Clinical trial NCT05426967: rTMS for Military TBI-related Depression
Official title: ADEPT: Adaptive Trial for the Treatment of Depressive Symptoms Associated With Concussion Using Repetitive Transcranial Magnetic Stimulation Protocols
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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)
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Uniformed Services University of the Health Sciences
name: Congressionally Directed Medical Research Programs
First posted: 2022-06-22
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Bayesian-adaptive trial design
Primary purpose: TREATMENT

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).

Detailed description: In United States Military personnel, rates of depression may increase after mild traumatic brain injury, or concussion. rTMS may hold a therapeutic potential for alleviating symptoms of depression after concussion. This study is a randomized, double-blind, Bayesian adaptive trial aimed at determining the safety, efficacy, and tolerability of individualized connectome targeted (ICT)-accelerated intermittent Theta Burst Stimulation (aiTBS) and scalp-targeted aiTBS for the treatment of depressive symptoms in a properly powered sample of current and former US military service members with a history of concussion.

Eligibility criteria: 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.)

Primary outcomes:
measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores in a Subgroup
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores from Baseline to 6-month follow-up
timeFrame: Baseline to 6 months
measure: Comparison of Treatment Response or Remission in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Duration of Remission of Depressive Symptoms in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
timeFrame: Follow-up Period, from 1-6 months after the final rTMS session
measure: Comparison of Frequency of Adverse Events
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
Secondary outcomes:
measure: Comparison of Change in Inventory of Depressive Symptomatology-Self Report (IDS-SR) Scores from Baseline to post-intervention
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in Symptoms of Major Depressive Disorder Scale (SMDDS) Scores from Baseline to Post-intervention
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in Inventory of Depressive Symptomatology-Self Report (IDS-SR) Scores from Baseline to 6-month follow-up
timeFrame: Baseline to 6-month follow-up
measure: Comparison of Change in Symptoms of Major Depressive Disorder Scale (SMDDS) Scores from Baseline to 6-month follow-up
timeFrame: Baseline to 6-month follow-up
measure: Comparison of Change in TBI Quality of Life Scale (TBI-QOL) Subtest Scores from Baseline to Post-intervention
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in TBI Quality of Life Scale (TBI-QOL) Subtest Scores from Baseline to 6-month follow-up
timeFrame: Baseline to 6-month follow-up
measure: Comparison of Change in PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to Post-intervention
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to 6-month Follow-up
timeFrame: Baseline to 6-month follow-up
measure: Compliance Assessment
timeFrame: Post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in rsfMRI Connectivity from Baseline to Post-intervention
timeFrame: Baseline to post-intervention, within 10 working days of the final rTMS session
measure: Comparison of Change in rsfMRI Connectivity from Baseline to 6-month Follow-up
timeFrame: Baseline to 6-month follow-up
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Fort Bliss
country: United States
facility: William Beaumont Army Medical Center
state: Texas
city: Fort Belvoir
country: United States
facility: Alexander T. Augusta Military Medical Center
state: Virginia
Study officials:
affiliation: Uniformed Services University of the Health Sciences
name: David L Brody, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: