IgE-Mediated Cow Milk Allergy, Peanut Allergy
Conditions
Brief summary
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.
Interventions
OTHERPeanut in common foods or supermarket-sourced cow's milk (CM)
Participants will be given a set dose of peanut (e.g. peanut-containing cereal, whole peanuts) or cow's milk to take on a daily basis, as per protocol
Sponsors
University of Southampton
Imperial College London
Natasha Allergy Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcomes assessed by double-blind, placebo-controlled food challenge
Intervention model description
Parallel arm, with cross-over for those allocated to control group only following determination of primary outcome
Eligibility
Sex/Gender
ALL
Age
3 Years to 23 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy and effectiveness | 9-12 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological outcomes: change in skin prick test wheal | 24 months | 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) |
| Safety: adverse events | 24 months | 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 |
| Health-related quality of life (HRQL) as assessed by the Food Allergy Quality of Life Questionnaire (FAQLQ) | 24 months | 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. |
| Health-related quality of life (HRQL) as assessed by EQ5D | 24 months | 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) |
| Health-related quality of life (HRQL) as CHU9D | 24 months | 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) |
| Adherence to dietary avoidance | 24 months | 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 |
| Immunological outcomes: change in allergen-specific serum antibody profile | 24 months | 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) |
| Adherence to treatment | 24 months | 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. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORPaul J Turner, FRCPCH PhD
Imperial College London
Outcome results
None listed