DO IT Trial: Vitamin D Outcomes and Interventions In Toddlers (DO IT)

Vitamin D can be made in the skin by exposure to sunlight and can be found in certain foods. Vitamin D levels are alarmingly low in many North American children. Several health issues have been linked with low vitamin D. These include colds caused by viruses and asthma attacks. However, no study has determined whether vitamin D supplementation can reduce the risk of these conditions in young children where they are most common and most severe.

The goals of this study are to determine whether wintertime high dose vitamin D supplementation of preschoolers can prevent colds and asthma attacks. The investigators also aim to work out how much money would be saved by the health care system and society if preschoolers were routinely supplemented with Vitamin D during the winter. The investigators believe that preschoolers receiving 'high dose' vitamin D supplementation during the wintertime will be less likely to have colds, asthma attacks, and low vitamin D levels and will be less likely to use the medical system and keep their parents away from work.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Avitaminosis; Asthma
• Intervention / Treatment: Drug: Vitamin D3 - Cholecalciferol 2000 IU; Drug: Vitamin D - Cholecalciferol 400 IU

• Study Type: Interventional
• Enrollment (Actual): 703
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for sick children
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy children by parental report
2. Have reached their 1st birthday but not past their 6th birthday
3. Present to a TARGet Kids! practice for routine primary healthcare prior to viral season (September through November)
4. Parents provide informed consent to participate.

Exclusion Criteria:

1. Children with gestational age < 32 weeks
2. Children with chronic illness (except for asthma) on parental report which is known to interfere with vitamin D metabolism and increase the risk of respiratory infection
3. Children with a sibling participating in the study to reduce clustering effects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2000 IU per day vitamin D	Drug: Vitamin D3 - Cholecalciferol 2000 IU; One drop per day (liquid), 2000 IU, 4 to 9 months depending on date of enrollment and date of follow-up; Other Names: Ddrops 2000 IU
Active Comparator: 400 IU per day vitamin D	Drug: Vitamin D - Cholecalciferol 400 IU; One drop per day (liquid), 400 IU, 4 to 9 months depending on date of enrollment and date of follow-up; Other Names: Baby Ddrops; Health Canada NPN #80001869

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Laboratory confirmed upper respiratory tract infections	Parents of enrolled children will be asked to obtain a nasal swab from their child and complete a symptom checklist with each URTI. Reverse transcriptase polymerase chain reaction will be performed on each sample. Samples will be tested for 18 common respiratory viruses using the ID-TagTM RVP assay using the Luminex xMAPTM system.	Up to 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of parent reported upper respiratory tract infections	Parental reported URTI symptoms will be defined as two or more of fever, cough, runny nose, sore throat, headache, vomiting, feels unwell, muscle aches, ear ache or infection, poor appetite, not sleeping well, cranky/fussy, low energy or crying more than usual from a validated parent completed symptom checklist.	Up to 8 months
Number of Asthma exacerbations	Asthma exacerbation will be defined as a wheezing episode in children with asthma as obtained from parent completed symptom checklist based on the International Study of Asthma and Allergies in Childhood (ISAAC).	Up to 8 months
Serum vitamin D level	Blood for serum levels will be drawn by trained pediatric phlebotomists from for determination of 25-hydroxyvitamin D. Total 25-hydroxyvitamin D will be measured from serum samples using a competitive two-step chemiluminescence assay.	5-8months
Direct and indirect economic costs associated with upper respiratory tract infections	Cost-consequence and cost-effectiveness analyses will be conducted using data from this clinical trial. A societal perspective will be employed as both direct health service utilization costs as well as indirect costs to families from URTI will be calculated for the 400 IU per day versus 2000 IU per day groups.	16 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass index z-score	Weight and height will be measured at both study baseline and follow-up by trained research assistants. BMI will be determined by dividing the children's measured weight (kg) by height (m2). The BMI z-score [zBMI] will be determined using the World Health Organization Growth standards, standardized for age and sex.	Up to 8 months
Waist circumference z-score	Waist circumference will be measured at both study baseline and follow-up by trained research assistants. Waist circumference will be measured at the mid-axillary line above the right iliac crest. Waist circumference z-score will be calculated internally within the entire TARGet Kids! study cohort.	Up to 8 months
Serum Lipids	Blood for serum levels will be drawn by trained pediatric phlebotomists from for determination of total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and non-HDL cholesterol.	Up to 8 months

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Unity Health Toronto; Mount Sinai Hospital, Canada
• Investigators: Principal Investigator: Jonathon L Maguire, MD, MSc, St. Michael's Hospital, Toronto, Ontario, Canada

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.
• Aglipay M, Birken CS, Parkin PC, Loeb MB, Thorpe K, Chen Y, Laupacis A, Mamdani M, Macarthur C, Hoch JS, Mazzulli T, Maguire JL; TARGet Kids! Collaboration. Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children. JAMA. 2017 Jul 18;318(3):245-254. doi: 10.1001/jama.2017.8708.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimate): August 18, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin D; Asthma; Randomized Controlled Trial; Respiratory Tract Infections; Dietary Supplements; Child, Preschool
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Nutrition Disorders; Deficiency Diseases; Malnutrition; Respiratory Tract Infections; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 1000025147