Vitamin D in Preschoolers With Viral-induced Asthma

Asthma Clinical Trial

— DIVA  

Official title:

Vitamin D In the Prevention of Viral-induced Asthma of Preschoolers: a Randomised Controlled Trial (RCT)- (DIVA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197702
• Other study ID #: DIVA
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 2014
• Est. completion date: July 2016

Study information

• Verified date: November 2016
• Source: St. Justine's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 5 Years

Eligibility

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).

Related Conditions & MeSH terms

• Asthma

Intervention

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
• placebo
Two doses of identical placebo (2 mL) given 3.5 months part, once in the fall, once in the winter

Locations

Country	Name	City	State
Canada	CHU Sainte Justine	Montreal	Quebec

Sponsors (6)

Lead Sponsor	Collaborator
St. Justine's Hospital	British Columbia Children's Hospital, Centre de recherche du Centre hospitalier universitaire de Sherbrooke, London Health Sciences Centre, Montreal Children's Hospital of the MUHC, The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hypercalciuria	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)	At any point during the 7-month follow-up period
Other	Elevated serum 25-hydroxyvitamin D (25OHD)	Proportion of children with =1 occurrence of elevated serum 25OHD (greater than 250nmol/L)	At any point during the 7-month follow-up period
Other	Perturbation of the calcium homeostasis	Proportion of children with =1 occurrence of a perturbation of the calcium homeostasis (serum Ca, Ph, Alkaline phosphatase), defined as outside normal laboratory values	At any point during the 7-month follow-up period
Other	RNA expression	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	Over the 7 months after the intial dose of Vit D/Placebo
Other	Duration of URTIs	Group difference in the duration of URTI as documented by parents at the end of each episode	During an URTI during the 7-month follow-up period
Other	Viral upper respiratory tract infections (URTI)	Group difference in the number of reported viral upper respiratory tract infections	During the 7-month follow-up period
Other	Emergency department visit for an asthma flare-up	Group difference in the number of emergency department visits for asthma	During the 7-month follow-up period
Other	Rescue ß2-agonist use during an asthma flare-up	Group difference in the cumulative daily use of rescue ß2-agonist use as documented by parents on the 'Asthma Flare-up Diary for Young CHildren' during a URTI or an asthma exacerbation	During the 7-month follow-up period
Other	Severity of asthma symptoms during an asthma flare-up	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	During an URTI or flare-up during the 7-month follow-up period
Other	Duration of asthma symptoms during a flare-up	Group difference in the duration of asthma symptoms documented on the 'Asthma FLare-up DIary for Young Children' questionnaire	During an URTI or flare-up during the 7-month follow-up period
Other	Exacerbations requiring rescue oral corticosteroids	Mean group rate of exacerbations requiring rescue oral corticosteroids/child	During the 7-month follow-up period
Other	Patients with exacerbations requiring rescue oral corticosteroids	Proportion of children with =1 exacerbation requiring rescue oral corticosteroids	During the 7-month follow-up period
Other	Impact of exacerbations on caregivers' functional status	Group difference in the caregivers' functional status measured on the 'Effect of a child's asthma flare-up on parents' questionnaire	During an URTI or flare-up during the 7-month follow-up period
Other	Impact of exacerbations on caregivers' workday lost	Group difference in the caregivers' number of workday lost	During an URTI or flare-up during the 7-month follow-up period
Primary	Change from baseline in serum 25OHD	Group difference in the adjusted change from baseline 25OHD over time and specifically at 3.5 and 7 months	During the 7-month follow-up period
Secondary	Proportion of children with total 25OHD =75 nmol/L	Group difference in the proportion of children with total 25OHD =75 nmol/L	at 3.5 and 7 months