Recruiting

RTMS

Sponsor:

Henry M. Jackson Foundation for the Advancement of Military Medicine

Code:

NCT05426967

Conditions

Depressive Symptoms

Mild Traumatic Brain Injury

Concussion

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham rTMS

Study Details

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

Study ID

NCT05426967

Start date

Dec 16, 2024

Status verified date

Apr, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Sep 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:

1. Positive Loss of Consciousness of <30 minutes as confirmed by the TBI Screener and/or medical records and/or;
2. Positive Alteration of Consciousness of <24 hours as confirmed by the TBI Screener and/or medical records and/or;
3. 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.

Exclusion Criteria:

  • Elevated risk of seizures at the time of rTMS including any of the following:

1. History of unprovoked seizures.
2. 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.
3. Family history of two or more unprovoked seizures in a first degree relative (parent, sibling, or child).
4. History of Moderate, Severe, or Penetrating TBI based on TBI Screener and/or medical records.
5. Intracranial lesion (such as intracranial tumor or intraparenchymal hemorrhage) that, in the opinion of the investigators, would increase seizure risk.
6. 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.
  • Current evidence of substance-induced mood disorder, active psychosis, or depression secondary to general medical illness other than TBI.
  • Severe or uncontrolled substance use.
  • Concomitant or lifetime history of receiving open-label TMS, due to issues preserving blinding.
  • Concomitant or recent history (within 12 weeks prior to enrollment) of receiving other neurostimulatory treatment, including but not limited to transcranial direct current (tDCS), transcranial alternating current (tACS), alpha stim, or electroconvulsive therapy.
  • Suicide attempt within six months prior to enrollment.
  • Right upper extremity amputation or other condition precluding left motor threshold calibration.
  • Unable to complete timeline of study (e.g., planned hospitalization partway through the study period.)
  • Prisoner, or other legally restricted freedom of movement and participation.
  • Any other considerations that, in the opinion of the investigators, may adversely affect participant safety, participation, or the scientific validity of the data being collected (e.g., erratic or unreliable responses, inconsistent communication, inability to remain on a steady neurotropic medication and/or behavioral therapy regimen over the course of the Randomization phase of the study.)

Study Design

Enrollment

198 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

Active rTMS/Individualized Connectome Targeting (ICT)

experimental: Arm 2

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

sham comparator: Arm 3

Sham rTMS

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS)

Active rTMS

Sham rTMS

Sham comparator to active rTMS

Primary outcome measure

  • Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to 6 months ]
  • Comparison of Treatment Response or Remission in Montgomery-Asberg Depression Rating Scale (MADRS) Scores [ Time Frame: 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 [ Time Frame: Follow-up Period, from 1-6 months after the final rTMS session ]
  • Comparison of Frequency of Adverse Events [ Time Frame: Baseline to post-intervention, within 10 working days of the final rTMS session ]

Central Contacts and Locations

Central contacts

Locations

VA Palo Alto Health Care System

Recruiting

Palo Alto, California, United States, 94304

Contacts

Rachel Dieterich

Rachel.Dieterich@va.gov

Principal Investigator:

Maheen M Adamson, PhD

William Beaumont Army Medical Center

Recruiting

Fort Bliss, Texas, United States, 79918

Contacts

Principal Investigator:

Jesse Wolfe, MD

Alexander T. Augusta Military Medical Center

Recruiting

Fort Belvoir, Virginia, United States, 22060

Principal Investigator:

Zachary J Craig, MD

More Information

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Last update posted

Apr 29, 2026

Last verified

Apr, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Henry M. Jackson Foundation for the Advancement of Military Medicine on 2026-04-29.