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

Asthma Clinical Trial

— DIVA  

Official title:

Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers: a Randomized Controlled Multicenter Trial (DIVA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03365687
• Other study ID #: MP-21-2018-1657
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: December 2025

Study information

• Verified date: January 2023
• Source: St. Justine's Hospital
• Contact: Francine M Ducharme, MD
• Phone: 514-345-4931
• Email: francine.m.ducharme[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 865
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 5 Years

Eligibility

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 (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)

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

Related Conditions & MeSH terms

• Asthma

Intervention

Dietary Supplement:
• Vitamin D
2 mL of 50,000 IU/mL at baseline and at 3.5 months with a daily dose of 1 mL (400 IU/mL) for 7 months
• Placebo
2 mL of placebo at baseline and at 3.5 months with a daily dose of placebo (1 mL) for 7 months

Locations

Country	Name	City	State
Canada	Children's Hospital of London Health Sciences Centre	London	Ontario
Canada	CHU Sainte Justine	Montreal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
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

Sponsors (3)

Lead Sponsor	Collaborator
Professor Francine Ducharme	Canadian Institutes of Health Research (CIHR), EURO-PHARM International Canada, Inc.

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Jensen ME, Ducharme FM, Alos N, Mailhot G, Masse B, White JH, Sadatsafavi M, Khamessan A, Tse SM, Alizadehfar R, Bock DE, Daigneault P, Lemire C, Yang C, Radhakrishnan D. Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial. BMJ Open. 2019 Dec 30;9(12):e033075. doi: 10.1136/bmjopen-2019-033075. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hypercalciuria	Group difference in the proportion of children with =1 occurrence of hypercalciuria (urinary calcium: creatinine ratio >1.38 mmol/mmol for children aged 1-<2 years, or >1.1 mmol/mmol for children aged 2-<5 years, or >0.77 mmol/mmol for children aged =5 years)	7 months
Other	Hypercalcemia	Group difference in the proportion of children with clinically significant hypercalcemia (>2.63 mmol/L)	7 months
Other	Elevated serum 25-hydroxyvitamin D	Group difference in the proportion of children with =1 occurrence of elevated serum 25OHD (greater than 250 nmol/L)	7 months
Other	Adverse Health Events	Group difference in the distribution of adverse health events	7 months
Other	Gene expression	Group difference in the change in gene expression levels (between baseline and 3.5 months) in blood peripherical mononuclear cells, adjusted for cell distribution estimated from lymphocyte differentiation in a subset of patients	3.5 months
Primary	Number of asthma exacerbations per child treated with rescue oral corticosteroids	Group difference in the mean number of exacerbations treated with rescue oral corticosteroids/child	7 months
Secondary	Laboratory-confirmed respiratory infections	Group difference in mean number of laboratory-confirmed respiratory infections during asthma exacerbations	7 months
Secondary	Severity of asthma symptoms during asthma exacerbations	Group difference in the mean severity of asthma symptoms documented on the 'Asthma Flare-up Diary for Young Children'	7 months
Secondary	Duration of asthma symptoms during asthma exacerbations	Group difference in the mean duration of asthma symptoms documented on the validated 'Asthma Flare-up Diary for Young Children'	7 months
Secondary	Intensity of use of rescue ß2-agonists during asthma exacerbations	Group difference in the mean cumulative use of rescue ß2-agonists during exacerbations documented on the validated 'Asthma Flare-up Diary for Young Children'	7 months
Secondary	Parents' functional status during asthma exacerbations	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'	7 months
Secondary	Mean number of ED visits for asthma exacerbations	Group difference in mean number of ED visits for asthma exacerbations	7 months
Secondary	De-intensification of preventive asthma therapy	Group difference in proportion of children with de-intensification of preventive asthma therapy	7 months
Secondary	Intervention cost-effectiveness	Cost of intervention vs. cost (family expenses and health care) of exacerbations	7 months