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.

虽然代谢和减肥手术（MBS）是治疗严重肥胖症最有效的方法， 体重和医学合并症的稳健平均改善，体重结果存在显著差异 MBS和体重恢复后，常见的是医学合并症的复发，这表明MBS 光靠自己往往不够。到目前为止，只有一个可靠的可修改的预测后MBS体重减轻， 出现了“失控进食”（LOC进食），这是暴饮暴食的核心特征。食腐病，发生在 30%的患者在MBS后，与较差的体重减轻和功能结局相关。 对于应该提供什么样的治疗来增强MBS的结果，几乎没有指导。 一般或提高高风险亚组与暴食的结果。新兴研究表明 针对LOC进食的行为疗法是从肥胖和暴食症（BED）文献中改编而来的， 可能有实用价值。没有随机对照试验（RCT）检查任何药理学的有效性。 用于吃LOC或增强MBS后的体重减轻的药剂。本研究的目的是进行两个阶段 随机对照试验，以测试治疗LOC进食和改善MBS后体重结果的有效性。 在第1阶段RCT中，将随机分配N=160例MBS后肥胖和吃LOC的患者 （双盲）在平衡析因（2 X 2）设计中，在四个16周条件之一中测试BWL， 纳洛酮/安非他酮药物治疗（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，第1阶段治疗的“应答者”（定义为每周少于一次的治疗） 进食）将以相等比例随机化（双盲）（分层区组随机化， 治疗作为分层变量）至NB或安慰剂治疗12周。第1阶段治疗的“无应答者”将 随机（双盲）接受替代（不同）药物利右苯丙胺（LDX;最近FDA- 批准用于BED）或安慰剂12周。独立的全面（盲法）评估 饮食和肥胖及其相关的结果将在治疗期间每月发生，然后在6- 12- 完成所有治疗后的1个月随访（即，随机化后19个月）。 第一阶段随机对照试验将提供关于BWL和NB减肥有效性的新发现 药物治疗以及这种行为和药物治疗的特定组合是否对 MBS后有LOC饮食和肥胖的患者。第二阶段RCT将提供新的和新颖的 在第1阶段治疗的应答者中，来自对照试验的结果，NB药物是否导致 与安慰剂相比，维持治疗和长期结局具有上级优势。第二阶段RCT还将探索， 双盲方式，在第1阶段治疗的无应答者中，是否转换为替代治疗 （不同）LDX药物可改善结果。