Efficacy of Cashew Nut Protein Immunotherapy

Not Applicable

Recruiting

• Conditions: Food Allergy
• Interventions: Combination Product: Cashew immunotherapy

• Registration Number: NCT06328504
• Lead Sponsor: Medical University of Warsaw

Brief Summary

It is a randomized, single-center, controlled trial to evaluate the effectiveness of oral immunotherapy with cashew protein compared with standard treatment (elimination diet) in pediatric patients with cashew allergy.

Detailed Description

According to Polish data, in the population of children suspected of food allergy, cashew was the third nut found to be allergic, after peanut and hazelnut. Allergic reactions to nuts can be severe and life-threatening, making it challenging to avoid hidden sources of the allergen.

An effective and safe alternative to allergen avoidance strategies may be the use of oral specific immunotherapy.

In this study 39 children, aged 4 to 17 years with a diagnosis of IgE-dependent allergy to cashew, confirmed by an open oral provocation test (OFC; the first provocation before starting oral desensitization), will be randomly (2:1) assigned to two groups. The first group will be desensitized with a maintenance dose - 1200mg of cashew protein, while the second group - the control group - will be offered standard management - avoidance of cashew consumption.

Patients in the control group will be offered immunotherapy at the end of the study if its effectiveness is confirmed.

The desensitization procedure was planned in accordance with the guidelines for immunotherapy in food allergy of the European Academy of Allergology and Clinical Immunology.

The source of cashew protein is flour. The first dose of immunotherapy is given to patients in the intervention group in the hospital ward. The size of the initial dose depends on the symptom-triggering dose during the initial oral food provocation with cashew protein.

Every 2 weeks in the hospital setting, another higher dose of cashew protein will be given to the child. The requirement for increasing the dose of cashew is to achieve full tolerance of the previous dose. The maximum duration of this phase is 60 weeks.

After the maximum dose is tolerated, desensitization will continue for 12 weeks - the maintenance phase of desensitization.

The maintenance dose is 1200mg of cashew protein. The duration of the maintenance phase is 12 weeks (+/-3 weeks). After 12 weeks +/-3 weeks of maintenance dose, OFC and cashew protein tolerance assessment will be performed. Confirmation of complete cashew tolerance is the tolerance of a dose of 4043mg of cashew protein. Primary outcomes include the proportion of participants tolerating a single dose of 4043mg cashew protein during the final oral food challenge. Secondary outcomes assess adverse events, changes in immunological parameters, and the maximum tolerated doses of cashew protein in each group.

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-18
• Study First Submitted QC: 2024-03-22
• Study First Posted: 2024-03-25
• Study Start: 2024-03-28
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-01-30
• Primary Completion: 2026-04-21
• Study Completion: 2027-04-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• age between 4 and 17 years,
• IgE (immunoglobulin E) -mediated cashew allergy confirmed with positive skin prick tests with cashew allergens (diameter of the wheal greater than 3mm) and/or specific IgE (immunoglobulin E) level greater than 0.35-kilo units of Allergen per liter (kUA/l),
• allergic reaction to cashew protein during oral food challenge (OFC),
• Signed Informed Consent by parent/legal guardian and patient aged >16 years old,
• Patient's and caregivers' cooperation with the researcher.

Exclusion Criteria

• no confirmed allergy to cashew,

• negative provocation test with cashew,

• severe asthma,

• mild/moderate asthma poorly controlled: FEV1 (forced expiratory volume at one second) <80% (less than 5 perc), FEV1/FVC (forced expiratory volume at one second/forced vital capacity) <75% (less than 5 perc), hospitalization for asthma exacerbation in the past 12 months,

• oral/sublingual/subcutaneous immunotherapy to other allergens during the study,

• eosinophilic gastroenteritis,

• chronic diseases requiring ongoing treatment, including heart disease, epilepsy, metabolic diseases, diabetes,

• taking medications:

  • oral, daily steroid therapy >1 month in the past 12 months,
  • a minimum of 2 times oral steroid therapy (a period of at least 7 days) in the past 12 months,
  • one-time oral steroid therapy (min. 7 days) in the last 3 months,
  • biological treatment,
  • need to take antihistamines continuously,
  • therapy with β-blockers, ACE-inhibitors (angiotensin converting enzyme), calcium channel inhibitors,

• pregnancy,

• lack of consent to participate in the study,

• lack of patient cooperation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cashew Immunotherapy	Cashew immunotherapy	Children with cashew allergy receiving OIT (OIT-oral immunotherapy).

Primary Outcome Measures

Name	Time	Method
Cashew full tolerance	Up to 60 weeks of OIT (oral immunotherapy)	Percentage of children tolerating a single dose of 4g of cashew protein after 12 weeks of immunotherapy at a maintenance dose.

Secondary Outcome Measures

Name	Time	Method
Basophil activation test (BAT)	Up to 60 weeks of OIT (oral immunotherapy)	Difference in BAT test values between groups before and after 12 weeks of immunotherapy at maintenance dose or after 60 weeks of immunotherapy
Cashew partial tolerance	Up to 60 weeks of OIT (oral immunotherapy)	Percentage of children with partial tolerance, defined as an increase in the tolerated dose by at least 10-fold and tolerance of at least 1.2g of cashew protein but less than 4g of cashew protein at the end of 12 weeks of cashew protein immunotherapy at the maintenance dose or after 60 weeks of immunotherapy
OIT safety	Up to 60 weeks of OIT (oral immunotherapy)	Number and type of side effects during oral desensitization with cashew protein, divided into mild, moderate and severe.
IgG4 (immunoglobulin IgG4) (mgA/l) levels	Up to 60 weeks of OIT (oral immunotherapy)	Difference in sIgG4 (immunoglobulin IgG4) (mgA/l) levels against cashew, walnut, pistachio, peanut, hazelnut and almond allergens evaluated between groups 12 weeks of immunotherapy at maintenance dose or after 60 weeks of immunotherapy.
Wheal diameter in skin prick tests	Up to 60 weeks of OIT (oral immunotherapy)	Difference in wheal diameter in skin prick tests between groups before and after completion of 12 weeks of cashew protein immunotherapy at the maintenance dose or after 60 weeks of immunotherapy.
SIgE (specific immunoglobulin E) (kUA/l) levels	Up to 60 weeks of OIT (oral immunotherapy)	Difference in sIgE (specific immunoglobulin E) (kUA/l) levels against cashew, walnut, pistachio, peanut, hazelnut and almond allergens evaluated between groups 12 weeks of immunotherapy at maintenance dose or after 60 weeks of immunotherapy.
Quality of life- FAQLQ (Food Allergy Quality of Life Questionnaire)	Up to 60 weeks of OIT (oral immunotherapy)	Assessment of quality of life before and after desensitization (impact on families' lives) using FAQLQ. In children up to 12 years old we use FAQLQ-PF (Parent Form) and FAQLQ-CF (Child Form) in children 8-12 years old. For children 13-17 years old we use FAQLQ-TF (Teenager Form).; These questionnaires are under validation in Polish and will be used if validation is completed.; The FAQLQ-PF consists of 30 questions divided into three domains: Emotional Impact, Food Anxiety, and Social and Dietary Restrictions. Parents of children aged 4-6 years old answer 26 questions, and parents of children aged 7-12 years old answer all 30 questions. The FAIM (Food Allergy Independence Measure) consists of four questions and assesses parents expectations of their child's food allergy outcomes.; FAQLQ- CF consist of 30 questions. FAQLQ- TF consist of 28 questions. Every question in all questionaires except FAIM part is assessed in 7 points scale, the higher value the worse outcome.
Air condensate	Up to 60 weeks of OIT (oral immunotherapy)	Evaluation of pro-inflammatory cytokine levels in exhaled air condensate

Trial Locations

Locations (1)

Medical University of Warsaw; 🇵🇱 Warsaw, Mazowieckie, Poland