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

项目摘要 虽然减肥手术是治疗严重肥胖症最有效的方法，但有很大比例的患者 随着时间的延长，体重会显著增加。因为体重的恢复与重新- 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， 有效管理这一问题势在必行。节食、锻炼和行为疗法已经证明 在逆转体重回升方面的最小效果。药物疗法可能有助于解决这一临床问题。 然而，目前还没有公开发表的逆转卵巢癌药物治疗的随机对照试验(RCT)。 体重又恢复了。这是一个重大的治疗空白，拟议的项目将致力于填补这一空白。在这个功能强大的 采用序贯多任务随机试验的精心设计的双盲随机对照试验 (SMART)设计，总共120名减肥手术后体重恢复的受试者，将在 每日服用托吡酯(TPM)50毫克或苯丙氨酸(Phen)7.5毫克或安慰剂的比例为3：3：2。在4点之后 几个月后，有反应的人(体重减轻5%的≥患者)将继续接受相同的治疗，而无反应的人将继续接受相同的治疗 被重新随机分配到更大剂量的相同药物或芬太尼/托吡酯7.5/50 mg组合 (phen/TPM)在5-12个月。安慰剂组将在整整12个月内接受安慰剂治疗。所有科目 将在整个研究过程中接受饮食和生活方式咨询。目的1.确定药物治疗是否 可以逆转减肥手术后的体重回升。我们假设，与安慰剂相比，这三种药物都很活跃 药物疗法-TPM、phen和phen/TPM将在12个月时导致更大百分比的体重减轻。目标2。 用双标记摄入量平衡法客观评价能量摄入量的变化 水和DXA。我们假设，主动药物治疗将导致能量摄入量在 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--吃草、失控进食和暴饮暴食。我们假设，与安慰剂相比， 所有这三种药物疗法都将减少不适应的饮食行为。精心挑选的一组 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)、额外疗效(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)将进行调查。其他疗效问题，包括最佳首字母 将检查治疗、剂量递增与组合策略，以及每种适应性干预措施。这个 这项高度严格的研究结果将为阿司匹林的有效性和安全性提供高质量的证据 药物疗法逆转减肥手术后体重回升。研究结果可能会导致 临床实践范例和提高减肥手术后患者的长期结果。因为 智能设计模仿临床实践，这项随机对照试验的结果可以直接转化为临床实践。

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.