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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Ciclesonide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Ciclesonide + placebo<br> | Drug: Ciclesonide<br>* Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)<br>* Other names: Alvesco®;|
| Experimental: Ciclesonide + Vitamin D<br> | Drug: Vitamin D3<br>* vitamin D (100,000 IU loading dose followed by 4,000 IU/day)<br>Drug: Ciclesonide<br>* Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)<br>* Other names: Alvesco®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Failure | Treatment failure is a well-defined asthma outcome reflecting overall asthma control that has been used previously in multiple clinical trials. Treatment failure as defined in the current proposal and prior trials is consistent with the American Thoracic Society (ATS)/European Respiratory Society(ERS) definition of a moderate exacerbation - a deterioration in symptoms and/or lung function with increased rescue bronchodilator use that lasts 2 days or more. The percentages of participants experiencing a treatment failure are Kaplan-Meier estimates of failure rate. | Twenty-eight week intervention period from randomization until end of trial. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung Function Change From Baseline | FEV1 (liters) and methacholine PC20 will be evaluated. Changes are measured as 28 weeks minus baseline. | Change is measured as value at 28 weeks minus baseline value. | 
| Exacerbations | Outcome defined as number of exacerbations per person-year. | Overall exacerbation rate during 28-week trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Vitamin D, Corticosteroids, Treatment failure