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

NCT ID: NCT03365687

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 323 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2024-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo orally at baseline and at 3.5 months with daily placebo during 7 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

2 mL of placebo at baseline and at 3.5 months with a daily dose of placebo (1 mL) for 7 months

Interventions

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

2 mL of placebo at baseline and at 3.5 months with a daily dose of placebo (1 mL) for 7 months

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Cholecalciferol

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

EURO-PHARM International Canada, Inc.

OTHER

Sponsor Role: collaborator

Professor Francine Ducharme

OTHER

Sponsor Role: lead

Responsible Party

Professor Francine Ducharme

Pediatrician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Francine M Ducharme, MD

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator

Locations

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

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 31892662 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MP-21-2018-1657

Identifier Type: -

Identifier Source: org_study_id