The TreEat Study- Can Early Introduction of Tree Nuts Prevent Tree Nut Allergy in Infants With Peanut Allergy
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Home Introduction of Individual tree nuts 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
Cautious, graded introduction of individual tree nuts
|
| Experimental: In hospital multi-tree nut (almond, cashew hazelnut and walnut) oral food challenge (OFC) 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
In hospital multi nut oral food challenge (almond, cashew, hazelnut, walnut)
|
Outcome Measures
Primary Outcome Measures
- Difference between the two treatment arms in the proportion of participants with clinical confirmed tree nut allergy at 18 months of age [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.
Secondary Outcome Measures
- Difference between the two treatment arms in the proportion of participants with ongoing peanut allergy at 18 months of age [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
- Difference between the two treatment arms in the proportion and severity of reported adverse events (AE) related to tree nut ingestion. [18 months of age]
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.
- Difference between the two treatment arms in the proportion and severity of solicited AEs related to tree nut ingestion. [18 months of age]
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.
- Difference between the 2 treatment arms in the number of tree nuts ingested. [18 months of age]
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.
- Difference between the 2 treatment arms in the frequency of tree nuts ingested. [18 months of age]
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.
- 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. [Baseline and 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
- Difference between the two treatment arms in the mean change from baseline in State/Trait anxiety scores using the State/Trait Anxiety Inventory [Baseline and 18 months of age]
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.
- Difference in the number of allergy-related healthcare visits from randomization to 18 months of age between the treatment arms [18 months of age]
Captured per number of hospitalizations, Emergency room (ER) visits, physician office visits, and medications / number of prescriptions from randomization to 18 months of age.
Eligibility Criteria
Criteria
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.
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Pre-existing tree nut allergy (parent-reported).
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Any tree nut already tolerated (ingestion on >3 occasions without reaction of around 1 teaspoon)
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SPT or sIgE performed to any tree nuts
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Not commenced or unable to eat solid food
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Prescribed beta-blocker medication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Murdoch Children's Research Institute (MCRI) | Melbourne | Victoria | Australia | 3052 |
Sponsors and Collaborators
- Murdoch Childrens Research Institute
Investigators
- Principal Investigator: Kirsten Perrett, MD. PhD, Murdoch Children's Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
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- Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012 Dec;130(6):1260-74. doi: 10.1016/j.jaci.2012.10.017.
- Savvatianos S, Konstantinopoulos AP, Borgå Å, Stavroulakis G, Lidholm J, Borres MP, Manousakis E, Papadopoulos NG. Sensitization to cashew nut 2S albumin, Ana o 3, is highly predictive of cashew and pistachio allergy in Greek children. J Allergy Clin Immunol. 2015 Jul;136(1):192-4. doi: 10.1016/j.jaci.2015.03.037. Epub 2015 May 8.
- Soriano VX, Peters RL, Ponsonby AL, Dharmage SC, Perrett KP, Field MJ, Knox A, Tey D, Odoi S, Gell G, Camesella Perez B, Allen KJ, Gurrin LC, Koplin JJ. Earlier ingestion of peanut after changes to infant feeding guidelines: The EarlyNuts study. J Allergy Clin Immunol. 2019 Nov;144(5):1327-1335.e5. doi: 10.1016/j.jaci.2019.07.032. Epub 2019 Aug 8.
- Thalayasingam M, Noble V, Franzmann A, O'Sullivan M. Outcome of mixed nut biscuit challenges in low-risk patients who are on tree nut exclusion diet. Pediatr Allergy Immunol. 2015 Nov;26(7):682-4. doi: 10.1111/pai.12437. Epub 2015 Sep 11.
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- Van Erp FC, Knulst AC, Kok IL, van Velzen MF, van der Ent CK, Meijer Y. Usefulness of open mixed nut challenges to exclude tree nut allergy in children. Clin Transl Allergy. 2015 May 16;5:19. doi: 10.1186/s13601-015-0062-y. eCollection 2015.
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