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.

项目摘要 尽管减肥手术是严重肥胖的最有效治疗方法，但很大一部分患者 经历重大重量，随访更长。因为体重恢复与重新相关 与体重相关的合并症的出现，医疗保健成本增加以及生活质量受损，这是 必须有效地解决这个问题。饮食，运动和行为疗法已证明 逆转重量的效率最小。药物治疗对于解决此临床问题可能很有用。 但是，尚无针对逆转的药物治疗的随机对照试验（RCT） 体重仍然存在。这是一个主要的热间隙，拟议的项目将旨在填补。在这个有力的动力中 精心设计的双盲RCT采用顺序多重分配随机试验 （智能）设计是在减肥手术后总共重新获得体重的120名受试者，最初将在 A 3：3：2与topramate（TPM）50毫克或苯丁胺（PEN）7.5 mg或安慰剂的每日治疗的比率。 4之后 月份，响应者（减肥5％）将继续相同的治疗方法，而无反应者将 将同一药物或苯丁胺/托吡酯7.5/50 mg组合重新融合到更高剂量 （PEN/TPM）在5-12个月中。安慰剂小组将在整个12个月内接受安慰剂。所有主题 在整个研究过程中将获得饮食和生活方式咨询。目标1。确定药物疗法是否 可以逆转肺炎后手术的体重。我们假设与安慰剂相比，这三个活动 药物疗法 - TPM，PEN和PEN/TPM将导致第12个月的体重减轻更高。目标2。 使用倍增标记的进气平衡法客观评估能量摄入的变化 水和DXA。我们假设主动药物疗法将导致能量摄入量的降低 第12个月。目的3。检查肺炎后最常见的不良适应性饮食行为的变化 手术患者 - 磨光，控制丧失的饮食和暴饮暴食。我们假设这是与安慰剂相比 这三种药物疗法将导致适应不良的饮食行为减少。精心选择的电池 探索性结果，包括其他可能的能量平衡变化的调节剂（食欲，夜间进食） 行为，饮食约束，甲状腺激素，瘦素和体育锻炼），额外的效率（alt，ast， 血糖，脂质水平，炎症标记，生活质量和心理健康）和安全性（心率， BP，焦虑，抑郁症状）将被研究。其他效率问题，包括最初的初始问题 将检查治疗，剂量升级与组合策略以及每种自适应干预措施。 这项高度严格研究的结果将为高质量的证据证明 减肥手术后的药物疗法逆转体重恢复。研究结果可能导致变化 减肥手术后，临床实践范例并增强了患者的长期结局。因为 智能设计模仿临床实践，此RCT的发现直接转化为临床实践。