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

项目摘要/摘要 神经行为特征有可能预测初始体重下降和体重下降维持 肥胖青少年对不同治疗方法的反应。然而，先前的研究受到以下因素的限制 严重依赖横断面分析，注重沉浸式干预(例如，住院患者 治疗)，这些并不是广泛可用的。确定临床疗效的神经行为预测因子 适用的治疗方法将刺激新兴的精准医学领域取得必要的进展。建立在 资助的随机比较有效性试验(R01-DK123273)，本研究将前瞻性地 检查初始减肥反应和减肥维持的神经行为预测因素 肥胖青少年参加强化生活方式调整治疗(LMT)或低强度LMT加治疗 使用胰升糖素样肽-1受体激动剂(GLP1-RA)的药物治疗。在 拟议的研究我们将：1)确定青少年体重减轻反应的基线神经行为预测因素 接受肥胖干预；2)参与者在6个月内(即最初)体重指数下降5% 响应者)，确定12岁时保持体重下降的神经行为预测因素；以及3)评估差异 在预测强化LMT和GLP-1RA治疗效果的指标中。这项前瞻性的观察性研究 将包括116名肥胖青少年，并将重点放在执行职能的三个主要方面- 抑制力、认知灵活性和工作记忆--以及使用黄金标准的奖励反应 措施。对于每个领域，将从因素分析中创建单个因素(即分数)，并且这些潜在的 在统计模型中，将使用因素作为预测因素。据我们所知，这将是第一次研究 评估青少年对GLP-1RA治疗的体重减轻反应的神经行为预测因素。此外， 我们将是少数几个前瞻性评估治疗反应和神经行为预测指标的人之一 为肥胖青少年提供减肥维持服务。我们的首要目标是超越当前的 “放之四海而皆准”的范例，并了解如何最有效地匹配肥胖青少年 治疗，这将使临床结果最大化，同时将暴露于不必要的风险降至最低。

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.