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）： 这项 2 期临床试验将确定每月口服维生素 D 是否可以降低镰状细胞病儿童出现呼吸道并发症的风险。越来越多的证据表明，维生素 D 除了在钙和骨骼稳态中发挥作用外，还是先天性和适应性免疫反应的多功能调节剂。维生素 D 含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。镰状细胞病是一种罕见疾病，在美国影响约 89,000 人，是一种遗传性红细胞疾病，具有急性血管闭塞并发症以及微血管闭塞、溶血引起的内皮功能障碍和血管病变导致的慢性多器官损伤。儿童早期因镰状细胞诱发的梗塞而导致的功能性无脾会损害免疫防御。呼吸系统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。由于阳光照射有限、肤色较深和营养不良，镰状细胞病患者缺乏维生素 D 的风险很高。维生素 D 具有有效的抗菌和免疫调节特性，可能有助于预防镰状细胞病引起的呼吸道并发症。该项目是一项为期 2 年的对照、双盲、随机 2 期临床试验，比较每月一次口服维生素 D3（100,000 IU（2.5 毫克））与每月一次标准剂量口服维生素 D3（12,000 IU（0.3 毫克））在降低 80 名 3 至 20 岁镰状细胞病儿童和青少年呼吸系统事件发生率方面的功效。 该试验有三个具体目标：(1) 确定患有镰状细胞病的儿童和青少年每月口服维生素 D3（100,000 IU [2.5 mg]）是否会降低呼吸系统事件（定义为呼吸道感染、哮喘恶化和急性胸部综合征发作）的发生率； (2)评价每月口服维生素D3对肺功能、气道高反应性和气道炎症的影响； (3) 使用 T 细胞效应器和调节功能以及全身炎症指标来检查每月口服维生素 D3 对免疫功能的影响。