Multi-Food Oral Immunotherapy for Peanut and Tree Nuts
An Open-Label, Multicenter, Randomized Clinical Trial Evaluating the Efficacy and Safety of Oral Multi-Food Immunotherapy With Peanut and Tree Nuts Protein Mixtures
- Registry ID
- NCT07764159
- Source registry
- NCT
- Status
- NOT_YET_RECRUITING
- Phase
- NA
- Study type
- INTERVENTIONAL
- Sponsor
- Medical University of Warsaw
- Enrollment
- 39
- Start date
- 2026-09-01
- Completion date
- 2031-12-01
- Last update
- 2026-08-13
Conditions
- Oral Immunotherapy for Food Allergy
- Peanut Allergies
- Tree Nut Allergies
- Food Allergy in Children
- Food Allergies
Summary
This study aims to evaluate the efficacy and safety of multi-food oral immunotherapy (multi-OIT) using peanut and tree nuts proteins in children with confirmed food allergy to at least two allergens. Participants will be randomized in a 2:1 ratio to receive either multi-OIT or standard management consisting of an elimination diet. The primary objective is to evaluate immunotherapy efficacy defined as achieving tolerance to a cumulative dose of 4444 mg of protein during an oral food challenge (OFC-2) for at least one allergen that elicited a reaction during baseline challenge (OFC-1), compared with the control group. Secondary outcomes include the proportion of participants tolerating multiple allergens at the target cumulative dose; the incidence, type, and severity of adverse events classified according to the World Allergy Organization (WAO) grading system; changes in immunological parameters, including allergen-specific IgE and IgG4 levels; changes in skin prick test responses; changes in the quality of life of patients and their families.
Detailed description
This is an interventional, open-label, multicenter, randomized clinical trial enrolling 39 children aged 1-12 years with confirmed allergy to at least two of the following allergens: peanut, cashew, walnut, hazelnut and almond.
Participants will be randomized in a 2:1 ratio to either the experimental group receiving multi-food oral immunotherapy (multi-OIT) or the control group receiving standard of care consisting of an elimination diet and rescue medications. Multi-OIT will be administered using a standardized mixture of peanut and tree nuts proteins, with a dose-escalation phase followed by a maintenance phase targeting 300 mg of protein per allergen per day. Treatment duration will be approximately 18 months.
All participants will undergo oral food challenges at baseline (OFC-1) and at the end of the study (OFC-2). The primary efficacy endpoint is defined as the proportion of participants achieving tolerance to a cumulative dose of 4444 mg of protein during OFC-2 for at least one allergen that elicited a reaction during OFC-1, compared with the control group. Safety will be monitored throughout the study based on adverse events recorded in symptom diaries and classified according to established grading systems.
Secondary outcomes include the proportion of participants tolerating multiple allergens at the target cumulative dose, the frequency and severity of adverse events classified according to the World Allergy Organization (WAO) grading system, changes in immunological parameters (including allergen-specific IgE and IgG4), skin prick test responses and quality of life of patients and their families.
Participants in the control group will be offered the option to receive immunotherapy after completion of the study.
Interventions
- OTHER: Standard of Care (Elimination Diet)
- OTHER: Multi-Food Oral Immunotherapy (Multi-OIT) with Peanut and Tree Nuts Proteins
Inclusion criteria
Inclusion Criteria:
* Age 1-12 years;
* Confirmed allergy to at least two allergens included in the protocol, i.e., peanut and/or tree nuts: cashew, walnut, hazelnut, and almond;
* Positive skin prick test (SPT) (wheal diameter ≥ 3 mm) and/or specific IgE (sIgE) level \> 0.35 kUA/L for at least two of the analyzed allergens;
* Positive OFC-1 (oral food challenge) of grade I-IV according to the WAO classification for at least two allergens, with a positive reaction occurring after administration of a dose ≥ 3 mg and ≤ 3000 mg of allergen protein;
* Participants may be enrolled based on the abbreviated procedure as outlined in the study description;
* Written informed consent obtained from a legal guardian, and, where applicable, assent from the child in accordance with their age and level of maturity;
* Good prognosis for compliance and cooperation of the patient and their caregivers.
