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.

摘要 慢性肾脏病（CKD）是一种骨质和强度受损的状态。肾 骨营养不良（ROD）是一种全球性骨强度紊乱，存在于绝大多数CKD中 患者CKD患者的骨折发生率是非CKD患者的2- 14倍， 与CKD严重程度平行。儿童CKD显著损害骨结构， 这对骨骼健康至关重要。骨折率是 CKD儿童的发病率高于一般人群。随之而来的发病率和死亡率 与CKD骨折相关的研究已经导致人们努力更好地了解其发病机制， 为了开发和研究治疗方法，提高骨强度，同时 在整个生命过程中提供可接受的安全性。缺乏安全可靠的抗- CKD儿童和成人的骨折药理学策略代表了一种基本的 CKD管理中的治疗差距。 我们建议在15名儿童和88名成人CKD患者中进行一项为期6个月的试点随机临床试验 阶段2和阶段3，测试柠檬酸钾补充剂与安慰剂对骨强度的影响 通过高分辨率外周定量计算机断层扫描（HR-pQCT）测量。我们 还将检查尿净酸排泄和骨转换的措施，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实现： 医疗中心/Montefiore儿童医院、Weill Cornell Medicine和哥伦比亚 欧文大学医学中心。研究团队拥有必要的专业知识和资源 进行这项临床试验这项研究是创新的，因为柠檬酸钾从未被测试过 在一项针对儿童和成人慢性肾脏疾病的随机、安慰剂对照试验中，骨 儿童肾脏疾病的研究不足，这项研究将是重要的第一步 评估柠檬酸钾作为治疗剂。这项试点研究将提供重要 用于设计未来更大规模U 01试验以评价柠檬酸钾对骨影响的信息 整个生命过程的结果。