Vitamin D to Reduce Colds and Asthma Attacks in Young Children (DIVA-pilot)

Vitamin D vs. Placebo in the Prevention of Viral-induced Exacerbations in Preschoolers With Asthma: a Pilot RCT

Viral infections are the main cause of asthma attacks in preschoolers, an age group with the highest rate of emergency visits due to asthma. While high doses of inhaled or oral corticosteroids provide benefits, these have been associated with adverse outcomes. Most asthmatic children have lower blood levels of vitamin D compared to non-asthmatic children. Low vitamin D level has been linked to more frequent and more severe asthma attacks as well as with higher dose requirement of inhaled corticosteroid. Recent studies show that vitamin D supplements can reduce the number of asthma attacks triggered by viral infections in children. Unfortunately, most people forget to take vitamin D every day during the fall and winter season as recommended in Canada. A solution is to give a vitamin D bolus by mouth. This has been shown to safely and effectively increase vitamin D levels in children. The investigators hypothesise that a vitamin D bolus given in clinic will sufficiently increase the blood level of vitamin D to prevent the expected winter decline in vitamin D, compared with placebo in preschool-aged children with asthma. This six-month pilot randomized controlled trial aims to: (1) show that a vitamin D bolus is superior to placebo in raising vitamin D levels; (2) record the number of asthma attacks and viral infections in enrolled participants; and (3) identify problems that may call for protocol changes.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Dietary supplement: daily vitamin D supplement; Other: Placebo; Dietary supplement: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children aged 1-5 years
• physician-diagnosed asthma as per GINA guidelines
• upper respiratory tract infections as the main asthma exacerbation trigger
• ≥4 respiratory infections in the past 12 months
• ≥1 exacerbation requiring rescue oral steroids in the past 6 months or ≥2 in the previous 12 months.

Exclusion Criteria:

• extreme prematurity (<28 weeks gestation)
• infants <12 months of age
• breastfed infants with no vitamin D supplementation
• recent (<1 year) immigrants from countries where rickets and malnutrition prevalent
• other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis)
• endocrine disorder of calcium/ vitamin D metabolism
• disorder/ disease with associated malabsorption (inflammatory bowel disease)
• kidney/ liver disease
• sickle cell anemia
• medications known to interfere with bone metabolism/ vitamin D levels
• vitamin D supplementation >1000 IU/ day in past 3 months
• unable to attend medical visit in 3-4 months
• plan to leave the province during the next 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; bolus placebo given in a 2ml dose by mouth at baseline. This group receives daily vitamin D supplement by mouth for the 6 month study (400IU cholecalciferol per day).	Dietary supplement: daily vitamin D supplement; Each group receives a daily vitamin D supplement for 6 months, providing 400IU per day.; Other Names: cholecalciferol (Pediavit); Other: Placebo; placebo given in a 2ml dose by mouth at baseline.
Active Comparator: Vitamin D; Vitamin D (100,000IU) bolus in a 2ml dose by mouth given at baseline. This group receives a daily vitamin D supplement by mouth for 6 months (400IU cholecalciferol per day).	Dietary supplement: daily vitamin D supplement; Each group receives a daily vitamin D supplement for 6 months, providing 400IU per day.; Other Names: cholecalciferol (Pediavit); Dietary supplement: Vitamin D; 100,000IU cholecalciferol given in a 2ml dose by mouth at baseline.; Other Names: cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum Vitamin D	mean change in serum vitamin D from baseline to 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adequate serum vitamin D	difference in the proportion of children with serum vitamin D ≥75nmol/L at 3 months	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
exacerbations requiring oral corticosteroids	number of patients with one or more exacerbations requiring oral steroids, as documented by pharmacy dispensation records and medical records	6 months
number of viral infections	number of patients/person-month of observation documented two days; parent-reported on the Canadian Acute Respiratory Illness and Flu Scale and; Positive viral presence, determined by polymerase chain reaction on nasal sample	6 months
Hypercalciuria	urinary calcium: creatinine ratio >1.25 (1-2 years) and >1 (2-5 years) mmol/mmol	any point during the 6 months
Cytokine/ chemokine profile	change in serum cytokine/ chemokine profile from baseline to 10 days post-bolus dose	10 days
duration of viral infections	number of days with respiratory tract symptoms as reported on the parent completed Canadian Acute Respiratory Illness & Flu Scale	in the event of a cold during the 6 months
severity of exacerbations	area under the curve for β-agonist use as documented by parent of the 'Asthma Flare-Up Diary for Young Children';; need for hospital admission	in the event of an exacberbation during the 6 months
duration of exacerbations	Number of days with asthma symptoms as reported on the parent-reported 'Asthma Flare-Up Diary for Young Children'	in the event of an exacerbation during the 6 months
participant retention	percentage of patients retained until 6 months after randomization	6 months
protocol adherence	participant attendance to all 4 home and clinic visits; percentage of patients with all 4 blood and urine tests collected; percentage of analyzable viral nasal swabs returned.	6 months

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Investigators: Principal Investigator: Francine M Ducharme, St. Justine's Hospital

Publications and helpful links

General Publications

• 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.
• Jensen ME, Mailhot G, Alos N, Rousseau E, White JH, Khamessan A, Ducharme FM. Vitamin D intervention in preschoolers with viral-induced asthma (DIVA): a pilot randomised controlled trial. Trials. 2016 Jul 26;17(1):353. doi: 10.1186/s13063-016-1483-1.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (Estimate): December 3, 2013

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: January 8, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: pediatric; asthma; RCT; steroid; virus diseases
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: VD0001; 12140 (Other Grant/Funding Number: Thrasher Research Fund)