Exclusion criteria
Exclusion Criteria:
* Allergic reaction at the lowest challenge dose of 1 mg of allergen protein for any allergen, or no allergic reaction after administration of the maximum dose of 3000 mg of allergen protein for at least four of the analyzed allergens;
* History of anaphylaxis with a grade V reaction according to the WAO classification, either during an oral food challenge or in the patient's medical history;
* Severe asthma;
* Poorly controlled asthma according to GINA 2025 (lack of symptom control and/or ≥2 exacerbations requiring systemic glucocorticoids or ≥1 exacerbation requiring hospitalization within the last 12 months), or in children able to perform spirometry: FEV1 \< -1.64 Z-score and/or FEV1/FVC \< -1.64 Z-score;
* Eosinophilic gastrointestinal disease;
* Other chronic diseases requiring ongoing treatment which, in the investigator's opinion, may increase the risk associated with study participation or interfere with the interpretation of results, including severe cardiac disease, epilepsy, metabolic disorders, or diabetes;
* Previous immunotherapy with food allergens;
* Concurrent immunotherapy with aeroallergens;
* Treatment with biologic agents, beta-blockers, ACE inhibitors, or calcium channel blockers;
* Oral corticosteroid therapy meeting any of the following criteria: daily treatment for \>1 month within the last 12 months; at least two courses lasting ≥7 days within the last 12 months; one course lasting ≥7 days within the last 3 months;
* Lack of consent to participate in the study or insufficient cooperation of the patient and/or caregivers. In such cases, patients will receive standard medical care, including allergen avoidance and provision of emergency medication.
Well-controlled asthma, allergic rhinitis, and atopic dermatitis are not exclusion criteria.
Primary outcomes
[{"measure":"Immunotherapy Efficacy","timeFrame":"Up to 21 months after starting oral immunotherapy"}]
Locations
- Department of Pediatrics, Children's Diseases Clinic, Jagiellonian University Medical Colleg, Division of Pulmonology, Allergology and Dermatology, University Children's Hospital in Kraków, Krakow, Poland
- Department of Paediatric Pulmonology and Allergology, Medical University of Warsaw, Warsaw, Poland
- Allergy Unit, Department of Pulmonary Diseases, Children's Hospital in Dziekanów Leśny, Dziekanów Leśny, Poland
- Department of Pediatric Pulmonology, Allergology and Clinical Immunology, Institute of Pediatrics, Karol Jonscher Clinical Hospital, Poznań University of Medical Sciences, Poznan, Poland
Publications
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- Lodge CJ, Waidyatillake N, Peters RL, Netting M, Dai X, Burgess J, Hornung CJ, Perrett KP, Tang MLK, Koplin JJ, Dharmage SC. Efficacy and safety of oral immunotherapy for peanut, cow's milk, and hen's egg allergy: A systematic review of randomized controlled trials. Clin Transl Allergy. 2023 Jul;13(7):e12268. doi: 10.1002/clt2.12268.
- Erdle SC, Cook VE, Cameron SB, Yeung J, Kapur S, McHenry M, Chan ES, Mak R, Rex GA, Wong T, Soller L. Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy. J Allergy Clin Immunol Pract. 2023 Apr;11(4):1177-1183. doi: 10.1016/j.jaip.2023.01.031. Epub 2023 Feb 1.
- Begin P, Winterroth LC, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, Trela A, Hoyte E, O'Riordan G, Seki S, Blakemore A, Woch M, Hamilton RG, Nadeau KC. Safety and feasibility of oral immunotherapy to multiple allergens for food allergy. Allergy Asthma Clin Immunol. 2014 Jan 15;10(1):1. doi: 10.1186/1710-1492-10-1.
- Pasioti M, Xepapadaki P, Mathioudakis AG, Lakoumentas J, Efstathiou E, Papadopoulos NG. Current options in the management of tree nut allergy: A systematic review and narrative synthesis. Pediatr Allergy Immunol. 2024 May;35(5):e14132. doi: 10.1111/pai.14132.
- Upton JEM, Li CH, Berenjy A, Galper A, Yin X, Celik A, Duan L, Wong S, Ditlof CM, San Diego KE, Hoang JA, Ben-Shoshan M, Kothari A, Hung L, Monteiro M, Phue WH, Moraes TJ, Eiwegger T. Safety and Efficacy of Very Low-Dose Multi-Nut Oral Immunotherapy in Children. Clin Transl Allergy. 2025 Dec;15(12):e70125. doi: 10.1002/clt2.70125.
- Sampson HA, Arasi S, Bahnson HT, Ballmer-Weber B, Beyer K, Bindslev-Jensen C, Bird JA, Blumchen K, Davis C, Ebisawa M, Nowak-Wegrzyn A, Patel N, Peters RL, Sicherer S, Spergel J, Turner PJ, Yanagida N, Eigenmann PA. AAAAI-EAACI PRACTALL: Standardizing oral food challenges-2024 Update. Pediatr Allergy Immunol. 2024 Nov;35(11):e14276. doi: 10.1111/pai.14276.
