Ph 2 Study of Vitamin D for Tx of Respiratory Complications in Sickle Cell Ds

4.4.6其他项目信息组成部分：项目概要/摘要 这项2期临床试验将确定每月口服维生素D是否可以降低呼吸道疾病的风险。 镰状细胞病患儿的并发症。越来越多的证据表明，维生素D，除了 它在钙和骨稳态中作用，是先天性和适应性免疫的多功能调节剂 反应和炎症，可以降低呼吸道感染和哮喘恶化的风险， 孩子维生素D的不足与肺功能受损和增加的风险有关。 呼吸道感染和哮喘发作镰状细胞病是一种孤儿病， 在美国有89，000人，是一种遗传性红细胞疾病，伴有急性血管阻塞 微血管闭塞引起的并发症和慢性多器官损伤，溶血诱导 内皮功能障碍和血管病变。早期镰状细胞梗死所致的功能性无脾 儿童期会损害免疫系统。呼吸系统并发症是发病和死亡的主要原因 镰状细胞病感染易感性的增加和炎症反应的增强是至关重要的 镰状病肺部疾病的发病机制的组成部分。地方和国家研究发现， 大多数镰状细胞病患儿的血清25-羟基维生素D水平非常低。维生素d 有效的抗菌和免疫调节特性，可能有助于预防呼吸系统并发症， 镰状细胞病本项目是一项为期2年的对照、双盲、随机2期临床试验， 每月一次口服维生素D3 100，000 IU（2.5 mg）的功效，标准剂量口服维生素D3 12，000 IU（0.3 mg），每月一次，降低80名儿童和青少年的呼吸道事件发生率，3至20 10岁患有镰状细胞病选择每月口服维生素D3的剂量是为了达到 维生素D与呼吸道病毒感染和哮喘恶化易感性降低有关， 不超过生活在阳光充足的环境中的人的水平。这项试验有三个具体目标： (1)确定是否每月口服维生素D3（100，000 IU [2.5 mg]），给予儿童， 青少年镰状细胞病，将降低呼吸道事件的发生率，定义为 呼吸道感染、哮喘恶化和急性胸部综合征发作; (2)评估每月口服维生素D3对肺功能、气道高反应性和 气道炎症;以及 (3)检查每月口服维生素D3对免疫功能的影响，使用T细胞计数， 效应器和调节功能以及系统性炎症

4.4.6 Other Project Information Component: Project Summary/Abstract This Phase 2 clinical trial will determine if monthly oral vitamin D can reduce the risk of respiratory complications in children with sickle-cell disease. Accumulating evidence indicates that vitamin D, in addition to its role in calcium and bone homeostasis, is a multifunctional regulator of innate and adaptive immune responses and of inflammation that can reduce the risk of respiratory infection and asthma exacerbations in children. Inadequate amounts of vitamin D have been linked to impaired lung function and an increased risk of respiratory infections and asthma atacks. Sickle-cell disease, an orphan disease affecting an estimated 89,000 individuals in the United States, is an inherited red blood cel disorder with acute vaso-occlusive complications and chronic multi-organ damage resulting from microvascular oclusion, hemolysis-induced endothelial dysfunction and vasculopathy. Functional asplenia from sickling-induced infarctions during early childhood impairs immune defenses. Respiratory complications are the leading cause of morbidity and of death in sickle-cell disease. Increased susceptibility to infection and a heightened inflammatory response are critical components of the pathogenesis of lung disease in sickling disorders. Local and national studies have found that most children with sickle-cell disease have very low serum 25-hydroxyvitamin D levels. Vitamin D has potent antimicrobial and immunomodulatory properties that may help prevent respiratory complications in sickle-cell disease. This project is a 2-year controlled, double-blind, randomized Phase 2 clinical trial comparing the efficacy of oral vitamin D3, 100,000 IU (2.5 mg) given once a month, with standard-dose oral vitamin D3, 12,000 IU (0.3 mg) given once a month, in reducing the rate of respiratory events in 80 children and adolescents, 3 to 20 years old, with sickle-cell disease. This monthly dose of oral vitamin D3 has been selected to achieve levels of vitamin D associated with decreased susceptibility to respiratory viral infections and asthma exacerbations but to not exceed levels found among individuals living in a sun-rich environment. This trial has three specific aims: (1) to determine whether monthly oral vitamin D3 (100,000 IU [2.5 mg]), given to children and adolescents with sickle-cell disease, will reduce the rate of respiratory events, defined as respiratory infections, exacerbations of asthma, and episodes of the acute chest syndrome; (2) to evaluate the effects of monthly oral vitamin D3 on pulmonary function, airway hyperreactivity and airway inflammation; and (3) to examine the effects of monthly oral vitamin D3 on immune function, using measures of T-cell effector and regulatory function and of systemic inflammation