Clinical trial NCT01921894: Vitamin D and Severe Asthma Exacerbations
Official title: A Phase I Trial for Children With Vitamin D Insufficiency and High Risk of Severe Asthma Exacerbations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: asthma
vitamin D
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2013-08-13
Enrollment: 48
Sex: ALL
Minimum age (years): 6
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation
timeFrame: 8 weeks
measure: Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation
timeFrame: 4 weeks
Secondary outcomes:
measure: Number of Participants With Vitamin D Toxicity
timeFrame: 8 weeks
measure: Number of Participants With Elevated Urinary Calcium/Creatinine Ratio
timeFrame: 4 and/or 8 weeks
measure: Number of Participants With FEV1 < 80% of Predicted
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Juan C Celedon, M.D., Dr.P.H.
role: PRINCIPAL_INVESTIGATOR
References: