Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers (DIVA)
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ClinicalTrials.gov Identifier: NCT03365687 |
Recruitment Status
:
Not yet recruiting
First Posted
: December 7, 2017
Last Update Posted
: December 7, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Asthma | Dietary Supplement: Vitamin D Dietary Supplement: Placebo | Phase 3 |
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 November 30, 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 7 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, de-intensification of preventive asthma therapy, cost effectiveness, and safety profile. A sample of 432 per arm (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 number of exacerbations requiring OCS per child.
An intention-to-treat (ITT) analysis will be carried out with all randomised children.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 865 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | This is a randomised, quadruble-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation. |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | The manufacturer, Europharm, will provide the active vitamin D3 and placebo preparations, identical in appearance and taste, in coded latex-free bottles. A web-based randomisation system will allow Site pharmacies to login, obtain allocated treatment, prepare the 2 mL bolus in coded syringes and the coded bottles containing the daily dose, and dispense study drugs in masked kits. |
Primary Purpose: | Prevention |
Official Title: | Vitamin D In the Prevention of Viral-induced Asthma in Preschoolers: a Randomized Controlled Multicenter Trial |
Estimated Study Start Date : | September 2018 |
Estimated Primary Completion Date : | May 2022 |
Estimated Study Completion Date : | December 2022 |

Arm | Intervention/treatment |
---|---|
Active Comparator: 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
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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
Other Name: Cholecalciferol
|
Placebo Comparator: Placebo
Placebo orally at baseline and at 3.5 months with daily placebo during 7 months
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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
|
- Number of asthma exacerbations per child treated with rescue oral corticosteroids [ Time Frame: 7 months ]Group difference in the mean number of exacerbations treated with rescue oral corticosteroids/child
- Laboratory-confirmed respiratory infections [ Time Frame: 7 months ]Group difference in mean number of laboratory-confirmed respiratory infections during asthma exacerbations
- Severity of asthma symptoms during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean severity of asthma symptoms documented on the 'Asthma Flare-up Diary for Young Children'
- Duration of asthma symptoms during asthma exacerbations [ Time Frame: 7 months ]Group difference in the mean duration of asthma symptoms documented on the validated 'Asthma Flare-up Diary for Young Children'
- Intensity of use of rescue β2-agonists during asthma exacerbations [ Time Frame: 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 [ Time Frame: 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'
- Mean number of ED visits for asthma exacerbations [ Time Frame: 7 months ]Group difference in number of ED visits for asthma exacerbations
- De-intensification of preventive asthma therapy [ Time Frame: 7 months ]Group difference in proportion of children with de-intensification of preventive asthma therapy
- Intervention cost-effectiveness [ Time Frame: 7 months ]Cost of intervention vs. cost (family expenses and health care) of exacerbations
- Hypercalciuria [ Time Frame: 7 months ]Group difference in the proportion of children with ≥1 occurrence of hypercalciuria (urinary calcium: creatinine greater than 1.25 mmol/mmol for children aged 1-2 yrs, or greater than 1 mmol/mmol for those aged 2-5 yrs)
- Hypercalcemia [ Time Frame: 7 months ]Group difference in the proportion of children with ≥1 occurrence of hypercalcemia
- Elevated serum 25-hydroxyvitamin D [ Time Frame: 7 months ]Group difference in the proportion of children with ≥1 occurrence of elevated serum 25OHD (greater than 250 nmol/L)
- Adverse Health Events [ Time Frame: 7 months ]Group difference in the distribution of adverse health events
- Gene expression [ Time Frame: 3.5 months ]Group difference in the change in gene expression between baseline and 3.5 months
- Serum and nasal metabolome [ Time Frame: 7 months ]Group difference in the change in serum and nasal metabolome over 7 months
- Distribution of laboratory-confirmed respiratory infections [ Time Frame: 7 months ]Group difference in the distribution of laboratory-confirmed respiratory infections
- Lung function [ Time Frame: 7 months ]Group difference in the change from baseline in lung function measured by respiratory resistance or lung clearance index at 7 months
- Bone remodelling [ Time Frame: 3.5 months ]Group difference in the change in markers of bone remodelling
- Severity of respiratory infection [ Time Frame: 7 months ]Group difference in the severity of respiratory infection ascertained on the adapted 'Respiratory Symptoms Questionnaire'

