Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma

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 FEV1 ≥12 % following 180 mcg (4
puffs) levalbuterol at visit 1 OR (b) methacholine 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 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)