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）

• 批准号: 10540003
• 负责人: Juhi Kumar
• 金额: $ 36.85万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/10540003
• 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; Pharmacology; Pilot Projects; Placebo Effect; Placebos; Potassium; Procollagen; Randomized; Randomized Clinical Trials; 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; experience; improved; innovation; microCT; mortality; nephrotoxicity; pediatric patients; pilot trial; potassium citrate; randomized placebo controlled trial; response; skeletal; success; treatment group; urinary; western diet

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 慢性肾脏疾病（CKD）是骨质和力量受损的状态。肾脏 绝大多数CKD中存在骨肌营养不良（ROD）是一种全球骨骼强度障碍 患者。患有CKD的患者的骨折率高2至14倍，并且增加 与CKD严重程度并联。儿童中的CKD极大地损害了骨骼建筑和 强度在发展健康骨骼至关重要的时候。断裂率为2-3次 CKD儿童高于一般人群。随之而来的发病率和死亡率 与CKD中的裂缝相关的已导致努力更好地了解其发病机理 为了开发和研究改善骨骼强度的治疗，同时 在整个生命过程中提供可接受的安全性。缺乏安全且可证明的反 - CKD儿童和成人的断裂药科学策略代表了基本 CKD管理中的治疗差距。 我们提出了15名儿童和88名CKD成人的飞行员，6个月的随机临床试验 第2阶段和第3阶段以测试柠檬酸钾补充剂与安慰剂对骨强度的影响 通过高分辨率外围定量计算机断层扫描（HR-PQCT）测量。我们 还将检查尿NET净酸排泄和骨转换的测量，以了解 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：蒙特菲奥雷 蒙特菲奥尔的医疗中心/儿童医院，威尔·康奈尔医学和哥伦比亚 大学欧文医学中心。研究小组有必要的专业知识和资源 进行这项临床试验。这项研究具有创新性，因为柠檬酸钾从未进行过测试 在一项在儿童和成人的慢性肾脏疾病中的随机，安慰剂对照试验中。骨 小儿肾脏疾病中的疾病被了解，这项研究将是重要的第一步 评估柠檬酸钾作为治疗剂。这项试验研究将提供重要的 设计未来大型U01试验的信息，以评估柠檬酸钾对骨骼的影响 整个生命过程中的结果。