Vitamin D in Preschoolers With Viral-induced Asthma

Phase 2

Completed

Conditions: Asthma

Interventions: Dietary Supplement: placebo
Dietary Supplement: vitamin D

Registration Number: NCT02197702

Lead Sponsor: St. Justine's Hospital

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	2 ml identical placebo taken by mouth at baseline and 3.5 months.
Vitamin D	vitamin D	Vitamin D (100,000IU) given in a 2 ml oral dose at baseline and 3.5months.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Serum 25OHD	During the 7-month follow-up period	Group difference in the adjusted change from baseline 25OHD over 7 months

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Total 25OHD ≥75 Nmol/L	at 3.5 and 7 months	Group difference in the number of participants with total 25OHD ≥75 nmol/L
Emergency Department Visit for an Asthma Flare-up	During the 7-month follow-up period	Group difference in the number of emergency department visits for asthma per child