Clinical trial NCT04151069: Re-Introducing Nuts in Allergic Patients
Official title: Comparison of Protocols for Re-introducing Tree Nuts in Patients With Allergy to Tree Nuts
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Tree Nut Allergy
Keywords: Tree Nut Allergy
Walnut Allergy
Pistachio Allergy
Cashew Allergy
Tree Nut Hypersensitivity
Tree Nut Anaphylaxis
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: Hellenic Society of Allergology and Clinical Immunology
First posted: 2019-11-05
Enrollment: 60
Sex: ALL
Minimum age (years): 5
Maximum age (years): 40
Standard ages: CHILD
ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adults seen in specialized Allergy Departments of three hospitals in Athens with allergy to at least one of the tree nuts studied, namely walnut, cashew and/or pistachio.

Brief summary: This study aims to compare the safety and the compliance to different procedures (A: at home or B: at the hospital) for introducing tree nuts into the diet of patients with Immunoglobulin E (IgE)-mediated allergy to the aforementioned nuts. In parallel, the effectiveness of tree nuts' introduction in respect to tolerance induction compared to the standard care (strict avoidance of tree nuts) will be evaluated.

Detailed description: This is a multi-centered observational study comparing the safety and compliance of different procedures for introducing tree nuts into the diet of patients with IgE-mediated allergy to nuts. The effectiveness of tree nuts' introduction in respect to tolerance induction compared to the standard care (strict avoidance of tree nuts) will also be evaluated.

The study will be contacted in the Department of Allergy and Clinical Immunology, 2nd University Pediatric Clinic of "Panagiotis \& Aglaia Kyriakou" Children's Hospital, Athens, Greece, in collaboration with the Allergy Unit "Dimitrios Kalogeromitros, 2nd University Clinic of Dermatology and Venereology, "Attikon" University Hospital, University of Athens, Greece and the Allergology Department of "Laiko" General Hospital, Athens, Greece.

The study will include participants with persistent IgE mediated allergy to tree nuts (including at least walnut or pistachio) who are willing to follow one of the two induction procedures (A: at home, B: at the hospital) and voluntarily provide written consent in the procedures and the goals of the study. Participants will adhere to one of the two induction procedures according to their preferences. Groups will be matched in respect to the number of participants.

Participants who have already followed one of the two procedures can participate following written informed consent.

The control group consists of participants who do not wish to introduce tree nuts into their diet but will consent to provide their medical data and the results of their allergology work-up for research purposes. The target ratio between active and control groups will be 3:1.

Introduction of Tree Nuts consists of:

Baseline Assessment (Screening period):

In all participants, active and control, IgE-mediated allergy is evaluated by Skin Prick Tests (SPTs), serum specific IgE (sIgE) to tree nuts, serum sIgE to tree nuts' components and Basophile Activation Test (BAT) to the implicated tree nut and is confirmed by oral food challenges (OFC) with the nut. Additionally, total IgE and tryptase levels are assessed.

Tree Nuts' Introduction Phase:

Commercially available drinks of the respective tree nut, in suitable dilutions, are used for the introduction.

First day of introduction: Participants in both active groups (procedures A and B) receive the first dose of the drink in the hospital under specialized medical observation.

Escalation period: Drinks in suitable dilutions are given daily to participants. Dose escalation is performed at weekly intervals at home (procedure A) or every 2 months at the hospital (procedure B) until reaching maintenance dose or patient's maximum tolerated dose. The escalation period is estimated at 64 weeks (16 months). The up-dosing scheme and maintenance dose and duration will be adjusted in case of adverse allergic reactions.

Maintenance Phase: The maintenance starts when participants reach the maintenance dose or their maximum tolerated dose, and lasts for at least 4 weeks.

Participants in the control group are instructed to strictly avoid offending tree nuts, as per standard care.

During Tree Nuts' Introduction Phase all participants, active and control, will be followed up periodically in two months intervals.

Final Assessment:

After completing at least 4 weeks at maintenance phase all participants will undergo an open oral food challenge with the offending nut(s) to assess tolerance. SPTs, total IgE, serum sIgE to tree nuts, serum sIgE to tree nuts' components and Basophile Activation Test (BAT) to each tree nut the participant is allergic will be re-evaluated.

