Evaluating a Novel Method to Determine the rTMS Dose Needed for Treating Depression After Spinal Cord Injury

评估一种确定治疗脊髓损伤后抑郁症所需 rTMS 剂量的新方法

• 批准号: 10539436
• 负责人: Catherine Jefferson VanDerwerker
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-01 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10539436
• 关键词: Address; Amputees; Anatomy; Antidepressive Agents; Award; Caregivers; Clinical; Clinical Practice Guideline; Clinical Trials; Clinical effectiveness; Computer Models; Data; Data Analyses; Dedications; Development; Dose; Effectiveness; Eligibility Determination; Enrollment; Environment; Evidence based treatment; Exclusion; Exposure to; FDA approved; Family; Foundations; Funding; Future; General Population; Goals; Hamilton Rating Scale for Depression; Health system; Image; Impairment; Individual; Institution; Intervention; Left; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Medical; Medical center; Medicine; Mental Depression; Mental disorders; Mentors; Methods; Modeling; Motor; Neurobiology; Outcome Measure; Outcome Study; Paralysed; Patient Outcomes Assessments; Physiologic pulse; Placebos; Population; Prefrontal Cortex; Prevalence; Protocols documentation; Publishing; Quadriplegia; Quality of life; Randomized; Recommendation; Recovery; Rehabilitation Outcome; Rehabilitation therapy; Reporting; Research; Research Personnel; Resources; Rest; Safety; Sampling; South Carolina; Spinal Cord; Spinal cord injury; Techniques; Thumb structure; Time; Tissues; Training; Transcranial magnetic stimulation; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Update; Upper Extremity; Veterans; Veterans Health Administration; Work; antidepressant effect; arm; associated symptom; cohort; comorbid depression; cost; data acquisition; depressive symptoms; design; disability; dose individualization; effective therapy; effectiveness evaluation; electric field; evidence based guidelines; functional improvement; hand dysfunction; health care service utilization; improved; injury recovery; mortality; motor impairment; multi-site trial; neurological rehabilitation; neuropsychiatric disorder; neuropsychiatry; neuroregulation; noninvasive brain stimulation; novel; patient population; placebo group; primary outcome; psychosocial; rehabilitative care; repetitive transcranial magnetic stimulation; response; skills; treatment effect; trial planning

Depression is a leading cause of disability worldwide and is one of the most prevalent neuropsychiatric disorders following spinal cord injury (SCI). The burden of depression post-SCI is significant, as it is associated with higher cost, lower quality of life, and shorter survival time. Treating depression can be complicated, but it is vital. Repetitive transcranial magnetic stimulation (rTMS), a type of non-invasive brain stimulation, is an FDA-approved treatment option for depression that is utilized throughout the Veterans Affairs (VA) health system. However, no published studies have examined the effectiveness of rTMS for depression post-SCI. The updated Clinical Practice Guidelines for Spinal Cord Medicine for the Management of Mental Health Disorders (2020) by the Paralyzed Veterans of America recommends explicitly that future research examines rTMS in the SCI population. The critical challenge of administering rTMS for depression post-SCI is dosing. Currently, the resting motor threshold, a motor response of the right abductor pollicis brevis, is used to dose rTMS. Over half of the SCI population has incomplete or complete tetraplegia, indicating some degree of upper extremity [(UE)] impairment. Thus, if using current rTMS dosing parameters, it is plausible to conclude that over half the SCI population could be excluded from receiving rTMS for depression or may receive an improper dose, impacting the intervention's safety and effectiveness. [This study specifically addresses current limitations in treating depression post- SCI using rTMS and will: (1) identify the target electric-field (e-field) for rTMS; (2) evaluate a novel method, reverse-calculation e-field modeling, to determine the rTMS dose to treat depression in individuals with SCI; (3) conduct a pilot clinical trial using reverse-calculation e-field modeling to dose rTMS for depression post-SCI; (4) provide the appropriate training environment for the applicant to develop into an independent VA researcher; and (5) generate the necessary pilot data to support a future VA Merit Award application.] E-field modeling is a computational model that accounts for the TMS coil type, circuitry and placement, individual anatomy obtained through T1 and T2- weighted magnetic resonance images, and conductivity variance between tissue types. [First, using existing trial data, e-field modeling will be used to determine the target e-field dose for treating depression with rTMS.] Next, twenty-four individuals with SCI and depression will be randomized to receive either 6-weeks of rTMS treatment dosed using reverse-calculation e- field modeling (n=18) or sham treatment (n=6). We will examine the between-group effects of treatment on depressive symptoms using the Hamilton Rating Scale for Depression. The dose identified by reverse-calculation e-field modeling will be used in combination with FDA-approved parameters: 3,000 pulses/session at 10 Hz, 5 days/week for 6 weeks. Study outcomes will include changes in depressive symptoms, quality of life [(QOL)], and participation. During the award period, the applicant will capitalize on resources available through the Ralph H. Johnson VA Medical Center and its affiliated academic institution, Medical University of South Carolina. One primary example is the National Center for Neuromodulation for Rehabilitation (NIH P2 CHD086844). By utilizing these resources and hands-on training from renowned local experts, the applicant aims to develop the requisite skills and understanding of data acquisition, analysis, and interpretation of neurobiological variables, imaging, and e-field modeling. The overall goal of this CDA-2 application is to expose the candidate to a rich local environment for SCI recovery research, providing the foundation for developing into an independent VA researcher studying the effects of and viable treatment options for depression post-SCI to improve the lives and rehabilitation outcomes of Veterans. The proposed training plan will enhance the candidate's understanding of neuromodulation, neuropsychiatric disorders, and the design and delivery of neurorehabilitation trials. The data generated will inform the development of additional interventions focused on neuromodulation to improve function and QOL for individuals following SCI and other patient populations with UE motor impairment.

