1/2, Clinical Coordinating Center for the Long-term Effectiveness of the Anti-obesity medication Phentermine: the LEAP Trial

项目摘要/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并存疾病。 全面改变生活方式是治疗肥胖的一线方法，但多达一半的患者是这样做的 对行为改变干预没有反应，大多数最初的反应者继续减肥 在两年内。生活方式干预与抗肥胖药物(AOM)相结合可以促进减肥和 推动减肥养生。然而，尽管最近在美国有几个AOM可用，但这些 很少有人开药。在接受AOM处方的一小部分患者中， 仿制药PhenTere占填充物的76%。芬太尼仅被批准短期使用，而 目前的肥胖治疗指南建议长期服用AOM处方。对更长期的担忧 芬太尼的使用源于这样一个事实，即它可以提高心率和血压，理论上可以 发生心血管疾病的风险。尽管有这些关切，尽管迫切需要负担得起的 而长期有效的肥胖症药物治疗，还没有高质量的随机对照试验 检查其疗效、对危险因素的影响或潜在不良事件(如果使用) 长期的。在美国的5个中心，我们将进行减肥的长期有效性 药物PhenTere(LEAP)试验--一项安慰剂对照的随机试验，招募了1000名患有BMI的成年人 27-44.9公斤/平方米。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 在干预方面，我们将比较每天服用24毫克苯丙氨酸的参与者和服用安慰剂的患者长达24个月的情况。 我们将检查体重减轻百分比和24个月后收缩压变化的共同主要结果。 此外，我们还将比较不同组之间能量平衡驱动因素的变化，包括静息代谢 速度、卡路里摄入量、体力活动和饮食结构。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A1c、血脂、腰围、动脉粥样硬化的变化 心血管疾病(ASCVD)风险评分，以及心脏劳损的新心电标记物。最后，我们将检查 总体不良事件和严重不良事件发生率，包括心血管疾病发生率或死亡率。 我们的发现的潜在影响是巨大的，无论它们是积极的还是消极的。如果是苯末端子 对于肥胖症患者的长期使用是安全有效的，它可以立即提供 提供低成本的体重管理选项。相反，如果被证明无效，该试验可能会减少非处方 开出药物处方，并促进向长期有效、但成本高昂的药物的转变。

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.