Pharmacotherapy in conjunction with lifestyle counseling for management of weight regain after bariatric surgery (PROJECT-BARI)

药物治疗与生活方式咨询相结合，用于控制减肥手术后的体重恢复（PROJECT-BARI）

• 批准号: 10678557
• 负责人: KISHORE M GADDE
• 金额: $ 64.77万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-06 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678557
• 关键词: Anxiety; Behavior Therapy; Binge Eating; Body Composition; Body Weight decreased; Clinical Management; Counseling; Desire for food; Diet; Diet therapy; Dietary Intervention; Dose; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Eating Behavior; Energy Intake; Equilibrium; Exercise Therapy; Health Care Costs; Heart Rate; Impairment; Intake; Knowledge; Lead; Leptin; Life Style; Lifestyle Therapy; Lipids; Methods; Morbid Obesity; Outcome; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phentermine; Physical activity; Placebos; Publishing; Quality of life; Questionnaires; Randomized; Randomized Controlled Trials; Safety; Secondary to; Sequential Multiple Assignment Randomized Trial; Testing; Therapeutic; Therapeutic Effect; Thyroid Hormones; Treatment Efficacy; Weight; Weight maintenance regimen; Well in self; adaptive intervention; bariatric surgery; base; clinical practice; comorbidity; depressive symptoms; design; dietary; doubly-labeled water; effective therapy; efficacy evaluation; energy balance; exercise intervention; experience; follow-up; inflammatory marker; loss of control over eating; novel; placebo group; response; restraint; topiramate; total energy expenditure; trial design

Project Summary Although bariatric surgery is the most effective treatment for severe obesity, a large proportion of patients experience significant weight regain with longer follow-up. Because weight regain is associated with re- emergence of weight-related comorbidities, increased health care costs, and impaired quality of life, it is imperative to effectively manage this problem. Diet, exercise, and behavior therapy have demonstrated minimal efficacy in reversing weight regain. Pharmacotherapy could be useful to manage this clinical problem. However, there are no published randomized controlled trials (RCTs) of pharmacotherapy for reversal of weight regain. This is a major therapeutic gap, which the proposed project will aim to fill. In this well-powered meticulously designed double-blind RCT employing a Sequential Multiple Assignment Randomized Trial (SMART) design, a total of 120 subjects with weight regain after bariatric surgery, will be initially randomized in a 3:3:2 ratio to daily treatment with topiramate (TPM) 50 mg or phentermine (PHEN) 7.5 mg or placebo. After 4 months, responders (those with ≥5% weight loss) will continue the same treatment, while nonresponders will be re-randomized to a higher dose of the same drug or phentermine/topiramate 7.5/50 mg combination (PHEN/TPM) during Months 5-12. The placebo group will receive placebo for the full 12 months. All subjects will receive diet and lifestyle counseling throughout the study. Aim 1. To determine whether pharmacotherapy can reverse post-bariatric surgery weight regain. We hypothesize that, compared to placebo, all three active drug therapies – TPM, PHEN, and PHEN/TPM will lead to greater percent weight loss at Month 12. Aim 2. To examine change in energy intake objectively assessed with the Intake-Balance Method using doubly labeled water and DXA. We hypothesize that active drug therapy will lead to greater reduction in energy intake at Month 12. Aim 3. To examine changes in the most common maladaptive eating behaviors in the post-bariatric surgery patients - grazing, loss-of-control eating, and binge eating. We hypothesize that, compared to placebo, all three drug therapies will lead to decreased maladaptive eating behaviors. A battery of carefully chosen exploratory outcomes including other likely modulators of changes in energy balance (appetite, night eating behavior, dietary restraint, thyroid hormones, leptin, and physical activity), additional efficacy (ALT, AST, glycemia, lipid levels, inflammatory markers, quality of life, and psychological wellbeing), and safety (heart rate, BP, anxiety, depressive symptoms) will be investigated. Additional efficacy questions including the best initial treatment, dose escalation vs combination strategy, and each adaptive intervention will be examined. The findings of this highly rigorous study will provide high-quality evidence for the efficacy and safety of pharmacotherapy in reversing weight regain after bariatric surgery. Study results could lead to a change in clinical practice paradigms and enhance long-term outcomes for patients after bariatric surgery. Because the SMART design mimics clinical practice, the findings of this RCT are directly translatable to clinical practice.

项目概要 虽然减肥手术是治疗严重肥胖最有效的方法，但很大一部分患者 随着随访时间的延长，体重会显着回升，因为体重回升与体重恢复有关。 与体重相关的合并症的出现、医疗费用的增加以及生活质量的下降， 事实证明，饮食、运动和行为疗法势在必行。 药物治疗在逆转体重反弹方面效果甚微，可能有助于解决这一临床问题。 然而，尚无已发表的逆转药物治疗的随机对照试验（RCT）。 这是一个主要的治疗空白，拟议的项目旨在填补这一空白。 采用序贯多重分配随机试验精心设计的双盲 RCT (SMART) 设计，共有 120 名减肥手术后体重恢复的受试者，最初将被随机分组 按 3:3:2 的比例每日服用托吡酯 (TPM) 50 mg 或芬特明 (PHEN) 7.5 mg 或安慰剂 4 次后。 几个月后，有反应者（体重减轻 ≥5% 的人）将继续相同的治疗，而无反应者将 重新随机分配至更高剂量的相同药物或芬特明/托吡酯 7.5/50 mg 组合 (PHEN/TPM) 在第 5-12 个月期间，安慰剂组将在整个 12 个月内接受安慰剂。 在整个研究过程中接受饮食和生活方式咨询 目的 1. 确定是否进行药物治疗。 我们再次认识到，与安慰剂相比，这三种药物都可以逆转减肥手术后的体重反弹。 药物治疗 – TPM、PHEN 和 PHEN/TPM 将在第 12 个月时实现更大百分比的体重减轻。目标 2. 检查能量摄入的变化，使用双标记的摄入平衡法客观评估 我们追求积极的药物治疗将导致能量摄入的更大减少。 第 12 个月。目标 3：检查减肥后最常见的适应不良饮食行为的变化 手术患者 - 放牧、饮食失控和暴饮暴食。 所有三种药物疗法都会导致一系列精心选择的不良饮食行为的减少。 探索性结果，包括能量平衡变化的其他可能调节因素（食欲、夜间进食 行为、饮食限制、甲状腺激素、瘦素和体力活动）、额外功效（ALT、AST、 血糖、血脂水平、炎症标志物、生活质量和心理健康）和安全性（心率、 血压、焦虑、抑郁症状）将被调查，包括最佳初始疗效问题。 将检查治疗、剂量递增与联合策略以及每种适应性干预措施。 这项高度严谨的研究结果将为以下药物的有效性和安全性提供高质量的证据： 药物治疗逆转减肥手术后体重反弹的研究结果可能会导致体重变化。 临床实践范例并提高减肥手术后患者的长期结果。 SMART 设计模仿临床实践，该随机对照试验的结果可直接转化为临床实践。