Frequency and E-field Enhancement of iTBS for Depression (FREED)

iTBS 的频率和电场增强治疗抑郁症（免费）

基本信息

批准号：
10645423
负责人：
Zafiris J. Daskalakis
金额：
$ 80.42万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10645423
关键词：
Anatomy Biological Brain Clinical Clinical Trials Clinical assessments Coupled Coupling Data Diagnosis Disease Disease remission Dose Double-Blind Method Effectiveness Electroencephalography Ensure Frequencies Goals Individual Investigation Left Link Location Major Depressive Disorder Measures Mental Depression Methods Modeling Moods Neuronal Plasticity Outcome Parietal Patients Pattern Performance Phase Physiologic pulse Population Prefrontal Cortex Randomized Randomized, Controlled Trials Reporting Research Resistance Rest Safety Severities Short-Term Memory Site Testing Time Treatment Cost Treatment Efficacy arm clinical efficacy clinical practice cognitive function comparative efficacy cost effectiveness depressive symptoms effective therapy electric field improved individual patient individualized medicine interest neuroimaging novel novel strategies programs repetitive transcranial magnetic stimulation response societal costs symptomatic improvement treatment response treatment-resistant depression trial comparing

项目摘要

Abstract Treatment resistant depression (TRD) is present in about 2.5 percent of the population and is associated with considerable personal suffering and societal costs. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. However, while there is convincing evidence for the effectiveness of rTMS treatment, the overall remission rate achieved in patients is typically considerably less than 50%. Coupled with the fact that a course of rTMS takes considerable time to administer (up to 6 weeks), this limited efficacy substantially impacts clinical utility. Intermittent theta burst stimulation (iTBS) is a new form of TMS that involves the patterned application of stimulation pulses in both the theta and gamma frequencies. iTBS has recently been shown to be non-inferior to standard rTMS but can be applied in a dramatically shorter time, typically three minutes per day compared to 20-40 minutes. However, the use of iTBS has not been shown to enhance overall treatment efficacy compared to rTMS. Several methods are under investigation to try to improve the efficacy of iTBS treatment, in part through the individualization of treatment parameters. In this study, individualization of iTBS will include frequency and location optimization. Frequency individualization involves stimulating at each patient’s endogenous brain rhythms derived from theta- gamma coupling during a working memory task. Our findings suggest that such frequency individualization of iTBS produces greater effects on neuroplasticity, cognitive function, and mood enhancement in healthy subjects. Next, we have developed methods to individualize coil placement using electric field (E-field) modelling to limit anatomic variability and maximize dosing for each patient. We will aim to individually target the TMS e-field to a specific cortical region corresponding to Talairach coordinate (–45, 45, 35) in the left dorsolateral prefrontal cortex (DLPFC). We also previously reported that targeting this region with rTMS produces superior efficacy compared to conventional targeting. We now propose to undertake a 2-phase program to determine if individualized iTBS based on frequency and E-field modelling will enhance its efficacy in patients with TRD. In the R61 phase of this application, we will test if this novel approach produces target engagement by randomizing 75 patients with TRD to a course of frequency and location individualized iTBS, location individualized iTBS only, or standard iTBS stimulation. We aim to establish whether individualized frequency/location iTBS produces a greater change in theta connectivity as a demonstration of its capacity to alter activity in relevant frontal–parietal circuitry. If this is established, we will have achieved our go-criterion and will request to proceed with the three- year R33 phase. During this phase, we will conduct a larger scale randomized controlled trial comparing individualized frequency/location iTBS to standard iTBS in 144 patients with TRD and compare the effects on both target engagement (fronto-parietal theta connectivity) and clinical outcomes (depression severity). The overall goal of this research is to develop a more effective form of iTBS treatment for patients with TRD.

抽象的大约 2.5% 的人口存在治疗抵抗性抑郁症 (TRD)，并且与重复经颅磁刺激 (rTMS) 是一种安全的方法，会带来相当大的个人痛苦和社会成本。 TRD 的有效治疗方法越来越多地应用于世界各地的临床实践。虽然有令人信服的证据证明 rTMS 治疗的有效性，但总体缓解率患者的这一比例通常远低于 50%，而且一个疗程的 rTMS 需要相当长的时间。给药时间（最多 6 周），这种有限的功效会严重影响间歇性 θ 爆发。刺激 (iTBS) 是 TMS 的一种新形式，涉及刺激脉冲的模式化应用 iTBS 频率最近已被证明不劣于标准 rTMS，但可以进行改进。与 20-40 分钟相比，应用时间大大缩短，通常为每天 3 分钟。与 rTMS 相比，iTBS 的使用尚未被证明可以提高总体治疗效果。正在研究尝试提高 iTBS 治疗的疗效，部分方法是通过个体化治疗在本研究中，iTBS 的个体化将包括频率和位置优化。频率个性化涉及刺激每个患者的内源性大脑节律，这些节律源自 theta- 我们的研究结果表明，工作记忆任务中的这种频率个体化。 iTBS 对健康受试者的神经可塑性、认知功能和情绪增强产生更大的影响。接下来，我们开发了使用电场 (E-field) 建模来个性化线圈放置的方法，以限制我们的目标是针对每位患者的解剖结构变异性和最大剂量进行个性化的 TMS 电场定位。对应于左背外侧前额叶 Talairach 坐标 (–45, 45, 35) 的特定皮质区域我们之前也报道过，利用 rTMS 靶向该区域可产生卓越的功效。与传统的目标定位相比，我们现在建议开展一个分两阶段的计划来确定是否可以。基于频率和电场建模的个体化 iTBS 将增强其对 TRD 患者的疗效。在该应用程序的 R61 阶段，我们将测试这种新颖的方法是否通过随机化产生目标参与度 75 名 TRD 患者接受了频率和位置个性化 iTBS 疗程，仅位置个性化 iTBS，我们的目标是确定个性化频率/位置 iTBS 是否会产生刺激。 θ 连接性发生更大变化，表明其改变相关额顶叶活动的能力如果这一点成立，我们将达到我们的标准，并将要求继续进行三项工作。今年R33阶段，我们将进行更大规模的随机对照试验进行比较。在 144 名 TRD 患者中进行个体化频率/位置 iTBS 与标准 iTBS 的比较，并比较其效果目标参与度（额顶叶θ连通性）和临床结果（抑郁严重程度）。这项研究的总体目标是为 TRD 患者开发一种更有效的 iTBS 治疗方法。