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Vitamin D in Preschoolers With Viral-induced Asthma (DIVA)

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ClinicalTrials.gov Identifier: NCT02197702
Recruitment Status : Completed
First Posted : July 23, 2014
Last Update Posted : June 21, 2018
Sponsor:
Collaborators:
The Hospital for Sick Children
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Montreal Children's Hospital of the MUHC
British Columbia Children's Hospital
London Health Sciences Centre
Information provided by (Responsible Party):
Professor Francine Ducharme, St. Justine's Hospital

Brief Summary:
In this 7-month randomized controlled trial, children aged 1-6 years with 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. This study will test whether children receiving a high dose of vitamin D 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 2 Phase 3

Detailed Description:

IMPORTANT NOTE: Due to receiving a 2-year partial funding enabling only a single-centre pilot trial, rather than an adequately-powered multicentre study, the primary outcome was modified post hoc for the overall change from baseline in total serum 25OHD during the study as well as at 3.5 and 7 months, similar to our previous pilot study.(NCT01999907) Post hoc secondary outcomes included the group difference in the proportion of children with total 25OHD ≥75 nmol/L at 3.5 and 7 months and in the rate of oral corticosteroid courses per child. Other a priory specified outcomes included the proportion of children with hypercalciuria (Ca:Cr) >1.25 (1-2 years), >1 (2-5 years) nmol/nmol at any point in time; proportion of children with ≥1 exacerbation requiring rescue oral steroids (former primary outcome); number of emergency department (ED) visits; intensity and duration of asthma symptoms and cumulative use of rescue ß2-agonist use, documented on Asthma Flare-up Diary for Young Children (ADYC); the impact of parents' functional status during exacerbations ascertained on the Effect of a child's asthma flare-up on parents; and duration of URTI.

Based on this analysis of this new post-hoc primary outcome, we have changed the intervention and the primary outcome and obtained funding for a new large multicentre study NCT03365687. it is thus important to share the results of this current trial with other investigators

PRIOR REPORTED DESCRIPTION Design: A multicenter triple-blind randomized parallel-group, placebo-controlled trial of vitamin D3 supplementation. Children aged 1-5 years with (i) physician-diagnosed asthma, predominantly triggered by upper respiratory tract infections (URTIs), (ii) ≥4 reported URTIs in the past year, and (iii) ≥1 exacerbation requiring OCS (a recognised marker of moderate and severe exacerbations) in the past 6 months or ≥2 in the past 12 months, will be randomly allocated to one of two treatments in blocks of 4-6, stratified on recruitment site: Intervention group (n=432)-100,000 IU oral vitamin D3; control group (n=432)-identical placebo, for 2 oral doses, 3.5 months apart. Co-intervention with asthma therapy (preventive or pre-emptive ICS) will be left to the discretion of the physician and documented. Children will be followed every 3.5 months as per usual practice, with a home visit 10 days after each bolus, during which urine and blood will be sampled for urinary calcium:creatinine ratio, serum vitamin D, markers of calcium metabolism, and mechanistic exploration. A validated diary will serve to document the intensity and severity of exacerbations. In two sites, preschool lung function will be documented (if ≥ 3yrs). Outcomes: Primary endpoint-number of exacerbations requiring rescue oral corticosteroids (OCS) per child, documented by medical and pharmacy records. Secondary outcomes: duration and severity of exacerbations (symptoms & β2-agonist use, by diary; emergency visits, by medical records), parental functional status (by validated instrument), asthma therapy intensification and health care and direct costs (by health records & parent reports). Safety, mechanistic, exploratory outcomes: hypercalciuria, calcium metabolism, excess vitamin D, change in serum gene expression at 10 days (first 25 patients); and change from baseline at 7 months in preschool lung function (2 sites). Based on 3 published RCTs, a sample of 432 per arm (400+7.5% attrition) will provide 80% power (2-tailed alpha of 5%) to detect a 25% reduction in number of exacerbations requiring OCS/child (0.55 vs. 0.4125).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D In the Prevention of Viral-induced Asthma of Preschoolers: a Randomised Controlled Trial (RCT)- (DIVA)
Study Start Date : September 2014
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

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Arm Intervention/treatment
Placebo Comparator: Placebo
2 ml identical placebo taken by mouth at baseline and 3.5 months.
Dietary Supplement: placebo
Two doses of identical placebo (2 mL) given 3.5 months part, once in the fall, once in the winter

Active Comparator: Vitamin D
Vitamin D (100,000IU) given in a 2 ml oral dose at baseline and 3.5months.
Dietary Supplement: vitamin D
Two doses of cholecalciferol 100,000 unit (2 mL) given 3.5 months apart, once in the fall, once in the winter
Other Name: cholecalciferol




Primary Outcome Measures :
  1. Change from baseline in serum 25OHD [ Time Frame: During the 7-month follow-up period ]
    Group difference in the adjusted change from baseline 25OHD over time and specifically at 3.5 and 7 months


Secondary Outcome Measures :
  1. Proportion of children with total 25OHD ≥75 nmol/L [ Time Frame: at 3.5 and 7 months ]
    Group difference in the proportion of children with total 25OHD ≥75 nmol/L


