Mentored Patient-Oriented Research on Adolescent Alcohol Misuse and Treatment

项目概要/摘要 这个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，对青少年酒精滥用进行以患者为导向的研究（POR），并指导 成瘾科学转化研究的初级临床研究人员。了解行为， 在受控的实验室环境中测量的生理和神经认知测定可以被利用， 药物如何影响酒精使用在真实的世界的先进知识需要在临床和 行为神经科学、心理生理学和临床试验方法。近二十年来，候选人 已经建立了一个富有成效和持续资助的POR计划，将理论驱动的假设从 临床前和人类实验室研究到真实的世界应用。拟议的综合计划将 促进候选人在POR中指导初级临床研究者的能力，并增强其作为 独立临床科学家。该研究计划，重点是改善治疗方案， 通过优化联合收割机药物与行为干预相结合的方法， 通过提供一种工具，在以下方面指导青年科学家，实现指导目标：i）酒精使用的机制 疾病（AUD）的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）负责任行为的培训 的研究。候选人的目标是进一步发展和完善实验治疗方法（R 01 AA 007850），产生高质量的信息，以告知是否进一步开发新的 治疗是必要的。这项工作的中心是开发创新的人类实验室范式和相关的 可靠地预测新的药理学和行为干预在真实的 世界和通知模型的AUD病因。该K24将支持收集试点数据， 神经行为疗法结合了一种有前途的新型药物，显示可以减少酒精的使用， 成人的渴望，与青少年治疗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。酒精使用通常 在青春期开始，AUD的患病率在21岁之前达到峰值。然而，尽管临床需求， 青少年的AUD治疗依赖于社会心理干预，只能产生适度的益处。一种可能的方法是 改善青少年酒精治疗的方法是增加最好的心理社会干预， 药物治疗.虽然FDA批准了四种药物来帮助治疗成人AUD，但没有药物是有效的。 适用于青少年，几乎不存在青少年对照临床试验。优化 青年人的治疗选择将需要弥合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.