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Food Allergy in InfantsPhase 3TreEatNCT04801823

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

A Phase 3 study testing Home introduction and Multi Nut oral food challenge in people with Food Allergy in Infants and Nut Allergy, run by Murdoch Childrens Research Institute at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 to 11 months
Conditions the study is for
Food Allergy in Infants, Nut Allergy
What is being tested?
Home introduction and Multi Nut oral food challenge
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
212 participants
Where
1 siteAustralia
Study dates
1 Jun 2021to 29 Jun 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 11 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Murdoch Children's Research Institute (MCRI)

    Melbourne, Victoria, 3052

Other trials in Australia

About this study

Official title: 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

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.

Being tested
Home introduction, Multi Nut oral food challenge
Keywords
food allergy, nut allergy
Medical subject headings
Nut Hypersensitivity, Food Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Home introductionOther

    Cautious, graded introduction of individual tree nuts

  • Multi Nut oral food challengeOther

    In hospital multi nut oral food challenge (almond, cashew, hazelnut, walnut)

Study groups in NCT04801823
Study groupRoleWhat they receive
Home Introduction of Individual tree nutsActive comparatorCurrent 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.
Receives: Other: Home introduction
In hospital multi-tree nut (almond, cashew hazelnut and walnut) oral food challenge (OFC)ExperimentalInfant 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.
Receives: Other: Multi Nut oral food challenge

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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:

    1. 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
    2. 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.
    3. Inconclusive -has an unknown outcome as ingestion has not occurred and participant declines OFC.

    Measured: 18 months of age

Secondary outcomes (8)

  1. 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

    Measured: 18 months of age

  2. 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.

    Measured: 18 months of age

  3. 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.

    Measured: 18 months of age

  4. 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.

    Measured: 18 months of age

  5. 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.

    Measured: 18 months of age

  6. 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

    Measured: Baseline and 18 months of age

  7. 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.

    Measured: Baseline and 18 months of age

  8. 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.

    Measured: 18 months of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2021
  2. Study start1 Jun 2021
  3. Primary completion29 Jun 2025
  4. Study completion29 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
212 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04801823
Sponsor's protocol ID
70489
Acronym
TreEat
Status last verified
Feb 2026
First submitted
12 Mar 2021
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The de-identified data set collected for this analysis of the TreEat trial will be available six months after publication of the primary outcome. The study protocol may be obtained from the Murdoch Children's Research Institute. Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the TreEat trial investigators must see and approve the analysis plan describing how the data will be analyzed, there must be an agreement around appropriate acknowledgment and any additional costs involved must be covered. Should the study investigators be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognized research institute which has approved the proposed analysis plan.

Publications

  • Ball H, Luyt D, Bravin K, Kirk K. Single nut or total nut avoidance in nut allergic children: outcome of nut challenges to guide exclusion diets. Pediatr Allergy Immunol. 2011 Dec;22(8):808-12. doi: 10.1111/j.1399-3038.2011.01191.x. Epub 2011 Sep 19.

    PubMed 21929602

  • Cifuentes L, Vosseler S, Blank S, Seismann H, Pennino D, Darsow U, Bredehorst R, Ring J, Mempel M, Spillner E, Ollert MW. Identification of Hymenoptera venom-allergic patients with negative specific IgE to venom extract by using recombinant allergens. J Allergy Clin Immunol. 2014 Mar;133(3):909-10. doi: 10.1016/j.jaci.2013.09.047. Epub 2013 Nov 28. No abstract available.

    PubMed 24290287

  • Dang TD, Mills CE, Allen KJ. Determination of the clinical egg allergy phenotypes using component-resolved diagnostics. Pediatr Allergy Immunol. 2014 Nov;25(7):639-43. doi: 10.1111/pai.12301. Epub 2014 Nov 25.

