Improving Weight Loss in Early Non-responders to Behavioral Treatment

项目总结/摘要 我的长期职业目标是成为一名独立的研究人员，开发有效的肥胖治疗方法， 将这些治疗方法与患者的特征相匹配。通过临床心理学的训练，我获得了 开发和提供肥胖症的行为治疗（BT），并进行随机对照 随机对照试验（RCTs），以测试其疗效。作为一名博士后研究员，我被介绍给肥胖药物治疗，但 在这方面的经验仍然有限。为了成功地发展肥胖精准医学的职业生涯，我 将需要额外的训练，在行为，生物学和药理学对体重的影响。的 我提议的K23奖将使我能够投入95%的精力来填补我的培训中的关键空白，并进行 这项研究将使我成为一名独立的肥胖治疗研究者。 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 可能影响体重减轻的能量平衡调节机制;以及3）使用药理学试剂， 改善体重减轻。我将通过接受导师的指导， 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查行为表型和神经内分泌来补充这些训练目标 生物标志物作为早期体重减轻的预测因子，并通过测试药物是否能增强患者的体重减轻， 对BT的早期反应并不理想参与者将完成对行为和 生物学特性，随后进行4周的BT。那些在磨合期内体重下降< 2.0%的人将 然后随机分配至另外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 24-对于BT反应不佳的患者，体重减轻一周。这个项目可以塑造最佳实践 并最终产生用于将治疗与患者匹配的算法 特色 宾夕法尼亚大学体重和饮食失调中心的环境设备齐全 与人员，资源和基础设施，以支持拟议的项目。我也会使用最先进的设备 课程，并在宾夕法尼亚大学的研讨会，以完成我的研究和培训目标。我的导师团队将由 博士托马斯瓦登（心理学教授），包括从博士培训。 和马修·海斯博士（营养学副教授） 神经科学）在能量平衡机制。这种全面的跨学科指导方法将 使我能够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， 在K23合同结束之前开发成功的R 01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.