- Chojnowska-Wojtowicz M, Lyzwa K, Zielinska J, Zagorska W, Grzela K. Prevalence of nut allergen sensitization among children in central Poland. Postepy Dermatol Alergol. 2023 Feb;40(1):40-46. doi: 10.5114/ada.2022.124730. Epub 2023 Feb 27.
- Jones SM, Kim EH, Nadeau KC, Nowak-Wegrzyn A, Wood RA, Sampson HA, Scurlock AM, Chinthrajah S, Wang J, Pesek RD, Sindher SB, Kulis M, Johnson J, Spain K, Babineau DC, Chin H, Laurienzo-Panza J, Yan R, Larson D, Qin T, Whitehouse D, Sever ML, Sanda S, Plaut M, Wheatley LM, Burks AW; Immune Tolerance Network. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022 Jan 22;399(10322):359-371. doi: 10.1016/S0140-6736(21)02390-4.
- Brough HA, Caubet JC, Mazon A, Haddad D, Bergmann MM, Wassenberg J, Panetta V, Gourgey R, Radulovic S, Nieto M, Santos AF, Nieto A, Lack G, Eigenmann PA. Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study. J Allergy Clin Immunol. 2020 Apr;145(4):1231-1239. doi: 10.1016/j.jaci.2019.09.036. Epub 2019 Dec 20.
- Andorf S, Manohar M, Dominguez T, Block W, Tupa D, Kshirsagar RA, Sampath V, Chinthrajah RS, Nadeau KC. Feasibility of sustained response through long-term dosing in food allergy immunotherapy. Allergy Asthma Clin Immunol. 2017 Dec 21;13:52. doi: 10.1186/s13223-017-0224-7. eCollection 2017.
- Lyons SA, Clausen M, Knulst AC, Ballmer-Weber BK, Fernandez-Rivas M, Barreales L, Bieli C, Dubakiene R, Fernandez-Perez C, Jedrzejczak-Czechowicz M, Kowalski ML, Kralimarkova T, Kummeling I, Mustakov TB, Papadopoulos NG, Popov TA, Xepapadaki P, Welsing PMJ, Potts J, Mills ENC, van Ree R, Burney PGJ, Le TM. Prevalence of Food Sensitization and Food Allergy in Children Across Europe. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2736-2746.e9. doi: 10.1016/j.jaip.2020.04.020. Epub 2020 Apr 21.
- Nguyen K, Lewis MO, Hanna E, Alfaro MKC, Corrigan K, Buonanno J, Datta R, Brown-Whitehorn T, Spergel JM, Cianferoni A. Safety of Multifood Oral Immunotherapy in Children Aged 1 to 18 Years at an Academic Pediatric Clinic. J Allergy Clin Immunol Pract. 2023 Jun;11(6):1907-1913.e1. doi: 10.1016/j.jaip.2023.03.002. Epub 2023 Mar 10.
- Upton JEM, Toscano-Rivero D, Ke D, Berenjy A, Lejtenyi D, Beaudette L, Yin X, Li CH, Duan LY, Cohen CG, Kim V, Marzouk S, Grunebaum E, McCusker CT, Mazer B, Eiwegger T, Ben-Shoshan M. Peanut Oral Immunotherapy Using 30 and 300 mg Maintenance Doses. J Allergy Clin Immunol Pract. 2026 Jan;14(1):223-232.e7. doi: 10.1016/j.jaip.2025.10.007. Epub 2025 Oct 16.
- Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Carr S, Custovic A, Durham S, Ebisawa M, Geller M, Gonzalez-Estrada A, Greenberger PA, Hossny E, Irani C, Leung ASY, Levin ME, Muraro A, Oppenheimer JJ, Ortega Martell JA, Pouessel G, Rial MJ, Senna G, Tanno LK, Wallace DV, Worm M, Morais-Almeida M; WAO Anaphylaxis Committee and WAO Allergen Immunotherapy Committee. Updated grading system for systemic allergic reactions: Joint Statement of the World Allergy Organization Anaphylaxis Committee and Allergen Immunotherapy Committee. World Allergy Organ J. 2024 Feb 10;17(3):100876. doi: 10.1016/j.waojou.2024.100876. eCollection 2024 Mar.
- Huang J, Puglisi LH, Cook KA, Kelso JM, Wangberg H. Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting. J Allergy Clin Immunol Pract. 2025 Jan;13(1):185-191.e3. doi: 10.1016/j.jaip.2024.09.025. Epub 2024 Sep 30.
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