Transcranial Magnetic Stimulation to Augment Exposure and Response Prevention for Pediatric OCD

经颅磁刺激可增加儿童强迫症的暴露和反应预防

• 批准号: 10722536
• 负责人: Kristen G Benito
• 金额: $ 122.47万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722536
• 关键词: 2 arm randomized control trial; Adult; Adverse event; Aftercare; Age; Area; Award; Behavior; Behavior Therapy; Behavioral; Brain; Childhood; Clinical; Clinical Trials; Compulsive Behavior; Corpus striatum structure; Data; Distress; Dorsal; Equilibrium; Exposure to; Fright; Functional Magnetic Resonance Imaging; Goals; Habits; Lateral; Left; Link; Masks; Measures; Mediating; Motor; Neurocognitive; Outcome; Phase; Prefrontal Cortex; Prevention; Public Health; Randomized; Regimen; Research; Rest; Safety; Sampling; Severities; Study models; Subgroup; Symptoms; Task Performances; Testing; Transcranial magnetic stimulation; Treatment outcome; Work; Youth; aged; arm; compulsion; design; efficacious treatment; flexibility; functional outcomes; improved; learning extinction; neural; neuromechanism; novel; repetitive transcranial magnetic stimulation; response; success; symptomatic improvement; treatment arm; treatment effect; treatment response; virtual; young adult

PROJECT SUMMARY Pediatric OCD is a public health problem and many remain symptomatic even after receiving efficacious treatments. The success of exposure and response prevention (ERP), a first-line behavioral treatment, depends on the ability to refrain from compulsions during exposure tasks. Improving this “therapy critical behavior” is a potentially important strategy for ERP augmentation. Repetitive transcranial magnetic stimulation (rTMS) can be leveraged to stimulate healthier functioning of brain circuits underlying therapy critical behaviors. The overall objective of this R61/R33 is to test whether augmenting ERP with rTMS over cortical nodes of select cortico-striatal circuits implicated in compulsivity can normalize connectivity and enhance response prevention in youth and young adults with OCD. The R61 phase of this project will use a masked RCT design to test whether ERP+TMS engages 1) hypothesized circuits involved in compulsivity and 2) observed response prevention during ERP exposure tasks. Youth ages 12-21 years with OCD will complete a full course of ERP plus randomly assigned TMS regimens of sham, iTBS to dlPFC, or cTBS to pSMA (n=20 per group). Milestones for the R61 phase are determination that at least one active rTMS condition a) changes RSFC in the hypothesized circuit within- and between-subjects and b) is safe and feasible. The R33 phase will use a masked RCT design to establish whether ERP+TMS engagement of the circuit and behavioral targets mediates changes in OCD symptom severity. A new sample of youth ages 12-21 with OCD will receive ERP plus either sham or active TMS stimulation, using the optimal TMS regimen identified in the R61 (n=30 per group). Exploratory analyses in both phases will examine whether neurocognitive task performance predicts symptom change, changes differentially by treatment arm, and corresponds with fMRI- measured metrics of cortico-striatal circuitry. At the end of this award, we will have determined whether rTMS is effective for improving compulsive behavior and functional connectivity in circuits underlying compulsivity, and whether these mediate change in clinical outcomes. If successful, we will be poised to conduct a large-scale trial of rTMS with ERP for pediatric OCD, including a confirmatory test of the linked mechanisms of both treatments. Ultimately, results from this line of research will inform understanding of neural mechanisms in rTMS and OCD and will provide a model for studying linked mechanisms in augmentation trials.

项目概要 儿童强迫症是一个公共卫生问题，许多人即使在接受有效的治疗后仍然有症状 治疗。暴露和反应预防（ERP）的成功，一线行为治疗， 取决于在暴露任务期间克制强迫的能力。改善这种“治疗关键 行为”是 ERP 增强的潜在重要策略。重复经颅磁刺激 （rTMS）可用于刺激治疗关键的大脑回路的更健康功能 行为。该 R61/R33 的总体目标是测试是否通过 rTMS 增强 ERP 与强迫症有关的特定皮质纹状体回路的节点可以使连接正常化并增强 患有强迫症的青少年和年轻人的反应预防。 该项目的R61阶段将使用屏蔽RCT设计来测试ERP+TMS是否起作用1) 假设的回路涉及强迫性和 2) 在 ERP 暴露期间观察到的反应预防 任务。 12-21 岁患有强迫症的青少年将完成完整的 ERP 课程以及随机分配的 TMS 假治疗方案、iTBS 至 dlPFC 或 cTBS 至 pSMA（每组 n = 20）。 R61 阶段的里程碑是 确定至少一个活跃的 rTMS 条件 a) 改变假设电路中的 RSFC，并且 受试者之间和 b) 是安全可行的。 R33 阶段将使用屏蔽 RCT 设计来确定 ERP+TMS 是否参与电路和 行为目标介导强迫症症状严重程度的变化。 12-21 岁患有强迫症的青少年的新样本 将接受 ERP 加上假刺激或主动 TMS 刺激，使用中确定的最佳 TMS 方案 R61（每组 n=30）。两个阶段的探索性分析将检查神经认知任务是否 表现可预测症状变化，治疗组的变化有所不同，并与功能磁共振成像相对应 皮质纹状体电路的测量指标。 在该奖项结束时，我们将确定 rTMS 是否能有效改善强迫行为 强迫性回路中的功能连接和功能连接，以及这些是否介导临床变化 结果。如果成功，我们将准备进行一项大规模的 rTMS 与 ERP 试验，用于治疗儿科强迫症， 包括对两种治疗方法的相关机制进行验证性测试。最终，这行的结果 研究将有助于理解 rTMS 和强迫症的神经机制，并将提供一个模型 研究增强试验中的相关机制。