Other Outcome Measures:
  1. Hypercalciuria [ Time Frame: At any point during the 7-month follow-up period ]
    Group difference in the proportion of children with ≥1 occurrence of hypercalciuria (urinary calcium: creatinine greater than 1.25mmol/mmol for children aged 1-2yrs (or greater than 1mmol/mmol for those aged 2-5yrs)

  2. Elevated serum 25-hydroxyvitamin D (25OHD) [ Time Frame: At any point during the 7-month follow-up period ]
    Proportion of children with ≥1 occurrence of elevated serum 25OHD (greater than 250nmol/L)

  3. Perturbation of the calcium homeostasis [ Time Frame: At any point during the 7-month follow-up period ]
    Proportion of children with ≥1 occurrence of a perturbation of the calcium homeostasis (serum Ca, Ph, Alkaline phosphatase), defined as outside normal laboratory values

  4. RNA expression [ Time Frame: Over the 7 months after the intial dose of Vit D/Placebo ]
    Group difference in the change from baseline in RNA expression measured between 0, 10 days, 3.5 months and 7 months post initial dose of Vit D/Placebo

  5. Duration of URTIs [ Time Frame: During an URTI during the 7-month follow-up period ]
    Group difference in the duration of URTI as documented by parents at the end of each episode

  6. Viral upper respiratory tract infections (URTI) [ Time Frame: During the 7-month follow-up period ]
    Group difference in the number of reported viral upper respiratory tract infections

  7. Emergency department visit for an asthma flare-up [ Time Frame: During the 7-month follow-up period ]
    Group difference in the number of emergency department visits for asthma

  8. Rescue β2-agonist use during an asthma flare-up [ Time Frame: During the 7-month follow-up period ]
    Group difference in the cumulative daily use of rescue β2-agonist use as documented by parents on the 'Asthma Flare-up Diary for Young CHildren' during a URTI or an asthma exacerbation

  9. Severity of asthma symptoms during an asthma flare-up [ Time Frame: During an URTI or flare-up during the 7-month follow-up period ]
    Group difference in the severity on the asthma symptoms documented as the sum of daily score on the 'Asthma FLare-up DIary for Young Children' questionnaire

  10. Duration of asthma symptoms during a flare-up [ Time Frame: During an URTI or flare-up during the 7-month follow-up period ]
    Group difference in the duration of asthma symptoms documented on the 'Asthma FLare-up DIary for Young Children' questionnaire

  11. Exacerbations requiring rescue oral corticosteroids [ Time Frame: During the 7-month follow-up period ]
    Mean group rate of exacerbations requiring rescue oral corticosteroids/child

  12. Patients with exacerbations requiring rescue oral corticosteroids [ Time Frame: During the 7-month follow-up period ]
    Proportion of children with ≥1 exacerbation requiring rescue oral corticosteroids

  13. Impact of exacerbations on caregivers' functional status [ Time Frame: During an URTI or flare-up during the 7-month follow-up period ]
    Group difference in the caregivers' functional status measured on the 'Effect of a child's asthma flare-up on parents' questionnaire

  14. Impact of exacerbations on caregivers' workday lost [ Time Frame: During an URTI or flare-up during the 7-month follow-up period ]
    Group difference in the caregivers' number of workday lost



Information from the National Library of Medicine

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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 Global Initiative for Asthma (GINA) guidelines
  • URTIs as the main asthma trigger (parental report)
  • ≥4 URTIs in the past 12 months (parental report)
  • ≥1 asthma exacerbation requiring rescue oral corticosteroids (OCS) in the past 6 months or ≥2 in the past 12 months

Exclusion Criteria:

  • intake or intention to use more than 400 IU/day of vitamin D supplement
  • extreme prematurity (<28 weeks gestation)
  • infants <12 months of age
  • no vitamin D supplementation when breast-fed
  • recent (<1 year) immigrants from a region at high risk of rickets
  • children with vitamin D restrictive diets e.g. vegans
  • other chronic respiratory disease (broncho-pulmonary dysplasia; cystic fibrosis)
  • condition(s) that alter calcium or vitamin D metabolism/absorption (hypo/hyperparathyroidism, kidney/liver disease, inflammatory bowel disease)
  • medications that interfere with vitamin D metabolism (anti-epileptics, diuretics, antacids, anti-fungal drug)
  • vitamin D supplementation >1000 IU/ day in last 3 months
  • anticipated difficult follow-up (unable to attend clinic visits; plan to leave the province).

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): NCT02197702


Locations
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Canada, Quebec
CHU Sainte Justine
Montreal, Quebec, Canada, H3T1C5
Sponsors and Collaborators
St. Justine's Hospital
The Hospital for Sick Children
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Montreal Children's Hospital of the MUHC
British Columbia Children's Hospital
London Health Sciences Centre
Investigators
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Principal Investigator: Francine M Ducharme, MD St. Justine's Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Professor Francine Ducharme, Principal Investigator, St. Justine's Hospital
ClinicalTrials.gov Identifier: NCT02197702    
Other Study ID Numbers: DIVA
First Posted: July 23, 2014    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Professor Francine Ducharme, St. Justine's Hospital:
RCT
asthma
pediatric
virus
corticosteroid
Additional relevant MeSH terms:
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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