Predictors of Weight Loss and Weight Loss Maintenance to Lifestyle Modification Therapy and Pharmacotherapy for Adolescents with Obesity

项目概要/摘要 神经行为特征有可能预测初始体重减轻和体重减轻的维持， 肥胖青少年对各种治疗方法的反应。然而，先前的研究受到限制， 严重依赖横截面分析和专注于浸入式干预（例如，住院 治疗），这是不广泛使用。识别临床上对神经行为反应的预测因子 适用的治疗方法将刺激新兴的精确医学领域取得必要的进展。建筑物对 受资助的随机比较有效性试验（R 01-DK 123273），本研究将前瞻性 检查神经行为预测的初始体重减轻反应和体重减轻维持 参与强化生活方式改变治疗（LMT）或低强度LMT+的肥胖青少年 使用胰高血糖素样肽-1受体激动剂（GLP 1-RA）Semaglutide进行药物管理。在 建议的研究我们将：1）确定青少年减肥反应的基线神经行为预测因子 2）对于在6个月时BMI降低>5%的参与者（即初始BMI降低>5%的参与者） 反应者），确定12岁时维持减肥的神经行为预测因素;以及3）评估差异 强化LMT和GLP-1 RA治疗之间的反应预测因素。这项前瞻性观察性研究 将包括116名肥胖青少年，并将重点放在执行功能的三个主要方面- 抑制，认知灵活性和工作记忆-以及使用金标准的奖励反应性 措施对于每个域，单个因素（即，分数）将创建从因素分析和这些潜在的 这些因素将被用作统计模型中的预测因子。据我们所知，这将是第一项研究， 评价青少年对GLP-1 RA治疗的体重减轻反应的神经行为预测因素。此外，委员会认为， 我们将是少数几个前瞻性评估治疗反应的神经行为预测因子的人之一， 减肥维持青少年肥胖。我们的首要目标是超越目前的 “一刀切”的范式，了解如何最好地匹配青少年与肥胖，以个人有效 治疗，这将最大限度地提高临床效果，同时最大限度地减少不必要的风险。

Project Summary/Abstract Neurobehavioral characteristics have the potential to predict initial weight loss and weight loss maintenance in response to various treatment approaches in adolescents with obesity. However, prior research is limited by heavy reliance on cross-sectional analyses and a focus on immersion-type interventions (e.g., inpatient treatment), which are not widely available. Identifying neurobehavioral predictors of response to clinically applicable treatments will stimulate needed progress in the emerging field of precision medicine. Building on a funded, randomized comparative effectiveness trial (R01-DK123273), the current study will prospectively examine neurobehavioral predictors of initial weight loss response and weight loss maintenance for adolescents with obesity participating in intensive lifestyle modification therapy (LMT) or low intensity LMT plus medical management using the glucagon-like peptide-1 receptor agonist (GLP1-RA), semaglutide. In the proposed study we will: 1) identify baseline neurobehavioral predictors of weight loss response in adolescents with obesity undergoing intervention; 2) for participants achieving >5% BMI reduction at 6 months (i.e. initial responders), identify neurobehavioral predictors of weight loss maintenance at 12; and 3) evaluate differences in predictors of response between intensive LMT and GLP-1RA therapy. This prospective, observational study will include 116 adolescents with obesity and will focus on the three main aspects of executive functions - inhibition, cognitive flexibility, and working memory – as well as reward responsivity using gold-standard measures. For each domain, a single factor (i.e., score) will be created from factor analysis and these latent factors will be used as predictors in the statistical models. To our knowledge, this will be the first study to evaluate neurobehavioral predictors of weight loss response to GLP-1RA therapy in adolescents. Moreover, we will be one of few who have prospectively evaluated neurobehavioral predictors of treatment response and weight loss maintenance for adolescents with obesity. Our overarching goal is to move beyond the current “one-size-fits-all” paradigm and understand how to best match adolescents with obesity to personally effective treatment, which will maximize clinical outcomes while minimizing exposure to unnecessary risks.