Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers
- Conditions
- Asthma
- Interventions
- Dietary Supplement: PlaceboDietary Supplement: Vitamin D
- 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 infection 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).
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 323
- 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 (as documented by pharmacy/medical records)
- ≥4 upper respiratory tract infections (URTIs) in the past 12 months (as per parental report)
- URTIs as the main asthma trigger (as per parental report)
- 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
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo orally at baseline and at 3.5 months with daily placebo during 7 months Vitamin D Vitamin D Vitamin D supplement (100,000 IU) orally at baseline and at 3.5 months with daily 400 IU vitamin D for 7 months
- 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 Duration of asthma symptoms during asthma exacerbations 7 months Group difference in the mean duration of asthma symptoms documented on the validated 'Asthma Flare-up Diary for Young Children'
Mean number of ED visits for asthma exacerbations 7 months Group difference in mean number of ED visits for asthma exacerbations
Intervention cost-effectiveness 7 months Cost of intervention vs. cost (family expenses and health care) of exacerbations
Laboratory-confirmed respiratory infections 7 months Group difference in mean number of laboratory-confirmed respiratory infections during asthma exacerbations
De-intensification of preventive asthma therapy 7 months Group difference in proportion of children with de-intensification of preventive asthma therapy
Severity of asthma symptoms during asthma exacerbations 7 months Group difference in the mean severity of asthma symptoms 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 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 exacerbation as documented on the validated 'Effect of a child's asthma flare-up on parents questionnaire'
Trial Locations
- Locations (9)
Children's Hospital of London Health Sciences Centre
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Maisonneuve-Rosemont Hospital
🇨🇦Montreal, Quebec, Canada
CHU Sainte Justine
🇨🇦Montreal, Quebec, Canada
CHU de Québec-Université Laval
🇨🇦Québec, Quebec, Canada
CHU de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada