Clinical trial NCT03763630: MAPS & ITEC Cohorts: 6-8 Years Follow-up
Official title: Primary Prevention of Atopy and Asthma With House Dust Mite Sublingual Immunotherapy: 6-8 Years Follow up
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunotherapy
Allergy and Immunology
Asthma
Keywords: Atopy
Early childhood
House Dust-mite
Sublingual immunotherapy
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: Isle of Wight NHS Trust
First posted: 2018-12-04
Enrollment: 263
Sex: ALL
Minimum age (years): 5
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study represents the follow-up, age 6-8 years, of children recruited at birth into two cohorts. The first cohort, the Mite Allergen Prevention Study (MAPS) was a double-blind, randomized controlled trial of the use of house dust-mite immunotherapy in the primary prevention of atopy and asthma. The Immune Tolerance in Early Childhood (ITEC) cohort is a separate observational cohort following up infants at high risk of atopy and correlating atopic disease development with epigenetic markers.

Detailed description: There is an epidemic of allergic disease in childhood and current preventative strategies have failed to demonstrate effectiveness outside of isolated trials. In a previous study, the efficacy of sublingual immunotherapy (SLIT) with house dust mite in preventing the development of allergic sensitisation in infants was assessed. The long term objective was to assess the effect of the intervention on the subsequent development of asthma. The hypothesis is that high dose oral immunotherapy will induce immune tolerance and reduce development of allergic sensitisation and later clinical asthma and allergy. A total of 111 infants at high risk of allergy (with ≥2 first degree relatives affected by asthma or allergy) but with no evidence of allergic sensitisation at recruitment were recruited. These infants were randomised at 6 months of age to receive a year of active HDM (House dust-mite) allergen extract delivered as SLIT or placebo intervention. At 18 months of age, there was a significant reduction in cumulative allergic sensitisation in the SLIT intervention group and a trend for reduction in allergic symptoms. They have also been followed up at 3 years of age. The data currently being analysed.

Additionally, an observational cohort (Immune Tolerance in Early Childhood, ITEC) was recruited at birth with the same inclusion criteria as the interventional one and assessed in the same way up to 3 years. This cohort has provided additional control data and samples to utilise in the analyses.

This proposed study is the 6-8 year follow up of these interventional and observational cohorts. The aim of the 6-8 year assessment is to assess the efficacy of prophylactic oral immunotherapy with HDM allergen in preventing the later development of asthma. The hypothesis is that high dose oral immunotherapy will induce immune tolerance and reduce development of allergic sensitisation and later clinical asthma and allergy. Participants will be assessed 6-8 years after finishing the intervention. The assessment will include a questionnaire, skin prick testing to the common aeroallergens and food allergens and lung function. Families and study investigators will both be blinded to participants' original treatment allocations. An additional aim is to investigate the epigenetic and immune mechanisms involved in the development of asthma and allergy and how allergen immunotherapy influence this process.

Eligibility criteria: Inclusion Criteria:

•Inclusion in original study cohorts at birth

•≥2 first-degree relatives with allergic disease (food allergy, asthma, eczema, rhinoconjunctivitis)

Exclusion Criteria:

* Not included in the original study cohorts
* Skin-prick test positive to any allergen (HDM, cat, grass pollen, peanut, egg and milk) age 5 months

Primary outcomes:
measure: Clinical Asthma - parental questionnaire
timeFrame: Age 6 years
measure: Clinical Asthma- spirometry with reversibility
timeFrame: 6 years
Secondary outcomes:
measure: Bronchial hyper-responsiveness
timeFrame: Age 6 years
measure: Asthma comparison
timeFrame: Age 6 years
measure: Airway inflammation level- exhaled nitric oxide measurement
timeFrame: Age 6 years
measure: Cumulative sensitization
timeFrame: Age 6 years
measure: Cumulative aeroallergen sensitization
timeFrame: Age 6 years
measure: House dust-mite sensitization
timeFrame: Age 6 years
measure: Clinical atopic disease- parental questionnaire
timeFrame: Age 6 years
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Newport
country: United Kingdom
facility: David Hyde Asthma and Allergy Centre
state: Isle Of White
Study officials:
affiliation: University of Southampton
name: Graham Roberts, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zolkipli Z, Roberts G, Cornelius V, Clayton B, Pearson S, Michaelis L, Djukanovic R, Kurukulaaratchy R, Arshad SH. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. J Allergy Clin Immunol. 2015 Dec;136(6):1541-1547.e11. doi: 10.1016/j.jaci.2015.04.045. Epub 2015 Jun 12.