Using Commonly Available Food Products To Treat Food Allergy (NATASHA)

Using Commonly Available Food Products To Treat Food Allergy (NATASHA Study)

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 Overview

• Status: Recruiting
• Conditions: Peanut Allergy; IgE-Mediated Cow Milk Allergy
• Intervention / Treatment: Other: Peanut in common foods or supermarket-sourced cow's milk (CM)

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hasan Arshad, MBBS DM FRCP; Phone Number: 44 23 8120 5232; Email: p.turner@imperial.ac.uk

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • Recruiting
    • University of Hospitals of Leicester NHS Trust
  • London, United Kingdom
    • Recruiting
    • Imperial College Healthcare NHS Trust
  • Newcastle, United Kingdom
    • Not yet recruiting
    • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Sheffield, United Kingdom
    • Recruiting
    • Sheffield Children's Hospital NHS Foundation Trust
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Immunotherapy, in-hospital supervision for updosing; Active oral immunotherapy, with all updosing visits taking place in hospital	Other: Peanut 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
Experimental: Oral Immunotherapy, virtual supervision for updosing; Active oral immunotherapy, with all updosing visits taking place with virtual supervision	Other: Peanut 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
No Intervention: Control arm: allergen avoidance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	9-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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)	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)	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	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.	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)	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)	24 months

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: Imperial College London; Natasha Allergy Research Foundation
• Investigators: Principal Investigator: Paul J Turner, FRCPCH PhD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Milk Hypersensitivity; Peanut Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: ERGO 71012; IRAS ID 310316 (Other Identifier: NHS Human Research Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified data may be available upon request to the Chief Investigators, subject to local data protection legislation.

Drug and device information, study documents

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