Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial (POuND OUT)

芬特明/托吡酯消除肥胖和尿酸结石试验（英镑）

基本信息

批准号：
9979362
负责人：
Benjamin K Canales
金额：
$ 17.28万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9979362
关键词：
Address Affect Age Alkalies Alkalinization Allopurinol American Ammonium Angiotensin-Converting Enzyme Inhibitors Anorexia Area Bicarbonates Blood Glucose Body Size Body Weight Body Weight decreased Buffers Calcium Calcium Oxalate Carbonic Anhydrase Inhibitors Citrates Control Groups Crystallization Development Diabetes Mellitus Diet Diet Habits Dietary Factors Disease Dose Drug Combinations Epidemic Estrogen receptor positive Ethnic group Excretory function FDA approved Food Future Growth Health Hour Hydrogen Peroxide Image Incidence Individual Inflammation Mediators Intuition Investigational New Drug Application Isoprostanes Kidney Kidney Calculi Kidney Diseases Link Medical Medical Care Costs Minerals Nephrolithiasis Non-Insulin-Dependent Diabetes Mellitus Normal Range Obesity Oral Overweight Oxalates Oxidative Stress Pain Patients Peripheral Pharmaceutical Preparations Pharmacotherapy Phentermine Pilot Projects Plant Roots Population Prevalence Prevention Randomized Randomized Controlled Trials Recurrence Regimen Reporting Research Design Risk Salts Scanning Series Sodium Time Translating Uric Acid Urinary Calculi Urine Validation Weight Weight-Loss Drugs X-Ray Computed Tomography alkalinity blood pressure medication cardiovascular risk factor compliance behavior cost diabetic diet and exercise driving force energy balance follow-up food quality hyperkalemia improved insulin sensitivity novel therapeutics patient tolerability potassium citrate prevent racial and ethnic receptor recruit response sex side effect topiramate urinary

项目摘要

ABSTRACT Mounting evidence indicates that obesity, diabetes mellitus, and kidney stones are inter-connected diseases increasing in prevalence across the entire spectrum of American citizens. Linking these three disease states is intuitive, since food quantity, dietary factors, and body size all affect urinary composition and mineral excretion. Uric acid nephrolithiasis (UAN), with or without components of calcium oxalate (CO), is the second most common kidney stone type in the US and occurs only in acidic urine (pH < 5.8). Diabetics with overweight/obesity have a six-fold increased risk to develop UAN/COUAN because they are unable to properly add buffer (ammonium) to their urine. Alkali therapy, most commonly in the form of citrate salts, is the most widely used treatment for UAN/COUAN and has been reported in small series with limited follow-up to completely alkalinize urine to a normal range – thus, ridding patients of their disease. Despite its reported simplicity, practical UAN/COUAN management with citrate salts is complicated by poor patient tolerance, early cessation, and questionable efficacy as only minimal long-term evidence for its use in this population exists. Furthermore, diabetics with renal disease may develop hyperkalemia on the required doses of potassium citrate, and effective blood pressure medications, such as angiotensin converting enzyme inhibitors or receptor blockers, can worsen the hyperkalemia risk. Finally, these therapies do not address the two important health epidemics that underlie and drive UAN/COUAN: obesity and diabetes. We propose an 18 month, feasibility pilot study entitled, “Phentermine/tOpiramate to eND Obesity and Uric acid stones Trial” (POuND OUT). We will randomize thirty patients with obesity and UAN/COUAN to either an FDA-approved weight loss drug (phentermine plus topiramate-ER; Qsymia® 15mg/92 mg; Vivus Inc.) or a pragmatic control group who remain on their standard medication regimen (citrate salts, allopurinol, diet, etc). Qsymia® is not only expected to provide ~10% total body weight loss but also has a unique side effect of alkalinizing the urine (making it less acidic). This two-pronged approach is expected to reduce the burden of UAN/COUAN and obesity in these individuals while establishing a new class of medications for kidney stone prevention. Since no new drug therapies have been introduced in the area of stone disease in over 30 years, we feel the study objectives and research design are timely and may provide a feasible medication alternative to citrate salts for uric acid stone forming individuals with obesity.

抽象的越来越多的证据表明肥胖、糖尿病和肾结石是相互关联的将这三种疾病联系起来。状态是直观的，因为食物数量、饮食因素和体型都会影响尿液成分和矿物质尿酸性肾结石（UAN），有或没有草酸钙（CO）成分，是第二个。在美国最常见的肾结石类型，仅出现在酸性尿液中（pH < 5.8）。超重/肥胖导致 UAN/COUAN 的风险增加六倍，因为他们无法正确地向尿液中添加缓冲剂（铵）最常见的是柠檬酸盐形式的碱疗法。广泛用于 UAN/COUAN 的治疗，并已进行小系列报道，但后续行动有限将尿液完全碱化至正常范围，从而使患者摆脱疾病，尽管有报道称。使用柠檬酸盐进行简单、实用的 UAN/COUAN 治疗由于患者耐受性差、早期治疗而变得复杂。戒烟和疗效存疑，因为只有极少的长期证据表明其在这一人群中的使用。此外，患有肾病的糖尿病患者在服用所需剂量的柠檬酸钾时可能会出现高钾血症，和有效的降压药物，例如血管紧张素转换抑制剂酶或受体阻滞剂，最后，这些疗法并不能解决两种重要的健康流行病。 UAN/COUAN 的基础和驱动因素：肥胖和糖尿病。我们提议进行一项为期 18 个月的可行性试点研究，题为“芬特明/tOpiramate 消除肥胖和尿酸结石试验”（POUND OUT），我们将 30 名患有 UAN/COUAN 的肥胖患者随机分组。 FDA 批准的减肥药（芬特明加托吡酯-ER；Qsymia® 15mg/92 mg；Vivus Inc.）或务实对照组，保留标准药物治疗方案（柠檬酸盐、别嘌呤醇、饮食等）。 Qsymia® 不仅有望实现约 10% 的总体体重减轻，而且还具有独特的副作用：碱化尿液（降低其酸性）预计可以减轻尿液的负担。 UAN/COUAN 和这些人的肥胖，同时建立一类新的肾结石药物由于 30 多年来没有在结石病领域引入新的药物疗法，因此我们认为研究目标和研究设计是及时的，并且可以提供可行的药物替代方案柠檬酸盐用于肥胖症患者形成尿酸结石。