Using a SMART Design to Examine Pharmacological and Behavioral Treatments to Treat Loss-of-Control Eating and Improve Weight Outcomes after Metabolic and Bariatric Surgery

虽然代谢和减肥手术(MBS)是治疗严重肥胖症最有效的治疗方法，但它会导致 体重和医学合并症的强劲平均改善，体重结果明显不同 MBS后体重回升与内科合并症复发是常见的，提示MBS 单枪匹马往往是不够的。到目前为止，只有一个可靠的、可修改的后MBS后体重下降预测指标 出现了“失控进食”，这是暴饮暴食的核心特征。LoC进食，这发生在 30%的患者服用MBS后，预期体重减轻和功能结果较差。 对于应该提供哪些治疗来提高MBS的预后，目前几乎没有指导意见 一般或改善进食低碳水化合物的高危亚组的预后。新出现的研究表明 LOC进食的行为疗法源于肥胖和暴饮暴食障碍(Bed)的文献 可能会有用处。没有随机对照试验(RCT)检验过任何药物的有效性。 吃低碳水化合物或在服用MBS后加强减肥的药物。本研究旨在进行两个阶段的研究 RCT以测试治疗进食LOC和改善MBS后体重结果的有效性。 在第一阶段随机对照试验中，N=160名MBS后肥胖和进食LOC的患者将被随机分配 (双盲)在平衡析因(2×2)设计中，到四个16周条件之一来测试BWL和 纳曲酮/安非他酮(NB；FDA批准用于减肥)：BWL+NB，BWL+安慰剂， NB，或安慰剂。在第二阶段随机对照试验中，对第一阶段治疗(定义为每周少于一次的LOC)的“应答者” 饮食)将按相同比例随机(双盲)(分层区组随机 治疗作为分层变量)，以NB或安慰剂为准，为期12周。对第一阶段治疗没有反应的人将会 随机(双盲)服用另一种(不同的)药物，来司非他明(LDX；最近FDA- 批准上床)或服用安慰剂12周。对LOC的独立、全面(盲目)评估 饮食和肥胖及其相关结果将在治疗期间每月发生一次，然后在6-和12- 在完成所有治疗后(即随机分组后19个月)进行一个月的随访。 第一阶段随机对照试验将提供关于BWL和NB减肥效果的新发现 药物治疗以及这种行为和药物治疗的具体组合是否对 MBS后有LOC进食和肥胖的患者。第二阶段RCT将提供新的和新颖的 在阶段1治疗的应答者中进行对照测试的结果，NB药物治疗是否会导致 比安慰剂更好的维护和更长期的结果。第二阶段RCT也将探索，在 双盲方式，在对阶段1治疗无效的人中，无论是否切换到替代方案 (独特)LDX药物可提高疗效。

Although metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity and results in robust average improvements in weight and medical comorbidities, weight outcomes are markedly variable after MBS and weight regain with reoccurrence of medical comorbidities is common, suggesting that MBS alone is often not enough. To date, only one reliable modifiable predictor of post-MBS weight loss has emerged - “loss-of-control eating” (LOC-eating), the core feature of binge eating. LOC eating, which occurs in 30% of patients following MBS, is associated prospectively with poorer weight-loss and functioning outcomes. There exists little guidance as to what treatments should be provided to enhance MBS outcomes in general or to enhance outcomes among the high-risk subgroup with LOC eating. Emerging research suggests that behavioral treatments for LOC-eating adapted from obesity and binge-eating disorder (BED) literatures might have utility. No randomized controlled trials (RCTs) have examined effectiveness of any pharmacologic agents for either LOC-eating or to enhance weight loss following MBS. This study aims to perform a two-stage RCT to test the effectiveness of treatments for LOC-eating and improving weight outcomes following MBS. In Stage 1 RCT, N=160 patients with obesity and LOC-eating following MBS will be randomly assigned (double-blind) in a balanced factorial (2 X 2) design, to one of four 16-week conditions to test BWL and pharmacotherapy with naltrexone/bupropion (NB; FDA-approved for weight-loss): BWL+NB, BWL+Placebo, NB, or Placebo. In Stage 2 RCT, “Responders” to Stage 1 treatments (defined as less than once weekly LOC eating) will be randomized (double-blind) in equal proportions (stratified blocked randomization with first treatment as stratifying variable) to NB or placebo for 12 weeks. “Non-responders” to Stage 1 treatments will be randomized (double-blind) to an alternative (distinct) medication, lisdexamfetamine (LDX; recently FDA- approved for BED) or to placebo for 12 weeks. Independent comprehensive (blinded) assessments of LOC eating and obesity and their associated outcomes will occur monthly during treatments and then at 6- and 12- month follow-ups after completing all treatments (i.e., 19 months after randomization). The first stage RCT will provide new findings regarding effectiveness of BWL and of NB weight-loss medication and whether this specific combination of behavioral and pharmacologic treatments is effective for patients who have LOC-eating and obesity following MBS. The second stage RCT will provide new and novel findings from a controlled test, amongst Responders to Stage 1 treatments, whether NB medication results in superior maintenance and longer-term outcomes than placebo. The second stage RCT will also explore, in double-blind fashion, amongst Non-responders to Stage 1 treatments, whether switching to an alternative (distinct) LDX medication enhances outcomes.