Eligibility criteria: Inclusion Criteria:

* Written informed consent from adult participants or parent/guardian for children. Written assent from participants above the age of 12 years.
* Male or female participants aged 5 through 40 years, in a good general health condition according to the participant's medical history and the clinical examination and no chronic diseases, except:

  * Allergic rhinitis
  * Asthma controlled with therapy steps 1-3 according to Global Initiative for Asthma (GINA) 2017.
  * Well-controlled atopic dermatitis.
* SPT to tree nut's extract and/or the natural tree nut (Prick-to-Prick) ≥ 3 mm (the largest diameter of the wheal) and serum IgE to tree nut of ≥ 0.35 kUA/L.
* sIgE \> 0.1 kUA/L to at least one seed storage protein of the offending tree nut, except for pistachio, where Ana o 3 will serve as a sensitization marker.
* Positive baseline OFC, at any dose but the final, conducted following PRACTALL (Practical Issues in Allergology, Joint United States/European Union Initiative) / iFAAM (Integrated Approaches to Food Allergen and Allergy Risk Management) guidelines.
* Exclusion of active co-allergy to walnut, almond or pistachio, unless they are introduced to the diet simultaneously, by a negative open OFC or a recent (within the last two months) history of uneventful digestion, except for pistachio introduction in participants who are co-allergic to cashew.
* Forced Expiratory Volume at 1 second (FEV1) or Peak Expiratory Flow Rate (PEFR) ≥ 80% of predictive.
* The participant and/or the legal custodian should agree to comply with the study procedures.

Exclusion Criteria:

* History of systematic anaphylaxis GRADE 5 according to Sampson (loss of bowel control, respiratory arrest, severe bradycardia and/or hypotension or cardiac arrest, loss of consciousness) or/and during OFC.
* Recent (within 12 months) initiation of immunotherapy to any allergen.
* Past or present eosinophilic esophagitis (EoE).
* Chronic urticaria.
* Severe or uncontrolled atopic dermatitis.
* Uncontrolled asthma of any severity or asthma controlled with therapy steps 4-5 according to GINA 2017.
* Concurrent or within 6 months therapy with omalizumab or another monoclonal antibody.
* Systematically used corticosteroids:

  * Daily for more than a month during the last year,
  * Courses of corticosteroids during the last 3 months.
  * \>2 Courses of corticosteroids lasting ≥1 week during the last year.
* Inability to discontinue antihistamines 4 days before skin prick testing or OFC.
* Severe immune disease, severe cardiovascular disease, malignancy, chronic infection, poor compliance, and severe psychiatric disorders.
* Any important clinical condition that can affect the safety of the participant or the results of the study, including but not limited to cardiovascular diseases, malignancies, diseases of the liver and/or the kidneys, hematologic diseases, physiologic, immunologic and endocrinologic diseases.
* Use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARB).
* Pregnancy or lactation.
* History of alcohol or drug abuse.

Primary outcomes:
measure: Number and severity of allergic reactions in procedure A and procedure B.
timeFrame: 2 years.
measure: Number of patients who adhere to each procedure (A or B).
timeFrame: 2 years.
measure: Number of participants with tolerance induction after procedure A and B compared to strict avoidance.
timeFrame: 2 years.
Secondary outcomes:
measure: Comparison of the mean change in the maximum tolerated dose in participants following procedure A compared to procedure B.
timeFrame: 2 years.
measure: Immunological alterations induced by the two procedures.
timeFrame: 2 years.
measure: Mean change from baseline in Food Allergy Quality of Life Questionnaire- Food Allergy Independent Measure (FAQLQ-FAIM)-Likert scale-questions , range from 1 'not troubled' to 7 'extremely troubled'.
timeFrame: 2 years.
Other outcomes:
measure: Mean change from baseline in specific Immunoglobulin G (IgG) and Immunoglobulin G4 (IgG4) serum levels.
timeFrame: 2 years
measure: Epigenetic and transcriptomic changes related to tolerance induction.
timeFrame: 2 years
measure: Changes in the gut microbiome of participants.
timeFrame: 2 years
Locations:
city: Athens
country: Greece
facility: Department of Allergy and Clinical Immunology, 2nd University Pediatric Clinic of "Panagiotis & Aglaia Kyriakou" Children's Hospital, Athens, Greece
state: Attica
Study officials:
References: