Clinical trial NCT02112734: Can Vitamin D Supplementation in the First Year of Life Prevent Food Allergy in Infants? the VITALITY Trial: Parts 1&2
Official title: Can Vitamin D Supplementation Prevent Food Allergy in Infants? the VITALITY Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Food Allergy
Keywords: vitamin D
food allergy
eczema
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2014-04-14
Enrollment: 2739
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: We report that Australia has the highest prevalence of Immunoglobulin(Ig)E-mediated food allergy in the world, with 10% of infants having challenge-proven food allergy in Melbourne. There has been a 5-fold increase in hospital admissions for life-threatening anaphylaxis. These changes are most pronounced in children less than 5 years, suggesting a causal role for early life determinants. We have primary data to inform hypotheses for the rise in food allergy, which appears to result from potentially modifiable factors related to the modern lifestyle, particularly Vitamin D insufficiency (VDI). We propose an intervention study to assess if infant Vitamin D supplementation during the first year of life significantly decreases the risk of early-onset food allergy and other allergic disease at 12 months (part 1) and 6 years of age (part 2). Australia is ideally placed to answer this important question since, unlike the USA, Canada and Europe, there are no population recommendations for routine infant supplementation with Vitamin D and we are one of the few developed countries that do not supplement the food chain supply with Vitamin D.

Detailed description: There is an urgent need to prevent the onset and progression of food allergy in our population. Evidence demonstrates that food allergy and atopic eczema represent the earliest manifestations of the atopic march with 50% of infants with food allergy predicted to develop respiratory allergic diseases later in life. We report that Australia has the highest prevalence of Immunoglobulin(Ig)E-mediated food allergy in the world, with 10% of infants having challenge-proven food allergy in Melbourne. There has been a 5-fold increase in hospital admissions for life-threatening anaphylaxis. These changes are most pronounced in children less than 5 years, suggesting a causal role for early life determinants. We have primary data to inform hypotheses for the rise in food allergy, which appears to result from potentially modifiable factors related to the modern lifestyle, particularly Vitamin D insufficiency (VDI), and have demonstrated an association between VDI and increased risk of challenge-proven food allergy in 12-month old infants, which supports numerous ecological studies showing an increased risk of food allergy the further a child resides from the equator (associated with decreased UV exposure and Vitamin D levels). Despite Australia's sunny climate, population rates of VDI have steadily increased in infants and pregnant women in parallel to the apparent rise in food allergic disease. This association is biologically plausible, as there is evidence Vitamin D is critical to the healthy development of the immune system in early life. We propose an intervention study to assess if infant Vitamin D supplementation during the first year of life significantly decreases the risk of early-onset food allergy and other allergic disease at 12 months (part 1) and 6 years of age (part 2). Australia is ideally placed to answer this important question since, unlike the USA, Canada and Europe, there are no population recommendations for routine infant supplementation with Vitamin D and we are one of the few developed countries that do not supplement the food chain supply with Vitamin D.

Eligibility criteria: Inclusion Criteria:

Each participant must meet the following criteria to be included in this study:

* Healthy, term (born no earlier than 2 weeks before estimated date of delivery), predominantly breastfeeding infants aged 6 to 12 weeks (inclusive) who are expected to be predominantly breastfed for at least 6-months. This will be determined by answering yes/no to question 'do you intend/wish to breastfeed until your infant is at least 6 months of age.' Up to one bottle (approx. 120mL) of formula per 24 hours at the time of screening is acceptable, as this will contain \<100 IU vitamin D.
* Has a parent/legally acceptable representative (LAR) capable of understanding the informed consent document and providing consent on the subject's behalf,
* The parent must expect to be able to complete 4 online questionnaires over the infant's first 12 months of life and for the infant to be available for skin prick testing (+/- food challenge) at The Royal Children's Hospital at 12 months of age.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

* Infants who are currently receiving vitamin D supplementation
* Infants on medication that interferes with vitamin D metabolism
* Poor health due to a current or past significant disease state or congenital abnormality.
* Prematurity \<37 weeks/low birth weight \<2500 g/Small for gestational age (SGA)
* Unable to provide consent without the aid of an interpreter.
* Women at high risk of vitamin D deficiency with infants on vitamin D supplementation.

