Vitamin D and Severe Asthma Exacerbations

Study Overview
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Brief Summary
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This study of vitamin D is designed to assess both the safety and efficacy of potential doses (2,000 IU/day and 4,000 IU/day) in raising a vitamin D level to a normal range in a short period of time (e.g. 4 weeks or less) compared to 200 IU/day. In children with vitamin D insufficiency or deficiency who are at risk for severe asthma exacerbations, we hypothesize that both vitamin D supplementation with 4,000 IU/day and 2,000 IU/day will safely achieve normal vitamin D levels, but that the higher dose (4,000 IU/day) will result in a larger proportion of subjects achieving this level at 4 and 8 weeks.

Detailed Description
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Asthma is a major public health problem in the United States and worldwide. Severe disease exacerbations account for the majority of costs attributable to asthma in the United States. Vitamin D is an essential nutrient with significant immuno-modulatory effects. The observation that vitamin D insufficiency and asthma share risk factors such as urban residence, obesity, and African American ethnicity has generated significant interest in exploring a link between these two conditions. This is an 8-week randomized, double-masked, controlled trial of vitamin D3 (2,000 IU/day and 4,000 IU/day) to achieve vitamin D sufficiency (a serum 25(OH)D ≥30 ng/ml in 60 school-aged children (ages 6 to 14 years) who have vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) and are at risk for severe asthma exacerbations, but whose asthma that is well-controlled on medium-dose inhaled corticosteroid (ICS) at the end of a 4-week run-in period.

Official Title
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A Phase I Trial for Children With Vitamin D Insufficiency and High Risk of Severe Asthma Exacerbations

Conditions
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Asthma

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 6 years of age and younger than 15 years of age Have physician-diagnosed asthma Taking a medium dose of ICS (e.g. fluticasone 220mcg BID) for daily asthma control for at least 6 months in the prior year. Have had a severe asthma exacerbation in the previous year, defined as an Emergency Department (ED) visit, hospitalization, or unscheduled clinic visit for asthma resulting in intramuscular, intravenous, or oral steroids. Have bronchodilator responsiveness (BDR, an increase in FEV1 ≥12% from baseline after administration of inhaled albuterol) or (if no BDR) increased airway responsiveness to methacholine challenge Have vitamin D insufficiency (a serum vitamin D (25(OH)D) level <30 ng/ml) Have his/her parents give voluntary written consent to participate in the study Exclusion Criteria: Chronic respiratory disorder other than asthma (e.g., bronchiectasis). Severe asthma, as evidenced by any of the following: a) chronic need for medication other than single controller therapy and inhaled β2-agonist, b) intubation for asthma at any time, and c) ≥2 hospitalizations or ≥6 severe asthma exacerbations in the previous year History of cigarette smoking in the prior year or former smoking if ≥5 pack-years Hepatic or renal disease, metabolic rickets, malabsorptive disorders, or other chronic diseases that would affect vitamin D metabolism Immune deficiency, cleft palate or Down's syndrome, which might increase the child's likelihood of respiratory infections Treatment with anticonvulsants or pharmacological doses of vitamin D (≥1,000 IU/day of vitamin D2 or D3) Chronic oral corticosteroid therapy Inability to perform acceptable spirometry Use of investigational therapies or participation in clinical trials 30 days before or during the duration of the study Serum calcium >10.8 mg/dl Serum 25(OH) D <10 ng/ml (severe vitamin D deficiency)

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 14 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholecalciferol 4000 IU<br>Cholecalciferol 4000 IU oral chewable tablet once daily for 8 weeks | Dietary Supplement: Cholecalciferol<br>* vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.<br>* Other names: vitamin D3;|
| Experimental: Cholecalciferol 2000 IU<br>Cholecalciferol 2000 IU oral chewable tablet once daily for 8 weeks | Dietary Supplement: Cholecalciferol<br>* vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.<br>* Other names: vitamin D3;|
| Active Comparator: Cholecalciferol 200 IU<br>Cholecalciferol 200 IU oral chewable tablet once daily for 8 weeks | Dietary Supplement: Cholecalciferol<br>* vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.<br>* Other names: vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation | The primary outcome of the proposed trial will be a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation | 8 weeks | 
| Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation | The outcome is defined as the number of participants with a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Vitamin D Toxicity | Participants with vitamin D toxicity, hypercalcemia (>10.8mg/dl) and/or an elevated urine Ca/Cr ratio (>0.37) | 8 weeks | 
| Number of Participants With Elevated Urinary Calcium/Creatinine Ratio | Elevated urinary calcium/creatinine ratio defined as UCa/UCr > 0.37 after either 4 weeks or 8 weeks of supplementation | 4 and/or 8 weeks | 
| Number of Participants With FEV1 < 80% of Predicted | Forced expiratory volume in 1 second (FEV1) as percent predicted (with reference values used according to the child's age, gender and ethnicity). | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, vitamin D