Protocol for the Vitamin D Oral Replacement in Asthma (VDORA) study

Obesity and asthma are epidemic in the United States and obesity is an independent risk factor for asthma. Low vitamin D levels (i.e. serum 25-hydroxyvitamin D) have been reported in patients with reduced lung function, more frequent respiratory infections, and asthma exacerbations. Experts have proposed that serum levels > 40 ng/mL are required to offer the immunomodulatory benefits of vitamin D. Low vitamin D levels are common in both obesity and asthma, but it is not known whether supplementation with vitamin D improves asthma symptoms. Guidance for drug development stresses the importance of early phase studies to establish accurate population pharmacokinetics (PK) and drug dosing prior to larger phase 3 trials. The PK of this fat-soluble vitamin in children with increased adiposity are unknown; as are the doses need to reach proposed immunomodulatory levels. The objective of this study is to characterize the PK of vitamin D in children with obesity. Children ages 6--18 years who had physician diagnosed asthma and a body mass index (BMI) >85th percentile will be randomized to receive either standard daily dosing or loading doses followed by standard daily dosing. Blood samples will be obtained to characterize the PK of vitamin D. The results of this study will be used to identify a sufficient dose of vitamin D supplement to raise serum levels above a pre-specified value that may result in anti-inflammatory actions that could improve asthma symptoms.