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.

项目总结