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Clinical Trials/NCT03763630
NCT03763630CompletedPhase 2

Primary Prevention of Atopy and Asthma With House Dust Mite Sublingual Immunotherapy: 6-8 Years Follow up

University of Southampton2 sites in 1 country263 target enrollmentStarted: September 15, 2017Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Completed
Enrollment
263
Locations
2
Primary Endpoint
Clinical Asthma - parental questionnaire

Study Overview

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.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages
5 Months to 9 Months (Child)
Sex
All
Accepts Healthy Volunteers
No

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

Arms & Interventions

Intervention arm

Active Comparator

House dust-mite SLIT

Intervention: House dust-mite SLIT (Drug)

Control arm

Placebo Comparator

Normal saline

Intervention: Normal saline (Drug)

Outcomes

Primary Outcomes

Clinical Asthma - parental questionnaire

Time Frame: Age 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 reversibility

Time Frame: 6 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 Outcomes

  • Asthma comparison(Age 6 years)
  • Bronchial hyper-responsiveness(Age 6 years)
  • Cumulative sensitization(Age 6 years)
  • Cumulative aeroallergen sensitization(Age 6 years)
  • Clinical atopic disease- parental questionnaire(Age 6 years)
  • Airway inflammation level- exhaled nitric oxide measurement(Age 6 years)
  • House dust-mite sensitization(Age 6 years)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (2)

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