Mentored Patient-Oriented Research on Adolescent Alcohol Misuse and Treatment

项目概要/摘要 这项 K24 职业中期研究和指导计划旨在为候选人提供受保护的时间 指导患者护理，针对青少年酒精滥用问题开展以患者为导向的研究 (POR) 并进行指导 成瘾科学转化研究的初级临床研究者。了解行为方式， 在受控实验室环境中测量的生理和神经认知测定可用于 提前了解药物如何影响现实世界中的饮酒需要临床和药物方面的专业知识 行为神经科学、心理生理学和临床试验方法。近二十年来，候选人 建立了一个富有成效且持续资助的 POR 项目，将理论驱动的假设转化为 临床前和人体实验室研究到现实世界的应用。拟议的综合计划将 提高候选人在 POR 中指导初级临床研究人员的能力，并增强他作为一名 独立临床科学家。该研究计划的重点是改善治疗方案 通过优化药物与行为干预相结合的方式来解决青少年酒精滥用问题 通过提供在以下方面指导初级科学家的工具来实现指导目标：i) 酒精使用机制 疾病（AUD）发病机制和治疗效果，ii）临床试验方法，iii）生态瞬时 评估 (EMA) 和心理生理学研究方法，以及 iv) 负责任行为培训 研究。候选人的目标是进一步开发和完善实验治疗方法（R01 AA007850），产生高质量的信息，为有关是否进一步开发新颖性的决策提供信息 治疗是有保证的。这项工作的重点是开发创新的人类实验室范例和相关 可靠预测真实药理和行为干预效果的方法 世界并为 AUD 病因学模型提供信息。该 K24 将支持综合试点数据的收集 神经行为疗法结合了一种有前途的新型药物，已被证明可以减少饮酒和 成人的渴望，以及治疗青少年 AUD 的金标准心理社会干预。 青春期是酒精使用障碍（AUD）发病的关键时期。通常饮酒 AUD 的患病率在 21 岁之前达到峰值。然而，尽管有临床需求， 对青少年的 AUD 治疗依赖于社会心理干预，但效果有限。一种潜在的方法 改善青少年酒精治疗的方法是加强现有的最佳心理社会干预措施 药物治疗。尽管 FDA 批准了四种药物来帮助治疗成人 AUD，但目前还没有药物被批准使用。 适合青少年使用的药物和针对青少年的对照临床试验几乎不存在。优化 青少年的治疗选择需要缩小药物开发研究的这一重要差距。

PROJECT SUMMARY/ABSTRACT This K24 midcareer research and mentoring program aims to provide the candidate with protected time from direct patient care to conduct patient-oriented research (POR) on adolescent alcohol misuse and to mentor junior clinical investigators in translational research in addiction science. Understanding how behavioral, physiological, and neurocognitive assays measured in controlled laboratory settings can be leveraged to advance knowledge of how medications impact alcohol use in the real world requires expertise in clinical and behavioral neuroscience, psychophysiology, and clinical trials methods. For nearly two decades, the candidate has built a productive and continuously funded POR program that translates theory-driven hypotheses from preclinical and human laboratory research to real world applications. The proposed integrated plan will facilitate the candidate’s ability to mentor junior clinical investigators in POR and augment his capabilities as an independent clinician scientist. The research plan, which focuses on improving treatment options for adolescent alcohol misuse by optimizing ways to combine medications with behavioral interventions, dovetails the mentoring goals by providing a vehicle for mentoring junior scientists in: i) mechanisms of alcohol use disorder (AUD) pathogenesis and treatment effects, ii) clinical trial methods, iii) ecological momentary assessment (EMA) and psychophysiological research approaches, and iv) training in the responsible conduct of research. The candidate’s goal is to further develop and refine an experimental therapeutics approach (R01 AA007850) that yields high quality information to inform decisions about whether further development of novel treatments is warranted. This work centers on developing innovative human laboratory paradigms and related methods that reliably predict the efficacy of novel pharmacological and behavioral interventions in the real world and inform models of AUD etiology. This K24 will support the collection of pilot data for an integrative neurobehavioral therapy that combines a promising novel medication, shown to reduce alcohol use and craving in adults, with a gold standard psychosocial intervention for treating AUD among adolescents. Adolescence is a critical period for the pathogenesis of alcohol use disorder (AUD). Alcohol use typically begins during adolescence and prevalence rates for AUD peak before age 21. Yet, despite clinical demand, AUD treatments for youth rely on psychosocial interventions that yield only modest benefits. One potential way to improve adolescent alcohol treatment is to augment the best available psychosocial interventions with pharmacotherapy. Although the FDA approved four medications to help treat AUD in adults, no medication is indicated for adolescent use and controlled clinical trials with teenagers are almost nonexistent. Optimizing treatment options for youth will require closing this important gap in medication development research.