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

描述(由申请人提供)： 这项第二阶段临床试验将确定每月口服维生素D是否可以降低患有镰状细胞疾病的儿童的呼吸道并发症的风险。越来越多的证据表明，维生素D除了在钙和骨骼动态平衡中的作用外，还是一种天然免疫和获得性免疫反应的多功能调节剂。维生素D摄入量不足与肺功能受损以及呼吸道感染和哮喘风险增加有关。镰状细胞病是一种孤儿疾病，在美国估计有89,000人受到影响，是一种遗传性红细胞疾病，具有急性血管闭塞并发症和慢性多器官损伤，原因是微血管闭塞、溶血导致的内皮功能障碍和血管病变。儿童早期因镰刀引起的脑梗塞所致的功能性脾功能不全会损害免疫防御。呼吸道并发症是镰状细胞病发病和死亡的主要原因。对感染的易感性增加和炎症反应增强是镰状病肺部疾病发病机制的关键组成部分。镰状细胞病患者由于有限的阳光暴露、深色肤色和营养不良，面临维生素D缺乏症的高风险。维生素D具有强大的抗菌和免疫调节特性，可能有助于预防镰状细胞病的呼吸道并发症。该项目是一项为期两年的对照、双盲、随机的第二阶段临床试验，比较每月服用一次10万国际单位(2.5毫克)的口服维生素D3与每月服用一次标准剂量的12,000国际单位(0.3毫克)维生素D3在降低80名患有镰状细胞疾病的3至20岁儿童和青少年的呼吸系统事件发生率方面的疗效。这项试验有三个具体目标：(1)确定每月口服维生素D3(10万国际单位[2.5毫克])给患有镰状细胞疾病的儿童和青少年是否将减少呼吸道事件的发生率，这些事件被定义为呼吸道感染、哮喘加重和急性胸部综合征的发作；(2)评估每月口服维生素D3对肺功能、呼吸道高反应性和呼吸道炎症的影响；以及(3)通过T细胞效应和调节功能以及全身炎症的测量，检查每月口服维生素D3对免疫功能的影响。

DESCRIPTION (provided by applicant): 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 both innate and adaptive immune responses. Inadequate amounts of vitamin D have been linked to impaired lung function and an increased risk of respiratory infections and asthma. Sickle-cell disease, an orphan disease affecting an estimated 89,000 individuals in the United States, is an inherited red blood cell disorder with acute vaso-occlusive complications and chronic multi-organ damage resulting from microvascular occlusion, 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. Patients with sickle-cell disease are at a high risk for vitamin D deficiency due to limited sun exposure, dark skin color and poor nutrition. 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 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.