:
• Positive Loss of Consciousness of \<30 minutes as confirmed by the TBI Screener and/or medical records and/or;
• Positive Alteration of Consciousness of \<24 hours as confirmed by the TBI Screener and/or medical records and/or;
• Positive Post-traumatic Amnesia of 0 to 1 day as confirmed by the TBI Screener and/or medical records.
• Note: Neuroimaging data or documentation from medical records is not required.
• Baseline MADRS \>13 at the time of screening indicating at least mild-moderate depressive symptoms.
• Maintained a steady psychotropic medication regimen for six weeks and a steady behavioral therapy regimen for twelve weeks prior to enrollment in the study.
• Female participants with child-bearing potential must agree to use an effective method of birth control during the course of the study.
• Under the care of a primary care and/or behavioral health provider.

You may not qualify if:

• Elevated risk of seizures at the time of rTMS including any of the following:
• History of unprovoked seizures.
• History of seizure within 24 hours of sustaining a concussion(s) or other head injury regardless of whether it was determined to have been related to concussion.
• Family history of two or more unprovoked seizures in a first degree relative (parent, sibling, or child).
• History of Moderate, Severe, or Penetrating TBI based on TBI Screener and/or medical records.
• Intracranial lesion (such as intracranial tumor or intraparenchymal hemorrhage) that, in the opinion of the investigators, would increase seizure risk.
• Currently taking medication or other substances (such as tricyclic antidepressants or neuroleptics) that, in the opinion of the investigator, lowers the seizure threshold.
• Contraindications to awake 3T MRI without contrast at the time of the Baseline MRI according to site radiology department criteria.
• Severe claustrophobia interfering with medication/sedation-free 3T closed-bore MRI.
• Intracranial lesion that would produce an artifact that would compromise the integrity of rsfMRI data.
• History of severe or recent uncontrolled heart disease.
• Presence of a cardiac pacemaker or intracardiac lines.
• Any implant, prosthesis or other permanent alteration of the body (such as implanted neurostimulators and medication pumps) that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data.
• Presence of rapidly progressive illnesses such as late-stage cancer, neurodegenerative conditions, major organ failure, etc.
• History of Bipolar Disorder or Schizophrenia Spectrum Disorders.

Sponsors & Collaborators

• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• Uniformed Services University of the Health Sciences: collaborator
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (3)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

RECRUITING

William Beaumont Army Medical Center

Fort Bliss, Texas, 79918, United States

RECRUITING

Alexander T. Augusta Military Medical Center

Fort Belvoir, Virginia, 22060, United States

RECRUITING

Related Publications (1)

• Oberman LM, Penafiel AI, Dieterich R, Phan CT, Chou YY, Pham DL, Adamson MM, Hines CE, Rezaee Z, Deng ZD, Pal H, Lisanby SH, Brody DL. Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods. Front Neurol. 2025 Jun 13;16:1605157. doi: 10.3389/fneur.2025.1605157. eCollection 2025.

  PMID: 40584527 DERIVED

MeSH Terms

Conditions

Depression; Brain Concussion

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• David L Brody, MD, PhD

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth N Diaz Nelson, MPH

CONTACT

832-671-9532; elizabeth.nelson.ctr@usuhs.edu

Study Design

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

Model Details: Bayesian-adaptive trial design

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: June 22, 2022
• Study Start: December 16, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: After study completion, data sets will be de-identified and shared with the repositories. De-identified data sets will be stored in the repositories indefinitely.
• Access Criteria: Access to FITBIR will follow FITBIR Access Criteria.

Locations

US (3)