    PubMed 25376255

  • Dang TD, Tang M, Choo S, Licciardi PV, Koplin JJ, Martin PE, Tan T, Gurrin LC, Ponsonby AL, Tey D, Robinson M, Dharmage SC, Allen KJ; HealthNuts study. Increasing the accuracy of peanut allergy diagnosis by using Ara h 2. J Allergy Clin Immunol. 2012 Apr;129(4):1056-63. doi: 10.1016/j.jaci.2012.01.056. Epub 2012 Mar 3.

    PubMed 22385632

  • Ierodiakonou D, Garcia-Larsen V, Logan A, Groome A, Cunha S, Chivinge J, Robinson Z, Geoghegan N, Jarrold K, Reeves T, Tagiyeva-Milne N, Nurmatov U, Trivella M, Leonardi-Bee J, Boyle RJ. Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis. JAMA. 2016 Sep 20;316(11):1181-1192. doi: 10.1001/jama.2016.12623.

    PubMed 27654604

  • Lange L, Lasota L, Finger A, Vlajnic D, Busing S, Meister J, Broekaert I, Pfannenstiel C, Friedrichs F, Price M, Trendelenburg V, Niggemann B, Beyer K. Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children. Allergy. 2017 Apr;72(4):598-603. doi: 10.1111/all.13050. Epub 2016 Nov 17.

    PubMed 27644013

  • McWilliam V, Peters R, Tang MLK, Dharmage S, Ponsonby AL, Gurrin L, Perrett K, Koplin J, Allen KJ; HealthNuts investigators. Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort. J Allergy Clin Immunol. 2019 Feb;143(2):644-650.e5. doi: 10.1016/j.jaci.2018.07.038. Epub 2018 Aug 30.

    PubMed 30171872

  • Mullins RJ, Wainstein BK, Barnes EH, Liew WK, Campbell DE. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy. 2016 Aug;46(8):1099-110. doi: 10.1111/cea.12748. Epub 2016 May 31.

    PubMed 27144664

  • Pablos I, Wildner S, Asam C, Wallner M, Gadermaier G. Pollen Allergens for Molecular Diagnosis. Curr Allergy Asthma Rep. 2016 Apr;16(4):31. doi: 10.1007/s11882-016-0603-z.

    PubMed 27002515

  • Peters RL, Barret DY, Soriano VX, McWilliam V, Lowe AJ, Ponsonby AL, Tang MLK, Dharmage SC, Gurrin LC, Koplin JJ, Perrett KP. No cashew allergy in infants introduced to cashew by age 1 year. J Allergy Clin Immunol. 2021 Jan;147(1):383-384. doi: 10.1016/j.jaci.2020.07.003. Epub 2020 Jul 18. No abstract available.

    PubMed 32693093

  • 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. No abstract available.

    PubMed 23195525

  • Savvatianos S, Konstantinopoulos AP, Borga A, 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. No abstract available.

    PubMed 25959668

  • 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.

    PubMed 31401287

  • 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. No abstract available.

    PubMed 26126774

  • Togias A, Cooper SF, Acebal ML, Assa'ad A, Baker JR Jr, Beck LA, Block J, Byrd-Bredbenner C, Chan ES, Eichenfield LF, Fleischer DM, Fuchs GJ 3rd, Furuta GT, Greenhawt MJ, Gupta RS, Habich M, Jones SM, Keaton K, Muraro A, Plaut M, Rosenwasser LJ, Rotrosen D, Sampson HA, Schneider LC, Sicherer SH, Sidbury R, Spergel J, Stukus DR, Venter C, Boyce JA. Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. J Allergy Clin Immunol. 2017 Jan;139(1):29-44. doi: 10.1016/j.jaci.2016.10.010.

    PubMed 28065278

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Home introduction and Multi Nut oral food challenge in people with Food Allergy in Infants and Nut Allergy, run by Murdoch Childrens Research Institute at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference between the two treatment arms in the proportion of participants with clinical confirmed tree nut allergy at 18 months of age (time frame: 18 months of age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04801823, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.

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