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: 10267187
• 负责人: CARLOS M GRILO
• 金额: $ 70.82万
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267187
• 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）是治疗严重肥胖症最有效的方法，并且会导致 体重和合并症的平均改善显着，体重结果差异显着 MBS 后体重恢复且合并症复发的情况很常见，这表明 MBS 迄今为止，仅靠一种可靠的、可修改的 MBS 后体重减轻预测指标往往是不够的。 出现了“失控饮食”（LOC-eating），这是暴食的核心特征，发生在。 30% 的 MBS 患者可能会出现较差的减肥和功能结果。 关于应提供哪些治疗来增强 MBS 结局的指导很少 新兴研究表明，一般或提高高风险亚组的结果。 LOC 饮食的行为疗法改编自肥胖和暴食症 (BED) 文献 没有随机对照试验（RCT）检验过任何药理学的有效性。 用于 LOC 饮食或增强 MBS 后减肥的药物 本研究旨在进行两个阶段。 随机对照试验 (RCT) 旨在测试 LOC 饮食治疗和改善 MBS 后体重结果的有效性。 在第 1 阶段随机对照试验中，N=160 名 MBS 后肥胖且食用 LOC 的患者将被随机分配 （双盲）采用平衡因子 (2 X 2) 设计，以四个 16 周条件之一来测试 BWL 和 纳曲酮/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，对第 1 阶段治疗的“反应者”（定义为每周少于一次 LOC）。 饮食）将以等比例随机（双盲）（分层分组随机化，首先 治疗作为分层变量），对 NB 或安慰剂进行 12 周的“无反应”治疗。 被随机（双盲）到另一种（不同的）药物，赖右苯丙胺（LDX；最近 FDA- 批准用于 BED）或安慰剂 12 周的 LOC 独立综合（盲）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 岁和 12 岁发生 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有关 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有效 MBS 后出现 LOC 饮食和肥胖的患者第二阶段随机对照试验将提供新的和新颖的。 一项对照测试的结果，在第一阶段治疗的反应者中，NB 药物是否会导致 第二阶段随机对照试验还将探索比安慰剂更好的维持和长期结果。 双盲时尚，在第一阶段治疗无反应者中，是否转向替代方案 （独特）LDX 药物可以改善结果。