Clinical trial NCT02197702: Vitamin D in Preschoolers With Viral-induced Asthma
Official title: Vitamin D In the Prevention of Viral-induced Asthma of Preschoolers: a Randomised Controlled Trial (RCT)- (DIVA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Asthma
Keywords: RCT
asthma
pediatric
virus
corticosteroid
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: The Hospital for Sick Children
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
name: Montreal Children's Hospital of the MUHC
name: British Columbia Children's Hospital
name: London Health Sciences Centre
First posted: 2014-07-23
Enrollment: 47
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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).

Primary outcomes:
measure: Change From Baseline in Serum 25OHD
timeFrame: During the 7-month follow-up period
Secondary outcomes:
measure: Number of Participants With Total 25OHD ≥75 Nmol/L
timeFrame: at 3.5 and 7 months
measure: Emergency Department Visit for an Asthma Flare-up
timeFrame: During the 7-month follow-up period
Other outcomes:
measure: Hypercalciuria
timeFrame: At any point during the 7-month follow-up period
measure: Elevated Serum 25-hydroxyvitamin D (25OHD)
timeFrame: At any point during the 7-month follow-up period
measure: Perturbation of the Calcium Homeostasis
timeFrame: At any point during the 7-month follow-up period
measure: Number of URTIs (Verbal Report)
timeFrame: During the 7-month follow-up period
measure: Viral Upper Respiratory Tract Infections (URTI)
timeFrame: During the 7-month follow-up period
measure: Rescue β2-agonist Use During an Asthma Flare-up (Standardized Over 7 Days)
timeFrame: During the 7-month follow-up period
measure: Severity of Asthma Symptoms During an Asthma Flare-up (Cumulative Daily Score Standardized Over 7 Days)
timeFrame: During an URTI or flare-up during the 7-month follow-up period
measure: Duration of Asthma Symptoms During a Flare-up (by Diary)
timeFrame: During an URTI or flare-up during the 7-month follow-up period
measure: Number of Asthma Exacerbations/Child
timeFrame: During the 7-month follow-up period
measure: Impact of Exacerbations on Caregivers' Functional Status
timeFrame: During an URTI or flare-up during the 7-month follow-up period
measure: Caregivers' Workday Lost (in Days Per Flare-up)
timeFrame: During an URTI or flare-up during the 7-month follow-up period
measure: Percent of Participants With at Least 1 Exacerbation Requiring Rescue Oral Corticosteroids
timeFrame: During the 7-month follow-up period
measure: Duration of Asthma Symptoms During a Flare-up (Verbal Report)
timeFrame: During an URTI or flare-up during the 7-month follow-up period
Locations:
city: Montreal
country: Canada
facility: CHU Sainte Justine
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Francine M Ducharme, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ducharme FM, Jensen M, Mailhot G, Alos N, White J, Rousseau E, Tse SM, Khamessan A, Vinet B. Impact of two oral doses of 100,000 IU of vitamin D3 in preschoolers with viral-induced asthma: a pilot randomised controlled trial. Trials. 2019 Feb 18;20(1):138. doi: 10.1186/s13063-019-3184-z.
citation: Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.