抑郁症是世界范围内导致残疾的主要原因，也是最常见的神经精神疾病之一 脊髓损伤（SCI）。SCI后抑郁的负担是显著的，因为它与更高的 成本、生活质量降低和生存时间缩短。治疗抑郁症可能很复杂，但至关重要。 重复经颅磁刺激（rTMS），一种非侵入性脑刺激，是FDA批准的 抑郁症的治疗选择，这是整个退伍军人事务部（VA）卫生系统使用。但没有 已发表的研究已经检查了rTMS对SCI后抑郁症的有效性。更新的临床 脊髓医学管理心理健康疾病实践指南（2020） Paralyzed Veterans of America明确建议未来的研究在SCI人群中检查rTMS。 rTMS治疗SCI后抑郁症的关键挑战是剂量。目前，静止电机 阈值，右拇短展肌的运动反应，用于剂量rTMS。超过一半的SCI 人群有不完全或完全性四肢瘫痪，表明一定程度的上肢[（UE）]损伤。 因此，如果使用当前的rTMS剂量参数，可以合理地得出结论，超过一半的SCI人群可能 被排除接受rTMS治疗抑郁症或可能接受不适当的剂量，影响干预的 安全性和有效性。[This这项研究专门针对目前治疗抑郁症的局限性， SCI使用rTMS，将：（1）确定rTMS的目标电场（e场）;（2）评估新的 方法，反向计算电场建模，以确定治疗抑郁症的rTMS剂量， SCI患者;（3）使用反向计算电场模型进行试点临床试验，以剂量 为SCI后抑郁症提供rTMS;（4）为申请人提供适当的培训环境， 发展成为一个独立的VA研究人员;（5）生成必要的试点数据，以支持未来 VA优异奖申请。]电场建模是考虑TMS线圈类型的计算模型， 电路和放置，通过T1和T2加权磁共振图像获得的个体解剖结构， 以及组织类型之间的电导率差异。[首先，使用现有的试验数据，将使用电场建模来 确定用rTMS治疗抑郁症的目标电场剂量。]接下来，24名SCI患者和 抑郁症患者将随机接受6周rTMS治疗，使用反向计算法进行给药， 场模型（n=18）或假处理（n=6）。我们将研究治疗对 使用汉密尔顿抑郁量表评估抑郁症状。通过反向计算确定的剂量 电场建模将与FDA批准的参数结合使用：3，000个脉冲/会话，10 Hz，5 天/周，持续6周。研究结果将包括抑郁症状、生活质量[（QOL）]、 和参与。在奖励期间，申请人将利用拉尔夫 H.约翰逊VA医疗中心及其附属学术机构，南卡罗来纳州医科大学。一 主要的例子是国家康复神经调节中心（NIH P2CHD 086844）。通过利用 这些资源和来自当地知名专家的实践培训，申请人旨在开发所需的 技能和数据采集，分析和神经生物学变量的解释，成像， 和电场建模。此CDA-2应用程序的总体目标是将候选人展示给富有的当地人 SCI恢复研究的环境，为发展成为独立的VA提供基础 研究人员研究SCI后抑郁症的影响和可行的治疗方案，以改善 退伍军人的生活和康复结果。拟议的培训计划将提高候选人的 了解神经调节，神经精神疾病，以及神经康复的设计和提供 审判生成的数据将为开发专注于神经调节的其他干预措施提供信息， 改善SCI患者和其他UE运动障碍患者的功能和生活质量。