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

1/2，抗肥胖药物芬特明长期有效性临床协调中心：LEAP 试验

• 批准号: 10304557
• 负责人: Jamy D Ard
• 金额: $ 176.62万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304557
• 关键词: Address; Adult; Adverse event; American; Atherosclerosis; Basal metabolic rate; Behavior Therapy; Blood Pressure; Body Weight; Body Weight Changes; Body Weight decreased; Body mass index; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinical; Clinical Trials; Data; Data Coordinating Center; Diabetes Mellitus; Disease; Distant; Drug Prescriptions; Drug usage; Effectiveness; Electrocardiogram; Electronic Health Record; Energy Intake; Enrollment; Event; Future; Glycosylated hemoglobin A; Guidelines; Health; Heart Rate; Hypertension; Insurance; Intervention; Label; Life Style; Lipids; Maintenance; Mediating; Names; Obesity; Observational Study; Outcome; Outcome Measure; Participant; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phentermine; Physical activity; Placebos; Practice Management; Publishing; Randomized Clinical Trials; Randomized Controlled Trials; Research; Risk; Risk Factors; Rogaine; Serious Adverse Event; Sympathomimetics; United States; Ursidae Family; Weight; Weight maintenance regimen; behavior change; behavioral study; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; clinical practice; clinically significant; comorbidity; cost; dietary; efficacy outcomes; energy balance; evidence base; improved; innovation; lifestyle intervention; new therapeutic target; novel; obese patients; obesity treatment; off-label use; patient subsets; primary outcome; programs; randomized trial; stem; 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.

项目摘要/摘要 在美国，超过三分之一的成年人患有肥胖症，许多成年人患有合并症，包括高血压和糖尿病。 全面的生活方式改变是治疗肥胖症的一线方法，但多达一半的患者是 行为改变干预措施无反应，大多数初始响应者继续恢复体重减轻 在2年内。将生活方式干预与抗肥胖药物（AOM）配对可以增强体重减轻和 促进减肥维持。但是，在美国，最近有几个AOM的可用性 药物很少处方。在收到AOM处方的患者中的一小部分中， 通用药物苯甲酸占填充物的76％。芬特明仅被批准用于短期使用，而 当前的肥胖症治疗指南建议长期AOM处方。对长期的担忧 苯丁胺词干的使用是由于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。尽管有这些担忧，尽管迫切需要负担得起 和有效的长期肥胖药物治疗，没有高质量的随机对照试验 苯丁胺单一疗法以检查其有效性，对危险因素的影响或潜在的不良事件的影响 长期。在美国的5个中心，我们将发挥抗肥胖的长期有效性 药物苯丁胺（LEAP）试验 - 安慰剂对照，随机试验，招募1,000名BMI的成年人 27-44.9kg/m2。以一种意图进行治疗的方式，所有参与者都提供基于证据的在线生活方式 干预措施，我们将比较接受24 mg/天苯丁胺与安慰剂的参与者长达24个月。 我们将研究24个月的体重减轻百分比和收缩压的变化的共同结果。 此外，我们将比较群体之间的能量平衡驱动因素的变化，包括静息代谢 速率，热量摄入量，体育锻炼和饮食组成。因为减肥可以改善心脏代谢 健康，我们还将比较心率的变化，血红蛋白A1c，脂质，腰围，动脉粥样硬化 心血管疾病（ASCVD）风险评分和心脏菌株的新型心电图标记。最后，我们将检查 总体不良事件和严重的不良事件率，包括事件心血管疾病或死亡的率。 我们发现的潜在影响很大，无论它们是正面还是负面。如果phonentine 事实证明，对于肥胖患者的长期使用是安全且有效的，它可以立即提供 可用的低成本管理选择。相比之下，如果显示无效，该试验可能会减少标签外 开处方药物，并促进具有经过证实的（尽管昂贵的长期效率）的药物转移。