Development of Low-Intensity Focused Ultrasound for Post Traumatic Brain Injury Depression
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of repeated sgACC-targeted LIFU stimulation in adult Veterans with PTD.
研究概览
简要总结
The goal of this clinical trial is to learn about evaluate the safety, tolerability, and feasibility of MRI-guided LIFU targeting the sgACC in Veterans with post-traumatic brain injury depression. The main questions it aims to answer are:
- the safety, tolerability, and feasibility of MRI-guided LIFU.
- Evaluate preliminary antidepressant efficacy.
- Characterize target engagement using multimodal neuroimaging and electrophysiology.
- Identify imaging and electrophysiological biomarkers that predict treatment response.
- Generate preliminary effect size estimates to support future multicenter clinical trials.
详细描述
The study is a single-site, randomized (3:2 to active LIFU or sham), rater- and participant-blinded mechanistic study of MRI-guided low-intensity focused ultrasound (LI-FUS) targeting the subgenual anterior cingulate cortex (sgACC) in adult Veterans with post traumatic brain injury depression (PTD). The purpose of this study is to evaluate the safety and tolerability of repeated sgACC-targeted LI-FUS stimulation in adult Veterans with PTD. To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LI-FUS in adult Veterans with PTD. To characterize the relationship between delivered LI-FUS dose and clinical response in adult Veterans with PTD. To characterize changes in neuroimaging and electrophysiologic measures associated with LI-FUS, including fMRI- and EEG-based indices of target engagement and network modulation, in adult Veterans with PTD. (b) To evaluate whether baseline fMRI and EEG features predict clinical response to LI-FUS in adult Veterans with PTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
The rater and participant will be blinded. Participants will be randomized 3:2 to Active LIFU or sham delivered.
入排标准
- 年龄范围
- 22 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult Veteran, male or female, 22 to 55 years of age at the time of screening.
- •Able to read, understand, and provide written, dated informed consent before initiation of formal study screening procedures. A brief IRB-approved telephone pre-screen may be conducted prior to written informed consent as described in Section 8.
- •Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and LIFU interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- •History of non-penetrating mild to moderate TBI confirmed by medical records and adjudicated by the study investigator using established TBI criteria (e.g., ACRM/VA-DoD criteria). If contemporaneous records are incomplete, a structured lifetime TBI interview may be used to support classification.
- •The TBI must have occurred at least 3 months before the occurrence of depression
- •Current depressive disorder defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- •Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM3).
- •MADRS score of ≥20 at screening.
- •Total duration of current depressive episode is less than 2 years
- •LIFU naive.
- •Access to ongoing psychiatric care before and after completion of the study.
- •The dose of the primary antidepressant medication must be stable for 6 weeks prior to baseline , and participants must agree to continue at this dose throughout the study period.
- •In good general health, as evidenced by medical history.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to baseline and agreement to use such a method during study participation.
- •Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration.
排除标准
- •Any lifetime DSM-5 depressive disorder or clinically significant depressive episode with onset prior to the qualifying index TBI, including major depressive disorder, persistent depressive disorder, or other specified/unspecified depressive disorder, or any antidepressant treatment initiated for depression prior to the index TBI.
- •Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
- •History of or current psychotic disorder or bipolar disorder
- •Severe borderline personality disorder.
- •Diagnosis of Intellectual Disability or Autism Spectrum Disorder
- •Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
- •Urine screening test positive for illicit substances
- •Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt (as defined by the C-SSRS) within the past one year
- •Cognitive impairment (defined as MoCA < 23)
- •10. Any history of ECT without meeting responder criteria
- •Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)
- •History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, or multiple sclerosis
- •Untreated or insufficiently treated endocrine disorder.
- •Contraindication to receiving LIFU
- •Contraindication to MRI (ferromagnetic metal in their body)
- •Treatment with another investigational drug or other intervention within the study period
- •Unstable symptoms between screening and baseline as defined by a > 30% change in MADRS-S score.
- •18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant
研究组 & 干预措施
Active Low-Intensity Focused Ultrasound (LIFU)
Participants receive active LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session
干预措施: Active Low-Intensity Focused Ultrasound (LIFU) (Device)
Sham Low-Intensity Focused Ultrasound (LIFU)
Participants receive sham LIFU over 5 consecutive treatment days, with 5 sessions per day and 20 minutes per session
干预措施: Sham Low-Intensity Focused Ultrasound (LIFU) (Other)
结局指标
主要结局
To evaluate the safety and tolerability of repeated sgACC-targeted LIFU stimulation in adult Veterans with PTD.
时间窗: Baseline, Treatment Days 1 through 5, 1-Week, 1-2:4-week follow up visits.
Cumulative incidence of treatment-emergent adverse events and serious adverse events.
次要结局
- To evaluate the preliminary antidepressant efficacy of repeated sgACC-targeted LIFU in adult Veterans with PTD.(Baseline, 1-week follow up, 4-week follow up)
研究者
Mahendra Bhati
Principal Investigator
Stanford University