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）

• 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
• 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

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连接的 在整个美国公民中，疾病的患病率增加。连接这三种疾病 状态是直观的，因为食物数量，饮食因素和体型都会影响尿成分和矿物质 尿酸肾物石（UAN），有或没有草酸钙（CO）的成分，是第二个 美国最常见的肾结石类型，仅在酸性尿液中发生（pH <5.8）。糖尿病患者 超重/肥胖的风险增加了六倍，因为它们无法正确地发展UAN/COUAN 将缓冲液（铵）添加到尿液中。碱性疗法最常见于柠檬酸盐的形式，是最常见的 广泛使用UAN/COUAN的治疗 将尿液完全碱化到正常范围，因此使患者患有疾病。尽管报道了它 简单性，实用的UAN/COUAN用柠檬酸盐管理因较差的患者耐受性而变得复杂，早期 停止和可疑效率仅是其在该人群中使用的最小长期证据。 此外，患有肾脏疾病的糖尿病患者可能会在所需剂量的柠檬酸钾剂量上产生高钾血症， 和有效的血压药物，例如血管紧张素转化酶抑制剂或接收器阻滞剂， 可能会担心高钾血症的风险。最后，这些疗法无法解决两个重要的健康情节 基础和驾驶uan/couan：肥胖和糖尿病。 我们提出了一项18个月的可行性试验研究，题为“苯丁胺/托吡酯终止肥胖和尿酸 石头试验”（磅）。我们将将肥胖症和uan/couan的患者随机随机 FDA批准的减肥药（Phentermine Plus tupiramate-er;QSymia®15mg/92mg; Vivus Inc.）或A 务实的对照组，他的标准药物治疗方案（柠檬酸盐，别嘌醇，饮食等）。 QSymia®不仅预期提供约10％的总体重减轻，而且具有独特的副作用 碱化尿液（减少酸性）。预计这种两管齐的方法将减少 在这些人中为肾结石建立新的药物时，uan/couan and肥胖 预防。由于在30多年内没有在石材疾病领域引入任何新药物疗法，我们 认为研究目标和研究设计是及时的，可以提供可行的药物替代品 尿酸石的柠檬酸盐，形成肥胖的个体。