Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03365687
Recruitment Status : Recruiting
First Posted : December 7, 2017
Last Update Posted : September 30, 2020
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
EURO-PHARM International Canada, Inc.
Information provided by (Responsible Party):
Professor Francine Ducharme, St. Justine's Hospital

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.

Condition or disease Intervention/treatment Phase
Asthma Dietary Supplement: Vitamin D Dietary Supplement: Placebo Phase 3

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 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 865 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation.
Masking: Triple (Participant, 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 obtain allocated treatment number, 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 (DIVA)
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


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
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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Laboratory-confirmed respiratory infections [ Time Frame: 7 months ]
    Group difference in mean number of laboratory-confirmed respiratory infections during asthma exacerbations

  2. 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'

  3. 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'

  4. 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'

  5. 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'

  6. Mean number of ED visits for asthma exacerbations [ Time Frame: 7 months ]
    Group difference in mean number of ED visits for asthma exacerbations

  7. De-intensification of preventive asthma therapy [ Time Frame: 7 months ]
    Group difference in proportion of children with de-intensification of preventive asthma therapy

  8. Intervention cost-effectiveness [ Time Frame: 7 months ]
    Cost of intervention vs. cost (family expenses and health care) of exacerbations


Other Outcome Measures:
  1. Hypercalciuria [ Time Frame: 7 months ]
    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)

  2. Hypercalcemia [ Time Frame: 7 months ]
    Group difference in the proportion of children with clinically significant hypercalcemia (>2.63 mmol/L)

  3. 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)

  4. Adverse Health Events [ Time Frame: 7 months ]
    Group difference in the distribution of adverse health events

  5. Gene expression [ Time Frame: 3.5 months ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Francine M Ducharme, MD 514-345-4931 ext 4398 francine.m.ducharme@umontreal.ca
Contact: Amina Hasanova, MSc 514-345-4931 ext 2157 amina.hasanova@recherche-ste-justine.qc.ca

Locations
Layout table for location information
Canada, British Columbia
British Columbia Children's Hospital 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 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 Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Dhenuka Radhakrishnan, MD    1-6137377600 ext 2868    dradhakrishnan@cheo.on.ca   
Principal Investigator: Dhenuka Radhakrishnan, MD         
Canada, Quebec
Montreal Children's Hospital Recruiting
Montreal, Quebec, Canada, H3H 1P3
Contact: Reza Alizadehfar, MD       reza.alizadehfar@muhc.mcgill.ca   
Contact: Duncan Lejtenyi, MSc    1-514-412-4400 ext 22369    duncan.lejtenyi@muhc.mcgill.ca   
Principal Investigator: Reza Alizadehfar, MD         
CHU Sainte Justine Recruiting
Montreal, Quebec, Canada, H3T1C5
Contact: Sze Man Tse    514-345-4931 ext 54    sze.man.tse@umontreal.ca   
Principal Investigator: Sze Man Tse         
Maisonneuve-Rosemont Hospital Recruiting
Montreal, Quebec, Canada
Contact: Marc-Andre Turcot, MD       marc-andre.turcot@umontreal.ca   
Principal Investigator: Marc-Andre Turcot         
CHU de Québec-Université Laval Recruiting
Québec, Quebec, Canada, G1V 4G2
Contact: Patrick Daigneault, MD       Patrick.Daigneault@mail.chuq.qc.ca   
Contact: Louise Gosselin    418-525-4444 ext 48290    louise.gosselin@chudequebec.ca   
Principal Investigator: Patrick Daigneault, MD         
CHU de Sherbrooke Active, not recruiting
Sherbrooke, Quebec, Canada, J1G 2E8
Sponsors and Collaborators
Professor Francine Ducharme
Canadian Institutes of Health Research (CIHR)
EURO-PHARM International Canada, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Francine M Ducharme, MD Study Principal Investigator
Publications:
Layout table for additonal information
Responsible Party: Professor Francine Ducharme, Pediatrician, St. Justine's Hospital
ClinicalTrials.gov Identifier: NCT03365687    
Other Study ID Numbers: MP-21-2018-1657
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Vitamin D
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents