Behavioral and Pharmacological Treatments to Enhance Weight Outcomes after Metabolic and Bariatric Surgery

项目摘要。 预计肥胖和严重肥胖的比率将继续上升到令人震惊的水平。到2030年，超过51%的 美国的成年人预计将患有肥胖症，严重肥胖症的人数增加了130%。这些惊人的增长率 考虑到严重的疾病和经济负担， 肥胖随着严重肥胖率的持续快速上升，代谢和减肥手术（MBS）的使用正在逐渐减少。 预计将增加。MBS是治疗严重肥胖症最有效的方法， 和长期体重减轻，以及改善医疗和心理社会共病。然而，体重 MBS后的结果明显不同，这表明单靠手术是不够的， 重度肥胖亚组。MBS后体重反弹是常见的，也是一个主要问题，特别是因为 体重恢复与复发或甚至恶化的医学合并症有关。尽管需要 由于肥胖的慢性性和复发的风险，MBS后正在进行的肥胖治疗几乎没有指导 根据经验数据确定应提供何种治疗。事实上，没有前瞻性研究或 随机对照试验（RCT）已经检查了药物的有效性， (and有限的）随机对照试验已经检查了行为体重减轻（BWL），以增强MBS后的体重减轻。 因此，结合药物和手动BWL治疗以提高体重结局的严格RCT 在MBS之后，降低个人和公共肥胖健康成本的下一步势在必行。来填补这个 在MBS领域的关键差距，拟议的随机对照试验将测试一个严格的手动BWL的有效性， FDA批准的减肥药（纳洛酮+安非他酮/NB），单独使用和联合使用，用于改善 体重减轻、心血管风险因素和心理社会功能。N=160例肥胖患者（BMI≥30或 ≥27岁，伴有医学合并症），接受MBS且体重结局不理想的患者将随机 在平衡析因（2 × 2）设计中分配（双盲）至4种24周条件之一：BWL+NB， BWL+安慰剂、仅NB（无BWL）或仅安慰剂（无BWL）。结果变量的确定基于 NB、NIH ADOPT指南和概念相关的肥胖症的主要严格减肥RCT NB和BWL的变量。独立的结局评估将决定停药后的结局 治疗18个月。拟议的随机对照试验将提供关于 药物治疗和BWL对快速增长的肥胖亚组的效用和有效性，并将告知 管理慢性肥胖的护理模式，以提高MBS后的结果。这将是第一个随机对照试验 MBS后肥胖症的任何药物治疗; 2）检查BWL和NB，单独和组合， 接受MBS的患者的体重减轻和相关特征;以及3）检查 联合治疗模式的治疗效果，包括治疗后的长期随访评估 治疗实施

Project Summary. Rates of obesity and severe obesity are expected to continue to rise to alarming levels. By 2030, over 51% of adults in the US are expected to have obesity with a 130% increase in severe obesity. These staggering rates and projected future increases are deeply concerning given the substantial disease and economic burden of obesity. As severe obesity rates continue to rapidly rise, the use of metabolic and bariatric surgeries (MBS) is expected to increase. MBS is the most effective treatment for severe obesity and results in impressive acute and long-term weight loss, as well as improvement of medical and psychosocial comorbidities. Yet, weight outcomes are markedly variable after MBS, suggesting that surgery alone is not enough for a sizeable subgroup with severe obesity. Weight regain after MBS is common and a major concern, particularly because weight regain is associated with recurring or even worsening medical comorbidities. Despite the need for ongoing obesity treatment after MBS due to the chronicity of obesity and risk for regain, there is little guidance as to what treatment(s) should be provided based on empirical data. In fact, no prospective studies or randomized controlled trials (RCTs) have examined the effectiveness of pharmacologic agents and very few (and limited) RCTs have examined behavioral weight loss (BWL) to enhance weight losses following MBS. Thus, rigorous RCTs combining pharmacological and manualized BWL treatment to enhance weight outcomes after MBS is an imperative next step to reduce personal and public health costs of obesity. To help fill this critical gap in the MBS field, the proposed RCT will test the effectiveness of a rigorous manualized BWL and a FDA-approved weight-loss agent (naltrexone+bupropion/NB), alone and in combination, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning. N=160 patients with obesity (BMI≥30 or ≥27 with a medical comorbidity) who underwent MBS and have suboptimal weight outcomes will be randomly assigned (double-blind) in balanced factorial (2 X 2) design, to one of four 24-week conditions: BWL+NB, BWL+Placebo, NB-only (No BWL), or Placebo-only (No BWL). Outcome variables were determined based on the leading rigorous weight loss RCTs for obesity with NB, NIH ADOPT guidelines, and conceptually-relevant variables for NB and BWL. Independent outcome assessments will determine outcomes after discontinuation of treatments through 18 months. The proposed RCT will provide important new clinical findings regarding the utility and effectiveness of pharmacotherapy and BWL for a rapidly growing obesity subgroup and will inform care models for managing chronic obesity to enhance outcomes after MBS. This will be the first RCT to 1) test any pharmacologic treatment for obesity after MBS; 2) examine BWL and NB, alone and in combination, for weight loss and associated features in patients who have undergone MBS; and 3) examine the durability of treatment effects from combined treatment modalities by including long-term follow-up assessments after treatment delivery.