rTMS for Military TBI-related Depression

Официальное название

ADEPT: Adaptive Trial for the Treatment of Depressive Symptoms Associated With Concussion Using Repetitive Transcranial Magnetic Stimulation Protocols

Обзор

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).

Подробное описание

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.

Вмешательства

• Устройство Repetitive Transcranial Magnetic Stimulation (rTMS)
  Active rTMS
• Устройство Sham rTMS
  Sham comparator to active rTMS

Первичные конечные точки

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

Вторичные конечные точки (11)

• Comparison of Change in Inventory of Depressive Symptomatology-Self Report (IDS-SR) Scores from Baseline to post-intervention [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline to 6-month follow-up]
• Comparison of Change in TBI Quality of Life Scale (TBI-QOL) Subtest Scores from Baseline to Post-intervention [Срок оценки: Baseline to post-intervention, within 10 working days of the final rTMS session]
• Comparison of Change in TBI Quality of Life Scale (TBI-QOL) Subtest Scores from Baseline to 6-month follow-up [Срок оценки: Baseline to 6-month follow-up]
• Comparison of Change in PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to Post-intervention [Срок оценки: Baseline to post-intervention, within 10 working days of the final rTMS session]
• Comparison of Change in PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to 6-month Follow-up [Срок оценки: Baseline to 6-month follow-up]
• Compliance Assessment [Срок оценки: Post-intervention, within 10 working days of the final rTMS session]
• Comparison of Change in rsfMRI Connectivity from Baseline to Post-intervention [Срок оценки: Baseline to post-intervention, within 10 working days of the final rTMS session]
• Comparison of Change in rsfMRI Connectivity from Baseline to 6-month Follow-up [Срок оценки: Baseline to 6-month follow-up]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• 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.)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 3 центра

• VA Palo Alto Health Care System — Palo Alto
• William Beaumont Army Medical Center — Fort Bliss
• Alexander T. Augusta Military Medical Center — Fort Belvoir

Публикации

• 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

Идентификаторы

NCT: NCT05426967 · USUHS-2020-050

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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