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.

项目概要/摘要 自杀是全世界青少年死亡的主要原因，也是一个严重的公共卫生问题 美国。尽管之前做出了努力，但与青少年自杀相关的结果并没有改善 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。之前很少有研究关注开发基于大脑的 抑郁症青少年主动自杀意念的治疗方法和生物标志物。从概念上讲， 前额皮质γ-氨基丁酸（GABA）抑制功能失调可能导致 控制患有抑郁症的青少年的自杀想法和行为。经颅磁刺激 (TMS) 治疗方案传递到前额皮质调节 GABA 抑制功能、突触 可塑性和抑郁症的临床症状。提供 θ 爆发刺激的加速 TMS 协议 (TBS)给药诱导突触可塑性快速变化，调节GABA功能，临床起效快 效果，并克服标准 TMS 的许多实际限制。先前的生物标志物研究 称为长间隔皮质抑制 (LICI) 的 GABA 活性显示出临床实施的潜力 使用 TMS 评估自杀风险并指导治疗干预。 LICI 的肌电图 (EMG) 测量 很容易收集并已在青少年中进行了广泛研究。 LICI 的措施 脑电图 (EEG) 可以提供更精确、更复杂的 GABA 抑制测量 功能。然而，使用 EEG 进行 LICI 测量存在方法学上的挑战，并且没有先前的数据 患有抑郁症的青少年。本研究是一项随机、双盲、假对照序贯试验 双侧加速 TBS（aTBS）治疗重度抑郁症（MDD）青少年的自杀意念。全部 受试者（双臂）将同时接受标准护理治疗。 TBS 的三场会议将 每天进行 10 天（每周 5 天），总共 30 次。在每次 TBS 会议期间， 连续 TBS 首先传递到右侧背外侧前额叶皮层，然后间歇性 TBS 传递至左背外侧前额皮质。拟议的 TBS 参数是从之前的工作中采用的 在青少年中。对照组每天接受 3 次双侧假 TBS 治疗，持续 10 次。 天。本研究将检验序贯双侧 aTBS 的安全性、可行性和临床效果。这 主要临床结果将在 10 天的治疗期间以及接下来的一年中与 Columbia 进行评估 自杀严重程度评定量表 意念子量表的严重程度。研究小组将收集事前和事后 治疗 LICI 通过肌电图测量来评估自杀风险并指导 TBS 方案的治疗。并发 结合脑电图的 LICI 措施将实现进一步开发和完善 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顺序双边的快速临床实施 aTBS 和皮质抑制生物标志物。