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

Public Health Relevance

Component: Project Relevance This Phase 2 clinical trial will determine if monthly oral vitamin D3, 100,000 IU (2.5 mg), will reduce the risk of respiratory complications in children and adolescents with sickle-cell disease. Demonstration that a monthly dose of vitamin D is efficacious in reducing the risk of respiratory infections, exacerbations of asthma and the acute chest syndrome could help establish a simple and low-cost intervention to reduce morbidity and death in children and adolescents with sickle-cell disease and lead to major changes in the management of their vitamin D status.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZFD1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Schools of Medicine
New York
United States
Zip Code