Impact of two oral doses of 100,000 IU of vitamin D(3) in preschoolers with viral-induced asthma: a pilot randomised controlled trial

BACKGROUND: New evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D(3) in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes. METHODS: We conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1–5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D(3) (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (Δ25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD ≥ 75 nmol/L, safety, and adverse event rates. RESULTS: Children (N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the Δ25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time (p < 0.0001) and group*time interaction effect (p < 0.0001), in favour of the intervention. A significant group difference in the Δ25OHD was observed 10 days after the first (119.3 [105.8, 132.9] nmol/L) and second (100.1 [85.7, 114.6] nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (≥ 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child. CONCLUSION: Two oral boluses of 100,000 IU vitamin D(3,)once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD ≥ 75 nmol/L throughout 7 months in only slightly more than half of participants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-019-3184-z) contains supplementary material, which is available to authorized users.