The purpose of the study is to find out if taking vitamin D in addition to an asthma controller medication helps to prevent worsening of asthma symptoms and asthma attacks.

This is a randomized, double-blind parallel group trial that will enroll individuals who have vitamin D insufficiency and asthma with persistent symptoms despite low-dose inhaled corticosteroid. Participants on low-dose inhaled corticosteroid will be randomized to add-on therapy with either placebo or high-dose vitamin D for a 28-week period. During the inhaled corticosteroid-stable phase, participants will remain on low-dose inhaled corticosteroid. During the inhaled corticosteroid-taper phase, participants will taper their inhaled corticosteroid by 50% at two time-points post-randomization. The investigators will determine if the addition of vitamin D reduces the likelihood of treatment failure when compared to placebo during both the inhaled corticosteroid-stable and inhaled corticosteroid-taper phases of the study. Given the high prevalence of both vitamin D insufficiency and asthma, this trial has high potential to impact daily asthma management.

Inclusion Criteria:

• Men and women 18 years of age and older
• Physician-diagnosed asthma for at least previous 12 months
• Asthma confirmed by: (a) β-agonist reversibility of forced expiratory volume in 1 second (FEV1) ≥12 % following 180 mcg (4 puffs) levalbuterol at visit 1 OR (b) methacholine provocative concentration causing a 20% fall in FEV1 (PC20) ≤ 8 mg/ml if not receiving an inhaled corticosteroid or ≤ 16 mg/ml if receiving an inhaled corticosteroid at visit 2. Source documentation for PC20 from an AsthmaNet methacholine challenge completed within 6 months of visit 2 will be accepted.
• Stable asthma controller therapy (inhaled corticosteroid or leukotriene modifier only) dose for past 2 weeks
• FEV1 ≥ 50% of predicted at visit 1
• Vitamin D level of less than 30 ng/ml at visit 0
• Experienced no more than one treatment failure in the VIDA run-in or oral corticosteroid (OCS) response periods on previous enrollments
• For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method for the duration of the study

Exclusion Criteria:

• Taking vitamin D supplements containing > 1000 IU/day of vitamin D
• Taking >2500 mg/day calcium supplements
• Chronic oral corticosteroid therapy
• Chronic inhaled corticosteroid therapy > 1,000 mcg of fluticasone daily or the equivalent
• History of physician-diagnosed nephrolithiasis
• Use of concomitant medications that alter vitamin D metabolism - phenytoin, phenobarbital, cardiac glycosides; or absorption - orlistat, cholestyramine, colestipol; or those that interfere with study endpoints
• Impaired renal function (GFR < 30 ml/min)
• Asthma exacerbation within past 4 weeks requiring systemic corticosteroids
• Respiratory tract infection within past 4 weeks
• Chronic diseases (other than asthma)
• History of cigarette smoking within the past 1 year or > 10 pack years total
• Serum calcium greater than 10.2 mg/dl on entry
• Urine calcium/creatinine ratio greater than 0.37 (urinary Ca and Creat in mg)