Primary outcomes:
measure: The prevalence of challenge-proven food allergy at 12 months of age
timeFrame: At 12 months of age
measure: The occurrence of definite food allergy or tolerance at 6 years of age
timeFrame: At 6 years of age
Secondary outcomes:
measure: The prevalence of food sensitisation at 12 months of age determined by SPT positive
timeFrame: At 12 months of age
measure: The prevalence of doctor diagnosed eczema during the first postnatal year
timeFrame: During the first postnatal year
measure: The prevalence of vitamin D insufficiency (serum concentration of 25(OH)D <50 nmol/L ) at age 12 months determined by measuring blood taken at the 12 month clinic visit
timeFrame: At 12 months of age
measure: Allergy-related healthcare utilisation within the first 12 months of life
timeFrame: Within the first 12 months of life
measure: Infection episodes within the first 12 months of life
timeFrame: Within the first 12 months of life
measure: Measure of height at 12 months of age
timeFrame: At 12 months of age
measure: Measure of weight at 12months of age
timeFrame: At 12 months of age
measure: Wheeze episodes within the first 12 months of life
timeFrame: Within the first 12 months of life
measure: The occurrence of food sensitisation at 6 years of age determined by SPT positive
timeFrame: At 6 years of age
measure: The occurrence of asthma in the first 6 years of life
timeFrame: At 6 years of age
measure: The occurrence of eczema in the first 6 years of life
timeFrame: Within first 6 years of life
measure: The prevalence of vitamin D insufficiency (serum concentration of 25(OH)D <50 nmol/L ) at age 6 years determined by measuring blood taken at the 6 year clinic visit
timeFrame: At 6 years of age
measure: Allergy-related healthcare utilisation in the first 6 years of life
timeFrame: Within first 6 years of life
measure: Measure of height at 6 years of age
timeFrame: At 6 years of age
measure: Measure of Waist circumference at 6 years of age
timeFrame: At 6 years of age
measure: Measure of Hip circumference at 6 years of age
timeFrame: At 6 years of age
measure: Lung function at 6 years of age
timeFrame: At 6 years of age
measure: The occurrence of rhinitis in the first 6 years of life
timeFrame: Within first 6 years of life
measure: Psychosocial Distress at 6 years of age
timeFrame: At 6 years of age
measure: Psychosocial health at 6 years of age
timeFrame: At 6 years of age
measure: Quality of life at 6 years of age
timeFrame: At 6 years of age
measure: Quality of life regarding Food Allergy at 6 years of age
timeFrame: At 6 years of age
measure: Cardiovascular health (vascular function) at 6 years of age
timeFrame: At 6 years of age
measure: Cardiovascular health (Carotid and aortic Intima-Media Thickness) at 6 years of age
timeFrame: At 6 years of age
measure: Cardiovascular health (Blood pressure) at 6 years of age
timeFrame: At 6 years of age
measure: Cardiovascular health (Arterial stiffness) at 6 years of age
timeFrame: At 6 years of age
measure: Dental health at 6 years of age
timeFrame: At 6 years of age
measure: Hearing health at 6 years of age
timeFrame: At 6 years of age
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Murdoch Childrens Research Institute
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Kirsten Perrett, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Allen KJ, Koplin JJ, Ponsonby AL, Gurrin LC, Wake M, Vuillermin P, Martin P, Matheson M, Lowe A, Robinson M, Tey D, Osborne NJ, Dang T, Tina Tan HT, Thiele L, Anderson D, Czech H, Sanjeevan J, Zurzolo G, Dwyer T, Tang ML, Hill D, Dharmage SC. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol. 2013 Apr;131(4):1109-16, 1116.e1-6. doi: 10.1016/j.jaci.2013.01.017. Epub 2013 Feb 27.
citation: Allen KJ, Panjari M, Koplin JJ, Ponsonby AL, Vuillermin P, Gurrin LC, Greaves R, Carvalho N, Dalziel K, Tang ML, Lee KJ, Wake M, Curtis N, Dharmage SC. VITALITY trial: protocol for a randomised controlled trial to establish the role of postnatal vitamin D supplementation in infant immune health. BMJ Open. 2015 Dec 16;5(12):e009377. doi: 10.1136/bmjopen-2015-009377.