Bone In CKD Alkali Response Pilot Trial (BICARb Pilot Trial)

Bone In CKD 碱反应试点试验（BICARb 试点试验）

基本信息

批准号：
10684288
负责人：
Juhi Kumar
金额：
$ 33.41万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684288
关键词：
Acidosis Acids Adult Alkalies Architecture Bicarbonates Biopsy Bone Density Bone Diseases Bone Resorption Bone remodeling C-terminal type I collagen telopeptide Caring Cell Culture Techniques Child Childhood Chronic Chronic Kidney Failure Clinical Trials Cyclophosphamide Data Disease Management Double-Blind Method Dropout Dual-Energy X-Ray Absorptiometry Epidemiology Excretory function Fracture Future General Population Health Impairment Institution Kidney Kidney Diseases Knowledge Life Cycle Stages Measures Mechanics Mediating Medical center Medicine Metabolic acidosis Minerals Morbidity - disease rate Multi-Institutional Clinical Trial N-terminal Nephrolithiasis Nephrology Osteoclasts Osteoporosis Outcome PTH gene Pathogenesis Patients Pediatric Hospitals Peripheral Pharmaceutical Preparations Pilot Projects Placebo Effect Placebos Potassium Procollagen Randomized Renal Osteodystrophy Reporting Research Resolution Resources Safety Serum Severity of illness Skeleton Sodium Sodium Bicarbonate Supplementation Symptoms Testing Therapeutic Therapeutic Agents Time Tissues Universities Urine X-Ray Computed Tomography bisphosphonate bone bone imaging bone loss bone quality bone strength bone turnover circulating biomarkers density design efficacy evaluation experience improved innovation microCT mortality nephrotoxicity pediatric patients pharmacologic pilot trial potassium citrate randomized placebo controlled trial randomized, clinical trials response skeletal success treatment group urinary western diet

项目摘要

Abstract Chronic kidney disease (CKD) is a state of impaired bone quality and strength. Renal osteodystrophy (ROD), a global disorder of bone strength, is present in the vast majority of CKD patients. Fracture rates are 2- to 14-fold greater in patients with than without CKD and increase in parallel with CKD severity. CKD in children significantly impairs bone architecture and strength at a time that is critical for developing healthy bones. Fracture rates are 2-3 times higher in children with CKD than the general population. The attendant morbidity and mortality associated with fractures in CKD has led to efforts to better understand their pathogenesis in order to develop and study treatments that improve bone strength while simultaneously providing an acceptable safety profile across the life-course. The lack of safe and proven anti- fracture pharmacologic strategies in children and adults with CKD represents a fundamental therapeutic gap in CKD management. We propose a pilot, 6-month, randomized clinical trial in 15 children and 88 adults with CKD stages 2 and 3 to test potassium citrate supplementation vs. placebo effects on bone strength as measured by high resolution peripheral quantitative computed tomography (HR-pQCT). We will also examine urinary net acid excretion and measures of bone turnover to understand how potassium citrate effects skeletal health. These aims will be achieved through the collaborative efforts of three institutions: Montefiore Medical Center/ Children’s Hospital at Montefiore, Weill Cornell Medicine and Columbia University Irving Medical Center. The research team has the necessary expertise and resources to carry out this clinical trial. This study is innovative, as potassium citrate has never been tested in a randomized, placebo-controlled trial in chronic kidney disease in children and adults. Bone disease in pediatric kidney disease is understudied and this study will be an important first step to evaluating potassium citrate as a therapeutic agent. This pilot study will provide important information for design of a future larger U01 trial to evaluate effects of potassium citrate on bone outcomes across the life-course.

抽象的慢性肾病（CKD）是一种骨质量和肾强度受损的状态。骨营养不良 (ROD) 是一种整体性骨强度紊乱，存在于绝大多数 CKD 患者中患有 CKD 的患者骨折率比未患有 CKD 的患者高 2 至 14 倍，并且还会增加。与儿童 CKD 的严重程度平行，骨骼结构也会受到显着损害。对骨骼健康至关重要的时期的强度是骨折率的 2-3 倍。 CKD 儿童的发病率和死亡率高于一般人群。与 CKD 骨折相关的疾病导致人们努力更好地了解其发病机制为了开发和研究同时提高骨强度的治疗方法在整个生命过程中提供可接受的安全性缺乏安全且经过验证的抗病毒药物。患有 CKD 的儿童和成人的骨折药理学策略是一个基本的策略 CKD 管理中的治疗差距。我们提议对 15 名患有 CKD 的儿童和 88 名成人进行为期 6 个月的随机临床试验第 2 和第 3 阶段测试补充柠檬酸钾与安慰剂对骨强度的影响通过高分辨率外周定量计算机断层扫描 (HR-pQCT) 测量。还将检查尿净酸排泄和骨转换测量，以了解如何柠檬酸钾影响骨骼健康。这些目标将通过三个机构的合作努力来实现：蒙蒂菲奥里、威尔康奈尔医学院和哥伦比亚医疗中心/儿童医院大学欧文医学中心。研究团队拥有必要的专业知识和资源。进行这项临床试验是创新的，因为柠檬酸钾从未经过测试。在一项针对儿童和成人慢性肾病的随机、安慰剂对照试验中。儿童肾脏疾病的疾病正在得到充分研究，这项研究将是重要的第一步这项初步研究将为评估柠檬酸钾作为治疗剂提供重要依据。设计未来更大规模的 U01 试验的信息，以评估柠檬酸钾对骨骼的影响整个生命过程的结果。