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

使用 SMART 设计检查药理学和行为治疗，以治疗代谢和减肥手术后饮食失控并改善体重结果

• 批准号: 10461050
• 负责人: CARLOS M GRILO
• 金额: $ 69.82万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461050
• 关键词: Acute; Adult; Aftercare; Behavior Therapy; Behavioral; Binge Eating; Binge eating disorder; Blinded; Body Weight decreased; Bupropion; Clinical; Data; Double-Blind Method; Eating Behavior; Eating Disorders; Effectiveness; FDA approved; Heterogeneity; Intervention; Literature; Maintenance; Medical; Metabolic; Modeling; Morbid Obesity; Naltrexone; Obesity; Operative Surgical Procedures; Outcome; Outcomes Research; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Pharmacotherapy; Placebos; Randomized; Randomized Controlled Trials; Research; Subgroup; Testing; Treatment Effectiveness; Vyvanse; Weight; bariatric surgery; base; clinical care; comorbidity; design; effective therapy; effectiveness testing; high risk; improved; loss of control over eating; loss of function; novel; obese patients; placebo controlled study; prognostic significance; prospective; psychosocial; response; surgery outcome

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.

尽管代谢和减肥手术（MBS）是严重肥胖的最有效治疗方法，并导致 体重和医疗合并症的强大平均改善，重量结果明显变化 MB和重量恢复后，医疗合并症的重新出现很常见，这表明MBS 一个人通常还不够。迄今为止，只有一个可靠的可修改后MBS减肥预测因子 出现 - “控制丧失饮食”（饮食量），这是暴饮暴食的核心特征。 loc进食，发生在 30％的MBS患者前景与减肥和功能性较差有关。 关于应提供哪些治疗方法以增强MB的结果，几乎没有指导 一般或通过LOC饮食增强高风险亚组的结果。新兴研究表明 肥胖和暴饮暴食（BED）文献适应的饮食的行为治疗 可能有实用性。没有随机对照试验（RCT）检查了任何药理的有效性 MBS后，饮食量或增强体重减轻的代理。这项研究旨在执行两个阶段 RCT测试治疗方法在MBS之后的饮食和改善体重结果的有效性。 在第1阶段RCT中，n = 160例肥胖症患者将随机分配MBS后的Loc-teaging （双盲）在平衡阶乘（2 x 2）设计中，以测试BWL的四个16周条件之一 Naltrexone/Bupropion的药物治疗（NB； FDA批准用于减肥）：BWL+NB，BWL+安慰剂， NB或安慰剂。在第2阶段RCT中，“响应者”对第1阶段治疗（定义为少于一次LOC 饮食）将以相等比例的比例随机（双盲）（第一次分层封闭的随机化 治疗为分层变量）至NB或安慰剂12周。第1阶段治疗的“无反应者”将 随机（双盲）与替代（不同的）药物，lisdexamfetamine（LDX；最近FDA- 批准床）或安慰剂12周。 LOC的独立全面（盲）评估 饮食和肥胖症及其相关结果将在治疗期间每月发生，然后在6-和12-- 完成所有治疗后（即随机化19个月后）后随访。 第一阶段的RCT将提供有关BWL和NB减肥有效性的新发现 药物以及行为和药物治疗的这种特定组合是否有效 MBS之后有饮食和肥胖症的患者。第二阶段的RCT将提供新颖的新颖 在对第1阶段治疗的响应者中，来自受控测试的发现，NB药物是否导致 优越的维护和长期结局比安慰剂。第二阶段的RCT也将在 双盲时尚，在非响应者到1阶段治疗中的时尚 （不同的）LDX药物可增强结果。