ADEPT: Adaptive Trial for the Treatment of Depressive Symptoms Associated With Concussion Using Repetitive Transcranial Magnetic Stimulation Protocols
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 198
- 试验地点
- 6
- 主要终点
- Comparison of Frequency of Adverse Events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.)
结局指标
主要结局
Comparison of Frequency of Adverse Events
时间窗: Baseline to post-intervention, within 10 working days of the final rTMS session
Comparison of AEs between groups
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
时间窗: Baseline to post-intervention, within 10 working days of the final rTMS session
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.
Comparison of Duration of Remission of Depressive Symptoms in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
时间窗: Follow-up Period, from 1-6 months after the final rTMS session
Comparison of duration of remission of depressive symptoms in Montgomery-Asberg Depression Rating Scale (MADRS) Scores between groups assessed monthly during follow-up
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores from Baseline to 6-month follow-up
时间窗: Baseline to 6 months
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.
Comparison of Treatment Response or Remission in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
时间窗: Baseline to post-intervention, within 10 working days of the final rTMS session
Comparison of proportion of participants in each condition achieving treatment response ≥50% improvement in MADRS) or remission (MADRS ≤10)
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Scores in a Subgroup
时间窗: Baseline to post-intervention, within 10 working days of the final rTMS session
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.
次要结局
- 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)
- 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 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 PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to 6-month Follow-up(Baseline to 6-month follow-up)
- Compliance Assessment(Post-intervention, within 10 working days of the final rTMS session)
- Comparison of Change in rsfMRI Connectivity 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 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 6-month follow-up(Baseline to 6-month follow-up)
- Comparison of Change in PTSD Checklist for DSM-5 (PCL-5) Scores from Baseline to Post-intervention(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(Baseline to 6-month follow-up)
- Comparison of Change in rsfMRI Connectivity from Baseline to Post-intervention(Baseline to post-intervention, within 10 working days of the final rTMS session)