Vitamin D in Preschoolers With Viral-induced Asthma

Study Overview
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Brief Summary
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In this 7-month randomized controlled trial, children aged 1-6 years with asthma attacks triggered mostly by colds, will receive a high dose of vitamin D or a placebo every 3.5 months during their usual clinic visit. This study will test whether children receiving a high dose of vitamin D have less frequent and less severe asthma exacerbations compared with those receiving placebo.The study will also document the safety profile of this strategy.

Detailed Description
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IMPORTANT NOTE: Due to receiving a 2-year partial funding enabling only a single-centre pilot trial, rather than an adequately-powered multicentre study, the primary outcome was modified post hoc for the overall change from baseline in total serum 25OHD during the study as well as at 3.5 and 7 months, similar to our previous pilot study.(NCT01999907) Post hoc secondary outcomes included the group difference in the proportion of children with total 25OHD ≥75 nmol/L at 3.5 and 7 months and in the rate of oral corticosteroid courses per child. Other a priory specified outcomes included the proportion of children with hypercalciuria (Ca:Cr) >1.25 (1-2 years), >1 (2-5 years) nmol/nmol at any point in time; proportion of children with ≥1 exacerbation requiring rescue oral steroids (former primary outcome); number of emergency department (ED) visits; intensity and duration of asthma symptoms and cumulative use of rescue ß2-agonist use, documented on Asthma Flare-up Diary for Young Children (ADYC); the impact of parents' functional status during exacerbations ascertained on the Effect of a child's asthma flare-up on parents; and duration of URTI. Based on this analysis of this new post-hoc primary outcome, we have changed the intervention and the primary outcome and obtained funding for a new large multicentre study NCT03365687. it is thus important to share the results of this current trial with other investigators PRIOR REPORTED DESCRIPTION Design: A multicenter triple-blind randomized parallel-group, placebo-controlled trial of vitamin D3 supplementation. Children aged 1-5 years with (i) physician-diagnosed asthma, predominantly triggered by upper respiratory tract infections (URTIs), (ii) ≥4 reported URTIs in the past year, and (iii) ≥1 exacerbation requiring OCS (a recognised marker of moderate and severe exacerbations) in the past 6 months or ≥2 in the past 12 months, will be randomly allocated to one of two treatments in blocks of 4-6, stratified on recruitment site: Intervention group (n=432)-100,000 IU oral vitamin D3; control group (n=432)-identical placebo, for 2 oral doses, 3.5 months apart. Co-intervention with asthma therapy (preventive or pre-emptive ICS) will be left to the discretion of the physician and documented. Children will be followed every 3.5 months as per usual practice, with a home visit 10 days after each bolus, during which urine and blood will be sampled for urinary calcium:creatinine ratio, serum vitamin D, markers of calcium metabolism, and mechanistic exploration. A validated diary will serve to document the intensity and severity of exacerbations. In two sites, preschool lung function will be documented (if ≥ 3yrs). Outcomes: Primary endpoint-number of exacerbations requiring rescue oral corticosteroids (OCS) per child, documented by medical and pharmacy records. Secondary outcomes: duration and severity of exacerbations (symptoms & β2-agonist use, by diary; emergency visits, by medical records), parental functional status (by validated instrument), asthma therapy intensification and health care and direct costs (by health records & parent reports). Safety, mechanistic, exploratory outcomes: hypercalciuria, calcium metabolism, excess vitamin D, change in serum gene expression at 10 days (first 25 patients); and change from baseline at 7 months in preschool lung function (2 sites). Based on 3 published RCTs, a sample of 432 per arm (400+7.5% attrition) will provide 80% power (2-tailed alpha of 5%) to detect a 25% reduction in number of exacerbations requiring OCS/child (0.55 vs. 0.4125).

Official Title
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Vitamin D In the Prevention of Viral-induced Asthma of Preschoolers: a Randomised Controlled Trial (RCT)- (DIVA)

Conditions
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Asthma

Intervention / Treatment
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* Dietary Supplement: vitamin D
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 1-5 years physician-diagnosed asthma as per the Global Initiative for Asthma (GINA) guidelines URTIs as the main asthma trigger (parental report) ≥4 URTIs in the past 12 months (parental report) ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months Exclusion Criteria: intake or intention to use more than 400 IU/day of vitamin D supplement extreme prematurity (<28 weeks gestation) infants <12 months of age no vitamin D supplementation when breast-fed recent (<1 year) immigrants from a region at high risk of rickets children with vitamin D restrictive diets e.g. vegans other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis) condition(s) that alter calcium or vitamin D metabolism/absorption (hypo/hyperparathyroidism, kidney/liver disease, inflammatory bowel disease) medications that interfere with vitamin D metabolism (anti-epileptics, diuretics, antacids, anti-fungal drug) vitamin D supplementation >1000 IU/ day in last 3 months anticipated difficult follow-up (unable to attend clinic visits; plan to leave the province).

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 5 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>2 ml identical placebo taken by mouth at baseline and 3.5 months. | Dietary Supplement: placebo<br>* Two doses of identical placebo (2 mL) given 3.5 months part, once in the fall, once in the winter<br>|
| Active Comparator: Vitamin D<br>Vitamin D (100,000IU) given in a 2 ml oral dose at baseline and 3.5months. | Dietary Supplement: vitamin D<br>* Two doses of cholecalciferol 100,000 unit (2 mL) given 3.5 months apart, once in the fall, once in the winter<br>* Other names: cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum 25OHD | Group difference in the adjusted change from baseline 25OHD over time and specifically at 3.5 and 7 months | During the 7-month follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with total 25OHD ≥75 nmol/L | Group difference in the proportion of children with total 25OHD ≥75 nmol/L | at 3.5 and 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCT, asthma, pediatric, virus, corticosteroid