Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers

Phase 3

Completed

• Conditions: Asthma; Asthma Exacerbations; Preschool Child; Vitamin D; Upper Respiratory Infection; Randomized Controlled Study; Symptoms; Bronchodilator Agents

• Registration Number: NCT03365687
• Lead Sponsor: Professor Francine Ducharme

Brief Summary

In this 7-month randomized controlled trial, children aged 1 to less than 6 years, with recurrent 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, and a daily supplement of vitamin D or a placebo. This study will test whether children in vitamin D group 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

This is a multicenter triple-blind randomized parallel-group, placebo-controlled trial of vitamin D3 supplementation. Children aged 1-5 (\<6) years with physician-diagnosed asthma predominantly triggered by upper respiratory tract infections will be screened for enrolment in paediatric asthma, respiratory or allergy clinics and the ED departments and randomized between Sept 1 to January 31, annually (4 recruitment years) and year around from 2022 onwards.

Using a computer-generated random list, stratified by site, children will be allocated (1:1) using permuted block randomisation method to enhance concealment.

Children will be followed for 7 months, with 3 visits every 3.5 months with repeated urine (for calcium:creatinine ratio) and blood samples. In addition, ten (10) days after each bolus, urine will be sampled for urinary calcium:creatinine ratio. In case of elevated urine calcium:creatinine ratio, a blood sample may be needed primarily for markers of calcium metabolism and exploratory outcomes. Only patients enrolled at CHU Sainte-Justine and Montreal Children's Hospital will receive a systematic home visit 10 days after first bolus for both urine and blood samples. There will be 6 follow-up phone calls, at week 1 and then monthly, to inquire about exacerbations and URTIs, remind parents to complete questionnaires and to collect a nasal swab at each exacerbation and screen for adverse events.

The main outcome is the number of courses of rescue oral corticosteroids (OCS) per child during the study period. Several secondary outcomes will be documented using biological samples and validated questionnaires to ascertain laboratory-confirmed respiratory infections, intensity and severity of exacerbations, mean number of ED visits, parents' functional status during exacerbations, de-intensification of preventive asthma therapy, cost effectiveness, and safety profile.

A sample of 432 children (400+7,5% attrition) per arm will provide 80% power with a two-tailed alpha of 5% to detect a 25% relative reduction in the mean number of exacerbations requiring OCS per child.

An intention-to-treat (ITT) analysis will be carried out with all randomised children.

Study Timeline

• Study First Submitted: 2017-12-03
• Study First Submitted QC: 2017-12-03
• Study First Posted: 2017-12-07
• Study Start: 2018-10-01
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-28
• Last Update Posted: 2025-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 323

Inclusion Criteria

• Age 1-5 years
• Physician-diagnosed asthma (as per the 2015 Canadian Position Paper on the diagnosis of preschool asthma)
• ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months; or from the pandemic (2020) onwards, ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 12 months (as documented by pharmacy/medical records)
• ≥4 upper respiratory tract infections (URTIs) in the past 12 months (as per parental report); or from the pandemic (2020) onwards, ≥ 2 URTIs in past 12 months
• URTIs as the main asthma trigger (as per parental report)

Exclusion Criteria

• Intake > 400 IU/day of vitamin D3 supplements or fish oil in the past 3 months
• Intention to use > 400 IU/day of vitamin D3 supplements or fish oil in the fall and winter
• Extreme prematurity (< 28 week gestation)
• No vitamin D supplementation (if breast-fed in the last 6 months)
• Vitamin D restrictive diets, that is, minimal intake of vitamin D fortified milk (<250 mL/day for 1-3 years or <375 mL/day for 4-6 years AND no other (or <200 IU/day) vitamin D supplement
• Recent immigrants from regions at high risk of rickets (in the past 12 months)
• Recent refugees (in the past 12 months)
• Undernourished children
• Other chronic respiratory disease (e.g. Cystic fibrosis, Bronchopulmonary dysplasia) or chronic kidney, gastrointestinal, endocrinological or cardiac diseases, or sickle cell anemia
• History of bone disorder disease (e.g. rickets, osteomalacia)
• Intake of oral anti-epileptic, diuretic or anti-fungal medications
• Anticipated difficulty with follow-up or with adherence to the intervention or the procedures

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of asthma exacerbations per child treated with rescue oral corticosteroids	7 months	Group difference in the mean number of exacerbations treated with rescue oral corticosteroids/child

Secondary Outcome Measures

Name	Time	Method
Laboratory-confirmed respiratory infections	7 months	Group difference in (i) mean number of laboratory-confirmed respiratory infections per child and (ii) distribution of viruses during colds and/or asthma exacerbations
Mean number of ED visits and hospital admissions for asthma exacerbations	7 months	Group difference in mean number of ED visits and hospital admissions for asthma exacerbations per child
De-intensification of preventive asthma therapy	3.5 and 7 months	Group difference in proportion of children with de-intensification of preventive asthma therapy
Duration of asthma symptoms during asthma exacerbations	7 months	Group difference in the mean duration of symptoms during asthma exacerbations per child (i) documented in writing on the validated 'Asthma Flare-up Diary for Young Children' and (ii) reported verbally by parents,
Duration of B2-agonist use during asthma exacerbations	7 months	Group difference in the mean duration of B2-agonist use during asthma exacerbations per child (i) documented in writing on the validated 'Asthma Flare-up Diary for Young Children' and (ii) reported verbally by parents,
Severity of asthma symptoms during asthma exacerbations	7 months	Group difference in the severity of symptoms during asthma exacerbations per child documented on the 'Asthma Flare-up Diary for Young Children'
Intensity of use of rescue β2-agonists during asthma exacerbations	7 months	Group difference in the mean cumulative use of rescue β2-agonists per child during exacerbations documented on the validated 'Asthma Flare-up Diary for Young Children'
Parents' functional status during asthma exacerbations	7 months	Group difference in the mean parents' functional status during asthma exacerbations per child as documented on the validated 'Effect of a child's asthma flare-up on parents questionnaire'
Number of parental workdays lost	7 months	Group difference in the cumulative number of days of work or regular planned activities missed by parents to care for their child during asthma exacerbations
Parental productivity	7 months	Group difference in the extent to which parents were able to perform their work or regular planned activities during their child's acute asthma exacerbation (%)
Intervention cost-effectiveness	7 months	Cost of intervention vs. cost (family expenses and health care) of exacerbations

Trial Locations

Locations (9)

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Children's Hospital of London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Montreal Children's Hospital; 🇨🇦 Montreal, Quebec, Canada

CHU Sainte Justine; 🇨🇦 Montreal, Quebec, Canada

Maisonneuve-Rosemont Hospital; 🇨🇦 Montreal, Quebec, Canada

CHU de Québec-Université Laval; 🇨🇦 Québec, Quebec, Canada

CHU de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada