Improving Weight Loss in Early Non-responders to Behavioral Treatment

项目摘要/摘要 我的长期职业目标是成为一名独立的研究员，开发有效的肥胖治疗方法和 将这些治疗方法与患者的特征相匹配。通过我的临床心理学培训，我获得了 肥胖行为疗法(BTS)的发展和应用及随机对照研究 试验(RCT)以测试其疗效。作为一名博士后，我被介绍了肥胖症的药物疗法，但 在这方面的经验仍然有限。为了成功发展肥胖症的精准医学事业，我 将需要在行为、生物和药物对体重的影响方面进行额外的培训。这个 建议的K23奖项将使我能够将95%的精力用于填补我培训中的关键空白，并进行 这项研究将使我做好准备，成为肥胖治疗的独立调查者。 我的培训计划将通过增加我在三个关键领域的知识，为我的独立研究生涯做好准备： 1)与肥胖相关的行为表型及其客观测量方法；2)神经内分泌 可能影响减肥的能量平衡调节机制；以及3)使用药物来 改善减肥效果。我将通过接受导师的指导，参与实践，来实现这些目标 研究培训，并完成相关课程和研讨会。 我的研究项目将通过检测行为表型和神经内分泌来补充这些培训目标 生物标志物可作为早期体重减轻的预测指标，并通过测试药物是否增强患者的体重减轻 仅对Bt的早期反应不是最好的。参与者将完成行为和行为的初步评估 生物学特性，随后进行4周Bt。那些在磨合过程中减去初始体重2.0%的人将 然后随机分配到另外的24周：1)Bt+安慰剂；或2)Bt+药物(利拉鲁肽 3.0 mg)。我相信，低饱腹感将预示着BT早期减肥效果不佳，药物治疗将增强 对于对BT反应不佳的患者，24周的体重减轻。该项目可以形成最佳实践 建议肥胖治疗，并最终产生匹配治疗与患者的算法 特点。 宾夕法尼亚大学体重和饮食失调中心的环境条件很好 拥有支持拟议项目的人员、资源和基础设施。我还将参观最先进的设施， 在宾夕法尼亚大学完成我的研究和培训目标的课程作业和研讨会。我的导师团队将由 Thomas Wadden博士(心理学教授)，包括Tanja Kral博士(心理学副教授 护理)和Matthew Hayes博士(营养学副教授 神经科学)在能量平衡机制方面。这种全面的、跨学科指导的方法将 允许我获得对我的职业目标至关重要的领域的知识，实施拟议的研究计划，以及 在K23大奖结束之前，开发成功的R01应用程序。

PROJECT SUMMARY/ABSTRACT My long-term career goal is to be an independent investigator who develops effective obesity treatments and matches these treatments to patients' characteristics. Through my training in clinical psychology, I gained skills in the development and delivery of behavioral treatments (BTs) for obesity and in conducting randomized controlled trials (RCTs) to test their efficacy. As a postdoctoral fellow, I was then introduced to obesity pharmacotherapy, but still have limited experience in this area. In order to successfully develop a career in precision medicine for obesity, I will need additional training in behavioral, biological, and pharmacological influences on body weight. The proposed K23 award will allow me to devote 95% effort to filling critical gaps in my training and to conducting research that will prepare me to be an independent investigator in obesity treatment. My training plan will prepare me for an independent research career by increasing my knowledge in three key areas: 1) behavioral phenotypes associated with obesity and methods for their objective measurement; 2) neuroendocrine mechanisms of energy balance regulation that may impact weight loss; and 3) the use of pharmacologic agents to improve weight loss. I will accomplish these objectives by receiving guidance from mentors, engaging in hands-on research training, and completing relevant coursework and seminars. My research project will complement these training goals by examining behavioral phenotypes and neuroendocrine biomarkers as predictors of early weight loss and by testing whether medication enhances weight loss in patients with a suboptimal early response to BT alone. Participants will complete an initial assessment of behavioral and biological characteristics, followed by 4 weeks of BT. Those who lose < 2.0% of initial weight during the run-in will then be randomly assigned to an additional 24 weeks of: 1) BT plus placebo; or 2) BT plus medication (liraglutide 3.0 mg). I believe that low satiety will predict poor early weight loss with BT and that pharmacotherapy will enhance 24-week weight loss for patients with suboptimal response to BT. This project could shape best practice recommendations for obesity treatment and ultimately result in algorithms for matching treatments to patient characteristics. The environment at the Center for Weight and Eating Disorders at the University of Pennsylvania is well-equipped with staff, resources, and infrastructure to support the proposed project. I will also access state-of-the-art facilities, coursework, and seminars at Penn to complete my research and training goals. My mentorship team will be led by Dr. Thomas Wadden (Professor of Psychology) and includes training from Dr. Tanja Kral (Associate Professor of Nursing) in behavioral phenotypes of obesity and Dr. Matthew Hayes (Associate Professor of Nutritional Neuroscience) in mechanisms of energy balance. This comprehensive, interdisciplinary mentored approach will allow me to acquire knowledge in areas essential to my career goals, implement the proposed research plan, and develop a successful R01 application prior to the end of the K23 award.