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Ages Eligible for Study: | 1 Year to 5 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 (pharmacy/medical records)
- ≥4 URTIs in the past 12 months (parental report)
- URTIs as the main asthma trigger (parental report)
Exclusion Criteria:
- Intake or intention to use > 400 IU/day of vitamin D3 supplements
- Extreme prematurity (< 28 week gestation)
- No vitamin D supplementation when breast-fed
- Vitamin D restrictive diets, that is, minimal milk intake
- Recent immigrants from regions at high risk of rickets
- Recent refugees
- Undernourished children
- Other chronic respiratory disease
- Condition(s) or drug(s) that alter calcium or vitamin D absorption or metabolism
- Anticipated difficulty with follow-up

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365687
Contact: Francine M Ducharme, MD | 514-345-4931 ext 4398 | francine.m.ducharme@umontreal.ca | |
Contact: Ilona Shemyakina, BSc | 514-345-4931 Ext. 7243 ext 4053 | ilona.shemyakina@umontreal.ca |
Canada, Alberta | |
Alberta Children's Hospital | Not yet recruiting |
Calgary, Alberta, Canada, T3B 6A9 | |
Contact: Mary Noseworthy, MD mary.noseworthy@ahs.ca | |
Principal Investigator: Mary Noseworthy, MD | |
Stollery Children's Hospital | Not yet recruiting |
Edmonton, Alberta, Canada, T6G 2B7 | |
Contact: Piushkumar Mandhane, MD mandhane@ualberta.ca | |
Principal Investigator: Piushkumar Mandhane, MD | |
Canada, British Columbia | |
British Columbia Children's Hospital | Not yet recruiting |
Vancouver, British Columbia, Canada, V6H 3V4 | |
Contact: Connie Yang, MD 1-6048752000 ext 4931 connie.yang@cw.bc.ca | |
Principal Investigator: Connie Yang, MD | |
Canada, Ontario | |
Children's Hospital of London Health Sciences Centre | Not yet recruiting |
London, Ontario, Canada, N6A 2V5 | |
Contact: Dirk Bock, MD 1-5196858824 Dirk.Bock@lhsc.on.ca | |
Principal Investigator: Dirk Bock, MD | |
Children's Hospital of Eastern Ontario | Not yet recruiting |
Ottawa, Ontario, Canada, K1H 8L1 | |
Contact: Dhenuka Radhakrishnan, MD 1-6137377600 ext 2868 dradhakrishnan@cheo.on.ca | |
Principal Investigator: Dhenuka Radhakrishnan, MD | |
Hospital for Sick Children | Not yet recruiting |
Toronto, Ontario, Canada, M5G 1X8 | |
Contact: Padmaja Subbarao, MD padmaja.subbarao@sickkids.ca | |
Principal Investigator: Padmaja Subbarao, MD | |
Canada, Quebec | |
Montreal Children's Hospital (MCH) | Not yet recruiting |
Montreal, Quebec, Canada, H3H 1P3 | |
Contact: Duncan Lejtenyi, MSc 1-5144124400 ext 22369 duncan.lejtenyi@muhc.mcgill.ca | |
Principal Investigator: Reza Alizadehfar, MD | |
CHU Sainte Justine | |
Montreal, Quebec, Canada, H3T1C5 | |
CHU de Québec-Université Laval | Not yet recruiting |
Québec, Quebec, Canada, G1V 4G2 | |
Contact: Patrick Daigneault, MD patrick.daigneault@mail.chuq.qc.ca | |
Principal Investigator: Patrick Daigneault, MD | |
CHU de Sherbrooke | Not yet recruiting |
Sherbrooke, Quebec, Canada, J1G 2E8 | |
Contact: Chantal Lemire, MD Chantal.Lemire@USherbrooke.ca | |
Principal Investigator: Chantal Lemire, MD |
Principal Investigator: | Francine M Ducharme, MD | Study Principal Investigator |
Responsible Party: | Professor Francine Ducharme, Pediatrician, St. Justine's Hospital |
ClinicalTrials.gov Identifier: | NCT03365687 History of Changes |
Other Study ID Numbers: |
MP-21-2018-1657 |
First Posted: | December 7, 2017 Key Record Dates |
Last Update Posted: | December 7, 2017 |
Last Verified: | December 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No | |
Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Professor Francine Ducharme, St. Justine's Hospital:
Children Vitamin D Respiratory viral infection Randomized controlled trial Asthma exacerbations |
Additional relevant MeSH terms:
Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |
Vitamins Vitamin D Ergocalciferols Cholecalciferol Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents |