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

维生素 D 治疗镰状细胞 D 呼吸道并发症的二期研究

• 批准号: 8165593
• 负责人: Gary M Brittenham
• 金额: $ 40万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8165593
• 关键词: Ph; Study; Vitamin; Tx; Respiratory

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.

描述（由申请人提供）： 该阶段2临床试验将确定每月口服维生素D是否可以降低镰状细胞疾病儿童呼吸并发症的风险。积累的证据表明，维生素D除了其在钙和骨骼稳态中的作用外，是先天性和适应性免疫反应的多功能调节剂。维生素D量不足已与肺功能受损以及呼吸道感染和哮喘的风险增加有关。镰状细胞疾病是一种影响美国估计有89,000人的孤儿疾病，是一种遗传性的红细胞疾病，患有急性血管 - 易感性并发症和微血管闭塞导致的慢性多器官损害，血液溶解诱导的内皮功能障碍和血管病。儿童早期的疾病引起的梗塞引起的功能性浮游生会损害免疫防御能力。呼吸并发症是发病率和镰状细胞疾病死亡的主要原因。对感染的敏感性增加和炎症反应增强是疾病中肺部疾病发病机理的关键组成部分。镰状细胞疾病的患者由于暴露有限，深色肤色和营养不良而导致维生素D缺乏症的风险很高。维生素D具有有效的抗菌和免疫调节特性，可帮助预防镰状细胞疾病的呼吸并发症。该项目是一项为期2年的受控，双盲，随机2阶段2临床试验，比较了口服维生素D3，每月一次100,000 IU（2.5 mg）的疗效，标准剂量口服维生素D3，12,000 IU（0.3 mg）每月给予一次，以减少80名儿童呼吸疾病的发生率，以降低80岁儿童的呼吸疾病和3岁，3至20岁。 该试验具有三个特定的目的：（1）确定给患有镰状细胞疾病的儿童和青少年的每月口服维生素D3（100,000 IU [2.5 mg]）是否会降低呼吸道事件的速度，该呼吸道事件的速度定义为呼吸道感染，呼吸道感染，呼吸症和急性胸部胸部胸腔综合征的发作； （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的影响； （3）使用T细胞效应子和调节功能的测量以及全身性炎症的测量，检查每月口服维生素D3对免疫功能的影响。