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: 10203955
• 负责人: Benjamin K Canales
• 金额: $ 19.81万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203955
• 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; 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; obese patients; 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.

摘要 越来越多的证据表明，肥胖，糖尿病和肾结石是相互关联的 疾病在整个美国公民中的流行率正在上升。将这三种疾病联系起来 由于食物量、饮食因素和体型都会影响尿成分和矿物质， 排泄其次是尿酸性肾结石（UAN），含或不含草酸钙（CO）成分 肾结石是美国最常见的肾结石类型，仅发生在酸性尿液中（pH < 5.8）。糖尿病合并 超重/肥胖者患UAN/COUAN的风险增加6倍，因为他们无法正确地 在他们的尿液中加入缓冲液（铵）。碱疗法，最常见的是柠檬酸盐的形式，是最常见的。 广泛用于UAN/COUAN的治疗，并已在小系列中报告，随访有限， 完全碱化尿液到正常范围-因此，摆脱病人的疾病。尽管据报道， 使用柠檬酸盐进行简单、实用的UAN/COUAN管理因患者耐受性差、早期 停药，疗效可疑，因为在这一人群中使用的长期证据很少。 此外，患有肾脏疾病的糖尿病患者在所需剂量的柠檬酸钾时可能发生高钾血症， 以及有效的血压药物，如血管紧张素转化酶抑制剂或受体阻滞剂， 会加重高钾血症的风险。最后，这些疗法没有解决两个重要的健康流行病， UAN/COUAN：肥胖和糖尿病。 我们提出了一项为期18个月的可行性试点研究，题为“芬特明/tOpiramate到eND肥胖和尿酸 石头审判”（磅OUT）。我们将30名肥胖和UAN/COUAN患者随机分为两组， FDA批准的减肥药（芬特明加托吡酯-ER; Qsymia® 15 mg/92 mg; Vivus Inc.）或 实用的对照组，其保持其标准药物治疗方案（柠檬酸盐、别嘌呤醇、饮食等）。 Qsymia®不仅有望提供约10%的总体重减轻，而且还具有独特的副作用， 碱化尿液（使其酸性降低）。这一双管齐下的办法预计将减轻 UAN/COUAN和肥胖在这些人，同时建立一个新的类药物治疗肾结石 预防由于30多年来没有新的药物疗法被引入结石病领域，我们 我认为研究目的和研究设计是及时的，可以提供可行的药物替代方案， 柠檬酸盐用于形成尿酸结石的肥胖患者。