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:10203955
- 负责人:
- 金额:$ 19.81万
- 依托单位:
- 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 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgeAlkaliesAlkalinizationAllopurinolAmericanAmmoniumAngiotensin-Converting Enzyme InhibitorsAnorexiaAreaBicarbonatesBlood GlucoseBody SizeBody WeightBody Weight decreasedBuffersCalciumCalcium OxalateCarbonic Anhydrase InhibitorsCitratesControl GroupsCrystallizationDevelopmentDiabetes MellitusDietDiet HabitsDietary FactorsDiseaseDoseDrug CombinationsEpidemicEthnic groupExcretory functionFDA approvedFoodFutureGrowthHealthHourHydrogen PeroxideImageIncidenceIndividualInflammation MediatorsIntuitionInvestigational New Drug ApplicationIsoprostanesKidneyKidney CalculiKidney DiseasesLinkMedicalMedical Care CostsMineralsNephrolithiasisNon-Insulin-Dependent Diabetes MellitusNormal RangeObesityOralOverweightOxalatesOxidative StressPainPatientsPeripheralPharmaceutical PreparationsPharmacotherapyPhenterminePilot ProjectsPlant RootsPopulationPrevalencePreventionRandomizedRandomized Controlled TrialsRecurrenceRegimenReportingResearch DesignRiskSaltsScanningSeriesSodiumTimeTranslatingUric AcidUrinary CalculiUrineValidationWeightWeight-Loss DrugsX-Ray Computed Tomographyalkalinityblood pressure medicationcardiovascular risk factorcompliance behaviorcostdiabeticdiet and exercisedriving forceenergy balancefollow-upfood qualityhyperkalemiaimprovedinsulin sensitivitynovel therapeuticsobese patientspatient tolerabilitypotassium citratepreventracial and ethnicreceptorrecruitresponsesexside effecttopiramateurinary
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.
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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Benjamin K Canales其他文献
DIFFERNTIAL RENAL TISSUE PROTEIN PROFILING IN A MOUSE MODEL OF HYPERCALCIURIA: EFFECT OF HIGH OXALATE DIET
- DOI:
10.1016/s0022-5347(09)62022-x - 发表时间:
2009-04-01 - 期刊:
- 影响因子:
- 作者:
Benjamin K Canales;Leticia Reyes;Patricia A Glenton;Marjorie Chow;Sixue Chen;Saeed R Khan - 通讯作者:
Saeed R Khan
SYMPTOMS AND RISK FACTORS ASSOCIATED WITH FIRST UTI IN COLLEGE-AGED WOMEN: A PROSPECTIVE COHORT STUDY
- DOI:
10.1016/s0022-5347(09)60410-9 - 发表时间:
2009-04-01 - 期刊:
- 影响因子:
- 作者:
Charles R Vincent;Mary Brown;Leticia Reyes;Benjamin K Canales;Keith Muller;Veronique Vincent;Qin Li;Tami Thomas - 通讯作者:
Tami Thomas
RENAL HISTOLOGICAL CHANGES AFTER RYGB IN A DIET INDUCED OBESE RAT MODEL
- DOI:
10.1016/s0022-5347(09)62013-9 - 发表时间:
2009-04-01 - 期刊:
- 影响因子:
- 作者:
Benjamin K Canales;Saeed R Khan;Patricia A Glenton;Leticia Reyes;Mary K Reinhard;Carolina G Goncalves;Michael M Meguid - 通讯作者:
Michael M Meguid
IS BIOFILM AND MATRIX RELATED? COMPREHENSIVE PROTEOMIC PROFILE OF EARLY URETERAL STENT BIOFILM.
- DOI:
10.1016/s0022-5347(08)61663-8 - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Benjamin K Canales;Lorraine Anderson;LeeAnn Higgins;Manoj Monga - 通讯作者:
Manoj Monga
VIDEO DEMONSTRATION OF ROBOTIC TESTICULAR SPERM EXTRACTION: CRITICAL EVALUATION COMPARED TO OPEN TESE AND PERCUTANEOUS NEEDLE LAVAGE TECHNIQUES IN CANINE MODEL AND THE FIRST HUMAN CASES
- DOI:
10.1016/s0022-5347(08)61064-2 - 发表时间:
2008-04-01 - 期刊:
- 影响因子:
- 作者:
Scott A Polackwich;Patrick Villicana;Carl Bischoff;Bayo Tojuola;Benjamin K Canales;Marc S Cohen;Philipp Dahm;Johannes Vieweg;Sijo J Parekattil - 通讯作者:
Sijo J Parekattil
Benjamin K Canales的其他文献
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{{ truncateString('Benjamin K Canales', 18)}}的其他基金
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 - 财政年份:2020
- 资助金额:
$ 19.81万 - 项目类别:
Non-vitamin D related mechanisms of bone loss after gastric bypass
胃绕道术后骨丢失的非维生素 D 相关机制
- 批准号:
8624117 - 财政年份:2014
- 资助金额:
$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
7957498 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
8631157 - 财政年份:2010
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$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
8536270 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
8319558 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
8146899 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
The Effect of Gastric Bypass Surgery on Renal Function and Metabolism
胃绕道手术对肾功能和代谢的影响
- 批准号:
8721941 - 财政年份:2010
- 资助金额:
$ 19.81万 - 项目类别:
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