Vitamin D and Severe Asthma Exacerbations

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Cholecalciferol 2000 IU	Cholecalciferol	Cholecalciferol 2000 IU oral chewable tablet once daily for 8 weeks
Cholecalciferol 200 IU	Cholecalciferol	Cholecalciferol 200 IU oral chewable tablet once daily for 8 weeks
Cholecalciferol 4000 IU	Cholecalciferol	Cholecalciferol 4000 IU oral chewable tablet once daily for 8 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

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

Locations (1): Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States