A Randomized Controlled Trial of Sequential Bilateral Accelerated Theta Burst Stimulation in Adolescents with Suicidal Ideation Associated with Major Depressive Disorder

对患有重度抑郁症相关自杀意念的青少年进行序贯双侧加速 Theta 爆发刺激的随机对照试验

• 批准号: 10463815
• 负责人: Paul E Croarkin
• 金额: $ 60.99万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463815
• 关键词: Acute; Address; Adolescent; Adopted; Aftercare; Base of the Brain; Bilateral; Biological Markers; Brain; Cause of Death; Clinic; Clinical; Clinical Research; Collaborations; Crisis Intervention; Data; Dose; Double-Blind Method; Electroencephalography; Electromyography; Electrophysiology (science); Emergency department visit; Feeling suicidal; Fostering; Hospitalization; Infrastructure; Intervention; Lead; Left; Major Depressive Disorder; Measures; Methodology; Outcome; Outcome Measure; Prefrontal Cortex; Prevention; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Research; Research Personnel; Risk Assessment; Severities; Suicide; Synaptic plasticity; Techniques; Teenagers; Therapeutic Trials; Transcranial magnetic stimulation; Treatment Protocols; United States; Work; arm; biomarker panel; child depression; clinical effect; clinical implementation; comparison group; comparison intervention; depressive symptoms; efficacy evaluation; follow-up; gamma-Aminobutyric Acid; ideation; improved; novel strategies; predictive marker; safety and feasibility; sham-controlled study; standard of care; suicidal behavior; suicidal risk; treatment duration; treatment trial; trial comparing

PROJECT SUMMARY/ABSTRACT Suicide is a leading cause of death in adolescents worldwide and a substantial public health problem in the United States. Despite prior efforts, outcomes related to suicide in adolescents are not improving over the years. Standard clinical and research approaches involve prevention efforts, risk assessment, crisis intervention, and psychotherapeutic techniques. Few prior studies have focused on developing brain-based treatments and biomarkers for active suicidal ideation in adolescents with depression. Conceptually, dysregulations in prefrontal cortex gamma-aminobutyric acid (GABA) inhibitory function could lead to reduced control of suicidal thoughts and behaviors in adolescents with depression. Transcranial magnetic stimulation (TMS) treatment protocols delivered to the prefrontal cortex modulate GABA inhibitory function, synaptic plasticity, and clinical symptoms of depression. Accelerated TMS protocols that deliver theta burst stimulation (TBS) dosing induce synaptic plasticity changes rapidly, modulate GABA function, have rapid-acting clinical effects, and overcome the many practical limitations of standard TMS. Prior research with a biomarker of GABA activity called long-interval cortical inhibition (LICI) demonstrates potential for clinical implementation to assess suicide risk and guide treatment interventions with TMS. Electromyography (EMG) measures of LICI are easily collected and have been studied extensively in adolescents. Measures of LICI with electroencephalography (EEG) may provide more precise and sophisticated measures of GABA inhibitory function. However, there are methodologic challenges with the use of EEG for LICI measures and no prior data in adolescents with depression. This study is a randomized, double-blind, sham-controlled trial of sequential bilateral accelerated TBS (aTBS) for suicidal ideation in adolescents with major depressive disorder (MDD). All subjects (in both arms) will concurrently receive standard of care treatment. Three TBS sessions will be administered daily for 10 days (5 days per week) for a total of 30 sessions. During each TBS session, continuous TBS is first delivered to the right dorsolateral prefrontal cortex and then intermittent TBS is delivered to the left dorsolateral prefrontal cortex. The proposed TBS parameters were adopted from prior work in adolescents. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. This study will examine the safety, feasibility, and clinical effects of sequential bilateral aTBS. The primary clinical outcome will be assessed over 10 days of treatment and the following year with the Columbia Suicide Severity Rating Scale severity of ideation subscale. The research team will collect pre- and post- treatment LICI measures with EMG to assess suicide risk and guide treatment with TBS protocols. Concurrent LICI measures with EEG will address an exploratory aim to further develop and refine LICI biomarkers. Existing infrastructure and collaborations will foster the rapid clinical implementation of sequential bilateral aTBS and cortical inhibition biomarkers.

项目总结/摘要 自杀是全世界青少年死亡的主要原因，也是世界上一个重大的公共卫生问题。 美国的尽管先前的努力，与青少年自杀有关的结果并没有在2009年有所改善。 年标准临床和研究方法涉及预防工作、风险评估、危机 干预和心理治疗技术。以前很少有研究集中在开发基于大脑的 抑郁症青少年主动自杀意念的治疗和生物标志物。从概念上讲， 前额叶皮层γ-氨基丁酸（GABA）抑制功能的失调可能导致减少 控制青少年抑郁症患者的自杀想法和行为。经颅磁刺激 (TMS)传递到前额皮质的治疗方案调节GABA抑制功能、突触 可塑性和抑郁症的临床症状。提供θ波爆发刺激的加速TMS方案 (TBS)剂量诱导突触可塑性变化迅速，调节GABA功能，具有速效临床 有效地克服了标准TMS的许多实际局限性。先前研究的生物标志物为 GABA活动称为长间隔皮层抑制（LICI），证明了临床实施的潜力， 评估自杀风险并指导TMS治疗干预。LICI的肌电图（EMG）测量 很容易收集，并在青少年中进行了广泛的研究。LICI的措施， 脑电图（EEG）可以提供更精确和复杂的措施，GABA抑制 功能然而，使用EEG进行LICI测量存在方法学挑战，并且没有先前的数据 青少年抑郁症患者本研究是一项随机、双盲、假手术对照的序贯试验， 双侧加速TBS（aTBS）在青少年重度抑郁症（MDD）自杀意念中的应用。所有 受试者（两组）将同时接受标准护理治疗。三个TBS会议将在 每天给药10天（每周5天），共30个疗程。在每次TBS会话期间， 首先将连续TBS递送到右背外侧前额叶皮层，然后将间歇TBS递送到右背外侧前额叶皮层。 传递到左背外侧前额叶皮层。建议的TBS参数采用了之前工作中的参数 在青少年中。对照组将接受每日3次的双侧假TBS治疗，持续10天。 天本研究将检查序贯双侧aTBS的安全性、可行性和临床效果。的 主要临床结局将在治疗10天内和下一年用哥伦比亚 自杀严重程度评定量表意念严重程度子量表。研究小组将收集前和后- 治疗LICI措施与肌电图评估自杀风险和指导治疗与TBS协议。并发 采用EEG测量LICI将解决进一步开发和完善LICI生物标志物的探索性目标。 现有的基础设施和合作将促进快速临床实施顺序双边 aTBS和皮质抑制生物标志物。