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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Immunotherapy; Allergy and Immunology
• Intervention / Treatment: Drug: House dust-mite SLIT; Drug: Normal saline

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 Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust
  • Isle Of White
    • Newport, Isle Of White, United Kingdom, PO30 5TG
      • David Hyde Asthma and Allergy Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 9 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention arm; House dust-mite SLIT	Drug: House dust-mite SLIT; received 2000 standard treatment units of glycerinated HDM allergen extract (ALK-AbellÓ) per day. Normal saline was administered to the placebo group. 11 µg of HDM allergen (equal parts of Dermatophagoides pteronyssinus and Dermatophagoides farinae) administered twice daily as oral drops.; Other Names: glycerinated HDM allergen extract (ALK-AbellÓ)
Placebo Comparator: Control arm; Normal saline	Drug: Normal saline; Normal saline administered in same frequency and manner as intervention; Other Names: Normal saline placebo control
No Intervention: Observation cohort; ITEC observational cohort, no intervention administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Asthma - parental questionnaire	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.	Age 6 years
Clinical Asthma- spirometry with reversibility	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).	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchial hyper-responsiveness	Comparison of bronchial hyperresponsiveness, as determined by methacholine bronchial allergen challenge, at age 6 years.	Age 6 years
Asthma comparison	Comparison of asthma, as defined by wheeze plus bronchial hyperreactivity	Age 6 years
Airway inflammation level- exhaled nitric oxide measurement	Comparison of airway inflammation level, as assessed by exhaled nitric oxide, between placebo and intervention group age 6 years	Age 6 years
Cumulative sensitization	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.	Age 6 years
Cumulative aeroallergen sensitization	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.	Age 6 years
House dust-mite sensitization	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.	Age 6 years
Clinical atopic disease- parental questionnaire	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	Age 6 years

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: Isle of Wight NHS Trust
• Investigators: Principal Investigator: Graham Roberts, Prof, University of Southampton

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2017
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): January 15, 2019

Study Registration Dates

• First Submitted: November 22, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Early childhood; Sublingual immunotherapy; Atopy; House Dust-mite
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: Southampton CHI0808

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No