The TreEat Study- Can Early Introduction of Tree Nuts Prevent Tree Nut Allergy in Infants With Peanut Allergy

Study Overview
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Brief Summary
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Early and regular ingestion of the common allergens, peanut and egg has been shown to be an effective allergy prevention strategy. It is not clear whether this is also true of tree nut allergy. Current practice in many Australian allergy clinics for children with peanut allergy (high risk of tree nut allergy), is to advise families to introduce each individual tree nut into their child's diet via a cautious home introduction protocol without prior allergy testing (screening). The safety and effectiveness of an early and regular ingestion strategy for the prevention of tree nut allergy has not been formally evaluated and it is known that around a third of children with peanut allergy develop one or more other nut allergies. This trial is a 2-armed, open-label, randomized, controlled trial (RCT) to assess the safety and efficacy of a supervised hospital based multi-tree nut (almond, cashew, hazelnut and walnut) oral food challenge (OFC) + then home introduction of the remaining tree nuts versus standard care (home introduction of all 8 tree nuts) in infants with peanut allergy to reduce the risk of developing tree nut allergy.

Official Title
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Can Early Introduction of Tree Nuts Prevent Tree Nut Allergy in Infants at High Risk of Tree Nut Allergy: The TreEat Study: a Randomised, Open-label Controlled Trial

Conditions
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Food Allergy in Infants, Nut Allergy

Intervention / Treatment
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* Other: Home introduction
* Other: Multi Nut oral food challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants aged greater than 4 months and less than 11 months of age diagnosed with IgE-mediated peanut allergy in conjunction with a positive SPT (≥3mm) or sIgE (specific immunoglobulin E) (>0.35 kU/L) Exclusion Criteria: Any history of severe food induced anaphylaxis. Defined as reaction requiring 2 doses of intramuscular (IM) adrenaline. Pre-existing tree nut allergy (parent-reported). Any tree nut already tolerated (ingestion on >3 occasions without reaction of around 1 teaspoon) SPT or sIgE performed to any tree nuts Not commenced or unable to eat solid food Prescribed beta-blocker medication

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 11 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Home Introduction of Individual tree nuts<br>Current standard of care which is to advise families of infants diagnosed with peanut allergy to introduce tree nuts individually via a standardized, graded and cautious home introduction protocol. Day 1: smear of nut paste to the inside of lip; Day 2: 1/8 teaspoon; Day 3: 1/4 teaspoon; Day 4: 1/2 teaspoon; Day 5: 1 teaspoon. Repeat process with each individual tree nut. | Other: Home introduction<br>* Cautious, graded introduction of individual tree nuts<br>|
| Experimental: In hospital multi-tree nut (almond, cashew hazelnut and walnut) oral food challenge (OFC)<br>Infant will be booked for a 4-nut butter (Almond, Hazelnut, Walnut, and Cashew) graded and supervised OFC in the allergy clinical trials unit at the Murdoch Children's Research Institute. The nut butter contains a 1g dose of each nut protein in a total weight of 20g. Doses will be administered every 15minutes (1. Smear to inside of lip, 2.1/8 teaspoon, 3.1/4 teaspoon, 4.1/2 teaspoon, 5.1 teaspoon, 6.remainder of 20g nut butter paste) If challenge negative, infants continue home introduction of tree nuts as per written instructions provided. If challenge positive, infants will have additional SPT (for full tree nut panel) and single tree nut OFC as per protocol to determine tolerance/allergic status (and +/- home introduction recommendation) for each tree nut. | Other: Multi Nut oral food challenge<br>* In hospital multi nut oral food challenge (almond, cashew, hazelnut, walnut)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the two treatment arms in the proportion of participants with clinical confirmed tree nut allergy at 18 months of age | Tree nut allergy outcomes at 18 months will be defined as: Allergic - has evidence of tree nut sensitization (SPT>=3mm) and has had a reaction consistent with IgE (immunoglobulin E) mediated food allergy OR positive formal OFC Tree nut tolerant- successfully tolerated the tree nut at home on more than 3 occasions of at least 1 teaspoon of nut per occasion OR has had a negative formal OFC. Inconclusive -has an unknown outcome as ingestion has not occurred and participant declines OFC. | 18 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the two treatment arms in the proportion of participants with ongoing peanut allergy at 18 months of age | Peanut allergy will be defined as peanut sensitization (SPT >=3mm) AND has had a reaction consistent with IgE mediated food allergy since randomization OR positive formal OFC | 18 months of age | 
| Difference between the two treatment arms in the proportion and severity of reported adverse events (AE) related to tree nut ingestion. | Number and severity of adverse events (AE) as assessed by standardised predetermined criteria, related to tree nut ingestion from randomization to 18 months of age collected via parent questionnaire and medical history. | 18 months of age | 
| Difference between the two treatment arms in the proportion and severity of solicited AEs related to tree nut ingestion. | Number and severity of solicited AEs as assessed by standardized predetermined criteria, related to tree nut ingestion from randomization to 18 months of age collected via parent questionnaire and medical history. | 18 months of age | 
| Difference between the 2 treatment arms in the number of tree nuts ingested. | Parent reported tree nut ingestion history based on questionnaire at baseline and 18 months of age. 0-8 tree nuts and the higher the number of tree nuts the better. | 18 months of age | 
| Difference between the 2 treatment arms in the frequency of tree nuts ingested. | Parent reported tree nut ingestion history based on questionnaire at baseline and 18 months of age. Range will be never to daily with higher frequency better. | 18 months of age | 
| Difference between the two treatment arms in mean change from baseline of Quality of Life Scores using the Food Allergy Quality of Life Questionnaire (FAQLQ-PF)- Parent Form at 18 months of age. | The Food Allergy Quality of Life Questionnaires (FAQLQ) are disease-specific health-related quality of life (HRQL) questionnaires for patients with food allergy. FAQLQ-PF (Parent Form), completed by parents of children aged 0-12 years consists of 30 items over 3 domains (emotional impact, food anxiety, social and dietary restrictions). Total and domain scores are calculated by dividing the sum of completed items by the number of completed items. Questions are based on a 6 point Likert scale with higher scores indicating greater impact on quality of life | Baseline and 18 months of age | 
| Difference between the two treatment arms in the mean change from baseline in State/Trait anxiety scores using the State/Trait Anxiety Inventory | The State-Trait Anxiety Inventory (STAI) is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic. The total score ranges from 0-63 with higher scores positively correlated with higher levels of anxiety. | Baseline and 18 months of age | 
| Difference in the number of allergy-related healthcare visits from randomization to 18 months of age between the treatment arms | Captured per number of hospitalizations, Emergency room (ER) visits, physician office visits, and medications / number of prescriptions from randomization to 18 months of age. | 18 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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food allergy, nut allergy