2/2, Data Coordinating Center for the Long-term Effectiveness of the Anti-obesity medication Phentermine: the LEAP Trial

2/2，抗肥胖药物芬特明长期有效性数据协调中心：LEAP 试验

• 批准号: 10490310
• 负责人: Nicholas M. Pajewski
• 金额: $ 30.95万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490310
• 关键词: Adult; Adverse event; American; Atherosclerosis; Basal metabolic rate; Behavior Therapy; Biometry; Blood Pressure; Body Weight; Body Weight Changes; Body Weight decreased; Body mass index; Cardiac; Cardiovascular Diseases; Cessation of life; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Communication; Data; Data Coordinating Center; Databases; Development; Diabetes Mellitus; Disease; Double-Blind Method; Drug Prescriptions; Effectiveness; Electrocardiogram; Energy Intake; Enrollment; Ensure; Glycosylated hemoglobin A; Guidelines; Health; Heart Rate; Hypertension; Incidence; Informatics; Infrastructure; Insurance; Intervention; Label; Life Style; Lipids; Maintenance; Manuals; Mediating; Methodology; Multicenter Trials; Names; Obesity; Online Systems; Outcome; Participant; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phentermine; Physical activity; Placebo Control; Placebos; Procedures; Process; Protocols documentation; Randomized Clinical Trials; Randomized Controlled Trials; Research; Research Design; Risk; Risk Factors; Rogaine; Security; Serious Adverse Event; Statistical Data Interpretation; Sympathomimetics; Testing; TimeLine; United States; Ursidae Family; Weight; Weight maintenance regimen; acronyms; behavior change; behavioral study; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; cardiovascular risk factor; clinical research site; comorbidity; cost; data management; dietary; energy balance; evidence base; experience; follow-up; forest; improved; lifestyle intervention; medical schools; mortality; novel; obese patients; obesity treatment; off-label use; participant safety; patient subsets; primary outcome; programs; randomized trial; recruit; sound; stem; success; tool; treatment guidelines; uptake; waist circumference

PROJECT SUMMARY/ABSTRACT Over one-third of adults in the US have obesity, many with comorbidities including hypertension and diabetes. Comprehensive lifestyle change is the first-line approach to treating obesity, but as many as half of patients are non-responsive to behavior change interventions, and the majority of initial responders go on to regain lost weight within 2 years. Pairing lifestyle intervention with an antiobesity medication (AOM) can enhance weight loss and promote weight loss maintenance. However, despite the recent availability of several AOMs in the US, these medications are rarely prescribed. Among the small subset of patients who do receive an AOM prescription, the generic medication Phentermine accounts for 76% of fills. Phentermine is only approved for short-term use, while current guidelines for treatment of obesity recommend long-term AOM prescribing. Concerns about longer-term use of phentermine stem from the fact that it can increase heart rate and blood pressure, theoretically increasing risk of incident cardiovascular disease. Despite these concerns, and despite the pressing need for affordable and effective long-term obesity pharmacotherapy, there have been no high-quality, randomized controlled trials of phentermine monotherapy to examine its efficacy, impact on risk factors, or potential adverse events if used long-term. At 5 centers across the United States, we will conduct the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial—a placebo-controlled, randomized trial, enrolling 1,000 adults with BMI 27-44.9kg/m2. In an intent-to-treat fashion, with all participants provided with an evidence-based online lifestyle intervention, we will compare participants receiving 24 mg/day of phentermine vs. placebo for up to 24 months. We will examine co-primary outcomes of percent weight loss and change in systolic blood pressure at 24 months. Additionally, we will compare between groups changes in drivers of energy balance, including resting metabolic rate, caloric intake, physical activity and dietary composition. Because weight loss can improve cardiometabolic health, we will also compare changes in heart rate, hemoglobin A1c, lipids, waist circumference, atherosclerotic cardiovascular disease (ASCVD) risk score, and novel ECG markers of cardiac strain. Finally, we will examine overall adverse event and serious adverse event rate, including rates of incident cardiovascular disease or death. The potential impact of our findings is large regardless of whether they are positive or negative. If phentermine were shown to be safe and effective for long-term use in patients with obesity, it could provide an immediately available low-cost option for weight management. In contrast, if shown ineffective, the trial could reduce off-label prescribing of the medication and promote a shift to drugs with proven, albeit costly, long-term effectiveness.

项目总结/摘要 在美国，超过三分之一的成年人患有肥胖症，许多人患有高血压和糖尿病等合并症。 全面改变生活方式是治疗肥胖的一线方法，但多达一半的患者 对行为改变干预无反应，大多数最初的反应者继续恢复体重 两年内。将生活方式干预与抗肥胖药物（AOM）配对可以促进减肥， 促进减肥维持。然而，尽管最近在美国有几种AOM， 很少开处方药。在接受AOM处方的一小部分患者中， 非专利药物芬特明占填充量的76%。芬特明只被批准用于短期使用，而 目前治疗肥胖症的指南推荐长期AOM处方。长期关注 使用芬特明干的事实，它可以增加心率和血压，理论上增加 发生心血管疾病的风险。尽管存在这些担忧，尽管迫切需要负担得起的 和有效的长期肥胖药物治疗，目前还没有高质量的随机对照试验 芬特明单药治疗，以检查其疗效，对风险因素的影响，或潜在的不良事件，如果使用 长期的。在美国的5个中心，我们将进行抗肥胖的长期有效性研究。 芬特明（LEAP）试验-一项安慰剂对照的随机试验，招募了1,000名BMI 27-44.9kg/m2.以意向治疗的方式，为所有参与者提供基于证据的在线生活方式 在干预期间，我们将比较接受24 mg/天芬特明与安慰剂的参与者长达24个月。 我们将检查24个月时体重减轻百分比和收缩压变化的共同主要结局。 此外，我们将比较各组之间能量平衡驱动因素的变化，包括静息代谢 速率、热量摄入、体力活动和饮食组成。因为减肥可以改善心脏代谢， 健康，我们还将比较心率，血红蛋白A1 c，血脂，腰围，动脉粥样硬化 心血管疾病（ASCVD）风险评分和心脏劳损的新型ECG标志物。最后，我们将研究 总体不良事件和严重不良事件发生率，包括心血管疾病或死亡的发生率。 我们的研究结果的潜在影响是巨大的，无论它们是积极的还是消极的。如果芬特明 被证明是安全和有效的长期使用的肥胖患者，它可以提供一个立即 可提供低成本的体重管理选项。相反，如果证明无效，试验可以减少标签外使用， 处方的药物，并促进药物的转变，证明，虽然昂贵，长期有效。