Vitamin D in Preschoolers With Viral-induced Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2/Phase 3

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).
    

Intervention name(s): vitamin D; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Two doses of cholecalciferol 100,000 unit (2 mL) given 3.5 months apart, once in the fall, once in the winter; Two doses of identical placebo (2 mL) given 3.5 months part, once in the fall, once in the winter
Other intervention name(s): cholecalciferol
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: RCT; asthma; pediatric; virus; corticosteroid