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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要美国超过三分之一的成年人患有肥胖症，其中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措施没有反应，大多数最初反应者随后体重又恢复了将生活方式干预与抗肥胖药物 (AOM) 结合起来可以在 2 年内增强减肥效果。然而，尽管美国最近出现了几种 AOM，但这些药物仍然有效。在接受 AOM 处方的一小部分患者中，很少开出药物。仿制药芬特明占填充药的 76%，而芬特明仅被批准用于短期使用。目前的肥胖治疗指南建议长期服用 AOM 处方，但对长期的担忧。芬特明的使用源于它可以增加心率和血压，理论上可以增加尽管有这些担忧，尽管迫切需要负担得起的药物。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、对危险因素的影响或使用时潜在的不良事件我们将在美国的 5 个中心进行长期有效性的抗肥胖研究。芬特明 (LEAP) 试验——一项安慰剂对照、随机试验，招募了 1,000 名 BMI 成年人 27-44.9kg/m2 以意向治疗方式，为所有参与者提供基于证据的在线生活方式。在干预中，我们将比较接受 24 毫克/天芬特明与安慰剂的参与者长达 24 个月的时间。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果。此外，我们将比较各组之间能量平衡驱动因素的变化，包括静息代谢因为减肥可以改善心脏代谢。健康方面，我们还会比较心率、血红蛋白A1c、血脂、腰围、动脉粥样硬化的变化心血管疾病（ASCVD）风险评分和心脏劳损的新心电图标记最后，我们将检查。总体不良事件和严重不良事件发生率，包括心血管疾病或死亡率的发生率。无论是积极的还是消极的，我们的研究结果的潜在影响都是巨大的。已被证明对肥胖患者长期使用是安全有效的，它可以立即提供相比之下，如果证明无效，该试验可以减少标签外体重管理。开出药物处方，并促进转向使用经证实但成本高昂的长期有效性药物。