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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04801823




Registration number
NCT04801823
Ethics application status
Date submitted
12/03/2021
Date registered
17/03/2021
Date last updated
17/09/2021

Titles & IDs
Public title
The TreEat Study- Can Early Introduction of Tree Nuts Prevent Tree Nut Allergy in Infants With Peanut Allergy
Scientific 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
Secondary ID [1] 0 0
70489
Universal Trial Number (UTN)
Trial acronym
TreEat
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Food Allergy in Infants 0 0
Nut Allergy 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Home introduction
Other interventions - Multi Nut oral food challenge

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.

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 interventions: Home introduction
Cautious, graded introduction of individual tree nuts

Other interventions: Multi Nut oral food challenge
In hospital multi nut oral food challenge (almond, cashew, hazelnut, walnut)

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
18 months of age
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
18 months of age
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
18 months of age
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
18 months of age
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
18 months of age
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
18 months of age
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline and 18 months of age
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline and 18 months of age
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
18 months of age

Eligibility
Key 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)
Minimum age
4 Months
Maximum age
11 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute (MCRI) - Melbourne
Recruitment postcode(s) [1] 0 0
3052 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04801823
Trial related presentations / 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.
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.
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. Review.
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.
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.
Lange L, Lasota L, Finger A, Vlajnic D, Büsing 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.
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.
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.
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. Review.
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.
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.
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.
van der Valk JPM, Bouche RE, Gerth van Wijk R, de Groot H, Wichers HJ, Dubois AEJ, de Jong NW. Low percentage of clinically relevant pistachio nut and mango co-sensitisation in cashew nut sensitised children. Clin Transl Allergy. 2017 Mar 20;7:8. doi: 10.1186/s13601-017-0145-z. eCollection 2017.
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.
Zahradnik E, Raulf M. Respiratory Allergens from Furred Mammals: Environmental and Occupational Exposure. Vet Sci. 2017 Aug 4;4(3). pii: E38. doi: 10.3390/vetsci4030038. Review.
Public notes

Contacts
Principal investigator
Name 0 0
Kirsten Perrett, MD. PhD
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Vicki McWilliam, MND.PhD
Address 0 0
Country 0 0
Phone 0 0
+61393457660
Fax 0 0
Email 0 0
vicki.mcwilliam@mcri.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04801823