Using Commonly Available Food Products To Treat Food Allergy

University of Southampton216 enrolled

Overview

Food allergy affects 1 in 30 children, and is the commonest trigger for life-threatening reactions (anaphylaxis) in this age group. It is a major public health issue, with practical implications for industry, education and healthcare systems. Oral immunotherapy (OIT) is an emerging treatment option, where small, increasing doses of a food allergen are used to cause "desensitisation", so food-allergic individuals no longer have symptoms when exposed to the trigger food. However, frequent allergic reactions during OIT (including anaphylaxis) are common, and can lead to patients having to stop treatment. In addition, food-allergic children usually dislike the taste of the food they are allergic too, which affects compliance and treatment success. There is a lack of longer-term data to inform cost-effectiveness analyses for OIT. The NATASHA study will recruit young people from age 6+ years with IgE-mediated peanut allergy, and young people aged 3+ years with IgE-mediated allergy to cow's milk, who will undergo oral immunotherapy for these allergens using real-world foods (taken carefully according to a standardised protocol under medical supervision). In addition to assessing efficacy and safety outcomes, we will also collect longer-term data to evaluate cost-effectiveness in the UK setting.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

216

Conditions

IgE-Mediated Cow Milk Allergy

Eligibility

Sex: ALLMin age: 3 YearsMax age: 23 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 6-23 years with IgE-mediated peanut allergy, or age 3-23 years with IgE-mediated food allergy to cow's milk 2. Past history consistent with IgE-mediated allergy to the relevant allergen 3. Allergic to cumulative ≤1.44 g protein (of the specific allergen) at baseline DBPCFC, prior to treatment allocation 4. Written informed consent (for young people under 16, consent from the parent/legal guardian (AND assent from the young person when the young person is age 6+ years) Exclusion Criteria: 1. Required previous admission to an intensive care unit for management of an allergic reaction 2. Clinically significant chronic illness (other than asthma, rhinitis or eczema) 3. Moderate-severe eczema, defined as requiring more than once daily application of 1% hydrocortisone or equivalent topical calcineurin inhibitor as maintenance treatment despite appropriate use of emollients (eczema is not otherwise an exclusion criteria) 4. Poorly controlled asthma within the previous 3 months (as defined by clinician judgement with reference to the International Consensus On (ICON) Pediatric Asthma consensus), or asthma requiring treatment with \>5 days oral corticosteroids within the previous 3 months 5. Previous history of eosinophilic oesophagitis 6. Undergoing subcutaneous or sublingual immunotherapy to respiratory allergens, and not yet established on maintenance dosing for at least 6 months 7. Undergoing allergen immunotherapy for food allergy and within the first year of treatment 8. In CM-allergic children under consideration for desensitisation to CM: * currently consuming CM-containing products other than extensively-heated milk in baked foods (e.g. biscuits, cakes) * significant symptoms of non-IgE-mediated CM allergy within the previous 12 months 9. Taking prebiotic or probiotic supplements and unwillingness to discontinue 10. Subjects receiving anti-IgE therapy, oral immunosuppressants, beta-blocker or Angiotensin Converting Enzyme (ACE) inhibitor 11. Tolerance to cumulative ≥1.44 g food protein at initial DBPCFC during screening 12. Objective allergic reaction to ≤4mg cow's milk protein or ½ Reese's puff in peanut-allergic children, during screening 13. Objective reaction to the placebo at screening DBPCFC 14. Past or current medical issue, participation in another clinical trial or other consideration, which, in the opinion of the investigator, may pose additional risks from study participation, interfere with compliance or otherwise impact on the quality or interpretation of study data 15. Pregnancy 16. Direct personal or commercial relationship with a member of the local study team directly involved with the conduct of the trial 17. Unwilling or unable to fulfil study requirements, including the requirement for appropriate supervision following dosing at home)

Outcomes

Primary Outcomes

Efficacy and effectiveness

The proportion of participants in intervention arms (combined) versus control arm (by allergen) who, following 9-12 months of OIT (or standard care, for controls): * tolerate at least 1 gram of food protein (discrete dose, approximately 4-6 peanuts, or 30ml of CM) AND * demonstrate a minimum 10-fold increase in the maximum tolerated dose (defined as the highest dose not causing dose-limiting symptoms) at the end-of-updosing double-blind, placebo-controlled food challenge (DBPCFC), compared to baseline DBPCFC

Time frame: 9-12 months

Secondary Outcomes

Safety: adverse events

i. Proportion of participants experiencing study-related adverse events (excluding mild, transient oropharyngeal symptoms) in active vs control arms, by allergen ii. Other safety outcomes: rate of anaphylaxis (and adrenaline \[epinephrine\] use), withdrawals due to intervention, by allergen iii. Adverse events (excluding mild, transient oropharyngeal symptoms) specifically occurring at updosing visits, in the home versus in-hospital updosing groups, by allergen

Time frame: 24 months

Health-related quality of life (HRQL) as assessed by the Food Allergy Quality of Life Questionnaire (FAQLQ)

Change in HRQL score assessed using validated questionnaire (Food Allergy Quality of Life Questionnaires (FAQLQ), from baseline at the following timepoints post allocation: 3, 6, end of induction (9-12 months), 18 and 24 months, in i. Participants ii. Parent/carers (if participants aged ≤17 years) The tools to be used are: \- FAQLQ: as per Muraro et al, Allergy 2014; 69:845-853. A higher score is associated with a greater impact on quality of life, as per the cited reference.

Time frame: 24 months

Health-related quality of life (HRQL) as assessed by EQ5D

Change in quality of life assessment assessed using EQ5D, from baseline at the following timepoints post allocation: 3, 6, end of induction (9-12 months), 18 and 24 months, in i. Participants ii. Parent/carers (if participants aged ≤17 years) The tools to be used are: \- EQ5D: a standardised measure of health-related quality of life developed by the EuroQol Group to provide a simple, generic questionnaire for use in clinical and economic appraisal and population health surveys (see https://euroqol.org/ for detailed instructions on use)

Time frame: 24 months

Health-related quality of life (HRQL) as CHU9D

Change in quality of life assessment assessed using CHU9D, from baseline at the following timepoints post allocation: 3, 6, end of induction (9-12 months), 18 and 24 months, in i. Participants ii. Parent/carers (if participants aged ≤17 years) The tools to be used are: \- CHU9D - a paediatric generic preference-based measure of health-related quality of life suitable for 7 to 17 year olds. (see https://licensing.sheffield.ac.uk/product/CHU-9D for detailed instructions on use)

Time frame: 24 months

Adherence to dietary avoidance

Adherence to dietary avoidance between intervention and control arms (by allergen, and between allergens) as determined by number of accidental reactions reported by each participant, during the duration of the study

Time frame: 24 months

Adherence to treatment

Adherence to daily OIT dosing by allergen, expressed as a the proportion of doses taken divided by the number of doses which should have been taken by each participant.

Time frame: 24 months

Immunological outcomes: change in skin prick test wheal

Change in immunological measures (skin prick test wheal (mm diameter) to commercial allergen extract, performed according to national guidelines) at baseline vs 12 months vs 24 months, between active and control arms (by allergen)

Time frame: 24 months

Immunological outcomes: change in allergen-specific serum antibody profile

Change in immunological measures (specific Immunoglobulin E (IgE) to specific allergen) measured by ImmunoCAP (kUA/l) at baseline vs 12 months vs 24 months, between active and control arms (by allergen)

Time frame: 24 months

Using Commonly Available Food Products To Treat Food Allergy

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts