Mentored Patient-Oriented Research on Adolescent Alcohol Misuse and Treatment

项目摘要/摘要 这项K24职业生涯中期研究和指导计划旨在为应聘者提供保护时间，使其 指导患者护理，对青少年酒精滥用进行以患者为中心的研究(POR)并指导 成瘾科学翻译研究的初级临床研究人员。理解行为如何， 在受控实验室环境中测量的生理和神经认知分析可用于 对药物如何影响现实世界中的酒精使用的高级知识需要临床和 行为神经科学、心理生理学和临床试验方法。近二十年来，这位候选人 建立了一个富有成效且持续资助的POR计划，将理论驱动的假设从 临床前和人体实验室研究在现实世界中的应用。拟议的综合计划将 促进候选人指导初级临床研究人员的能力，并增强其作为 独立的临床医生科学家。这项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滥用青少年酒精，吻合 指导目标是通过提供一种工具来指导初级科学家：i)酒精使用机制 障碍(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，以及四)负责任的行为培训 研究的成果。候选人的目标是进一步发展和改进实验性治疗方法(R01 AA007850)，产生高质量的信息，为决定是否进一步开发小说提供信息 治疗是有必要的。这项工作的中心是开发创新的人体实验室范例和相关 可靠地预测新的药物和行为干预在实际中的疗效的方法 世界和告知澳大利亚疾病病因学的模型。这款K24将支持为集成的 神经行为疗法结合了一种有希望的新型药物，显示出减少酒精使用和 成人中的渴求，以及治疗青少年AUD的黄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。典型的饮酒方式 从青春期开始，AUD患病率在21岁之前达到顶峰。然而，尽管有临床需求， 对青少年的非酒精性精神障碍治疗依赖于心理社会干预，而这些干预措施只能产生不大的益处。一种潜在的方式 改善青少年酗酒治疗就是通过增加最好的心理社会干预 药物疗法。尽管FDA批准了四种药物来帮助治疗成人AUD，但没有一种药物是 用于青少年的药物和青少年对照临床试验几乎不存在。优化 年轻人的治疗选择将需要缩小药物开发研究方面的这一重要差距。

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.