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.

抑郁症是全球残疾的主要原因，是最普遍的神经精神疾病之一 脊髓损伤（SCI）。 SCI后抑郁症的负担很大，因为它与较高的 成本，较低的生活质量和较短的生存时间。治疗抑郁症可能很复杂，但至关重要。 重复的经颅磁刺激（RTMS）是一种非侵入性大脑刺激，是FDA批准的 在整个退伍军人事务（VA）卫生系统中使用的抑郁症的治疗选择。但是，不 已发表的研究检查了RTMS对SCI后抑郁症的有效性。更新的临床 脊髓医学的实践指南，用于管理心理健康疾病的管理（2020） 瘫痪的美国退伍军人明确建议未来的研究检查SCI人群中的RTMS。 在SCI后为抑郁症施用RTM的关键挑战是给药。目前，静止电机 阈值是右绑架者Pollicis Brevis的运动响应，用于剂量rtms。超过一半的科幻 人口不完整或完全四倍体，表明上肢的某种程度[（UE）]受损。 因此，如果使用当前的RTMS剂量参数，则可以得出结论，超过一半的SCI种群可以 被排除在接受抑郁症的RTMS之外或可能会接受不当剂量，从而影响干预措施 安全性和有效性。 [这项研究专门解决了治疗抑郁症的当前局限性 - SCI使用RTMS和WILL：（1）确定RTMS的目标电场（E-Field）； （2）评估小说 方法，反向计算电子场建模，以确定RTMS剂量以治疗抑郁症 有科幻的人； （3）使用反向计算电子场建模进行剂量的试验临床试验 SCI后抑郁症的RTM； （4）为申请人提供适当的培训环境 发展成为独立的VA研究员； （5）生成必要的试点数据以支持未来 va优异奖应用程序。]电子场建模是一个计算模型，该模型说明了TMS线圈类型， 电路和放置，通过T1和T2加权磁共振图像获得的单个解剖结构， 组织类型之间的电导率差异。 [首先，使用现有的试验数据，电子场建模将用于 确定目标电子场剂量用于用RTM治疗抑郁症。]接下来，二十四名SCI和 抑郁症将被随机分配，以接受6周的RTMS治疗，使用反向计量E- 现场建模（n = 18）或假治疗（n = 6）。我们将研究治疗对 使用汉密尔顿评级量表的抑郁症状用于抑郁。通过反向计算确定的剂量 电子场建模将与FDA批准的参数结合使用：10 Hz时3,000脉冲/会话，5 天/周6周。研究结果将包括抑郁症状的变化，生活质量[（QOL）]， 和参与。在奖励期内，申请人将利用拉尔夫可用的资源 H. Johnson VA医疗中心及其附属学院，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 P2 CHD086844）。通过使用 申请人的这些资源和动手培训旨在开发必要的 对数据获取，分析和解释神经生物学变量，成像， 和电子场建模。该CDA-2应用的总体目标是将候选人暴露于富裕的当地人 SCI恢复研究的环境，为发展成为独立VA的基础 研究人员研究抑郁症SCI后抑郁症和可行的治疗方法改善的影响 退伍军人的生活和康复结果。拟议的培训计划将增强候选人的 了解神经调节，神经精神疾病以及神经居住的设计和交付 试验。生成的数据将告知开发有关神经调节的其他干预措施 在SCI和其他患有UE运动障碍的患者人群之后，改善功能和QOL。