尽管有证据表明有效的综合行为疗法可以治疗肥胖和抑郁症,治疗反应是高度可变的,潜在的神经生物学机制仍然未知。这妨碍了为了优化治疗精度和效力而识别机械目标的努力。在NIH行为变化科学(SOBC)研究网络内资助,两阶段ENGAGE研究项目应用了一种实验性精准医学方法来解决这一差距。第一阶段的研究重点是论证技术可行性,对综合行为疗法的反应的目标参与和潜在的神经机制。这种疗法结合了基于视频的行为减肥计划和解决问题的抑郁症疗法,随着抗抑郁药物的需要加强,其临床有效性在一项母体随机临床试验中得到证实.这里,我们描述了参与第2阶段(ENGAGE-2)研究协议,该协议以2种方式建立在第1阶段:(1)动机性访谈增强的试点测试,独立的综合行为疗法,主要是少数患者样本,和(2)先验定义的神经目标的评估,特别是在第1阶段表现出参与和延展性的负面影响(威胁和悲伤)回路,作为治疗结果的中介。此外,2期研究包括概念和方法上的扩展,以探索微生物组-肠道-大脑和系统免疫途径在肥胖和抑郁症的综合行为治疗中的作用。这份协议文件记录了概念化,ENGAGE-2中的设计和跨学科方法,可以为实验精准医学未来的临床和转化研究提供信息,用于行为改变和慢性病管理。试用注册:ClinicalTrials.gov#NCT03,841,682。
Despite evidence for effective integrated behavior therapy for treating comorbid obesity and depression, treatment response is highly variable and the underlying neurobiological mechanisms remain unknown. This hampers efforts to identify mechanistic targets in order to optimize treatment precision and potency. Funded within the NIH Science of Behavior Change (SOBC) Research Network, the 2-phased ENGAGE research project applies an experimental precision medicine approach to address this gap. The Phase 1
study focused on demonstrating technical feasibility, target engagement and potential neural mechanisms of responses to an integrated behavior therapy. This therapy combines a video-based behavioral weight loss program and problem-solving therapy for depression, with as-needed intensification of antidepressant medications, and its clinical effectiveness was demonstrated within a parent randomized clinical
trial. Here, we describe the ENGAGE Phase 2 (ENGAGE-2)
study protocol which builds on Phase 1 in 2 ways: (1) pilot testing of an motivational interviewing-enhanced, integrated behavior therapy in an independent, primarily minority patient sample, and (2) evaluation of a priori defined neural targets, specifically the negative affect (threat and sadness) circuits which demonstrated engagement and malleability in Phase 1, as mediators of therapeutic outcomes. Additionally, the Phase 2
study includes a conceptual and methodological extension to explore the role of microbiome-gut-brain and systemic immunological pathways in integrated behavioral treatment of obesity and depression. This protocol paper documents the conceptualization, design and the transdisciplinary methodologies in ENGAGE-2, which can inform future clinical and translational research in experimental precision medicine for behavior change and chronic disease management.
Trial registration: ClinicalTrials.gov #NCT 03,841,682.