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MAPS & ITEC Cohorts: 6-8 Years Follow-up

Phase 2
Completed
Conditions
Asthma
Immunotherapy
Allergy and Immunology
Interventions
Drug: Normal saline
Drug: House dust-mite SLIT
Registration Number
NCT03763630
Lead Sponsor
University of Southampton
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
263
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control armNormal salineNormal saline
Intervention armHouse dust-mite SLITHouse dust-mite SLIT
Primary Outcome Measures
NameTimeMethod
Clinical Asthma - parental questionnaireAge 6 years

Comparison of clinical asthma, as assessed by parental questionnaire, at age 6 years between control and intervention groups. Clinical asthma will be defined as either doctor diagnosed asthma or presence of wheeze and asthma medication use within the past year.

Clinical Asthma- spirometry with reversibility6 years

Comparison of clinical asthma, as assessed by lung function testing, at age 6 years between control and intervention groups. Clinical asthma will be defined as in improvement in FEV1 (Forced Expiratory Volume in 1 second) of 12% or more following administration of salbutamol inhaler (bronchodilator).

Secondary Outcome Measures
NameTimeMethod
Asthma comparisonAge 6 years

Comparison of asthma, as defined by wheeze plus bronchial hyperreactivity

Bronchial hyper-responsivenessAge 6 years

Comparison of bronchial hyperresponsiveness, as determined by methacholine bronchial allergen challenge, at age 6 years.

Cumulative sensitizationAge 6 years

Comparison of cumulative sensitization to one or more of 6 common allergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.

Cumulative aeroallergen sensitizationAge 6 years

Comparison of cumulative sensitization to one or more of 6 common aeroallergens, as assessed by skin prick test, up to 6-8 years of age between control and interventions groups.

Clinical atopic disease- parental questionnaireAge 6 years

Comparison of clinical allergic diseases/symptoms (atopic eczema, wheeze, allergic rhinitis, food allergy) at 18 months, 3 years and 6 years of age between control and intervention groups. Presence of clinical disease evaluated through parental questionnaires

Airway inflammation level- exhaled nitric oxide measurementAge 6 years

Comparison of airway inflammation level, as assessed by exhaled nitric oxide, between placebo and intervention group age 6 years

House dust-mite sensitizationAge 6 years

Comparison of sensitization to house dust mite, as assessed by skin prick test, at 18 months, 3 years and 6-8 years of age between control and intervention groups.

Trial Locations

Locations (2)

University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, Hampshire, United Kingdom

David Hyde Asthma and Allergy Centre

🇬🇧

Newport, Isle Of White, United Kingdom

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