Tree Nut AllergyReINANCT04151069
Re-Introducing Nuts in Allergic Patients
An observational study of Tree Nut Allergy, run by National and Kapodistrian University of Athens at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 40 years
- Conditions the study is for
- Tree Nut Allergy
- What is being tested?
- Procedure A and Procedure B
- How many people
- 60 participants
- Where
- 1 siteGreece
- Study dates
- 16 Jul 2019to 30 May 2024
- Phase
- Observational
- 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 5 to 40 years
- All sexes
- Child, Adult
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.
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Greece1 site
Department of Allergy and Clinical Immunology, 2nd University Pediatric Clinic of "Panagiotis & Aglaia Kyriakou" Children's Hospital, Athens, Greece
Athens, Attica, 11527
About this study
Official title: Comparison of Protocols for Re-introducing Tree Nuts in Patients With Allergy to Tree Nuts
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.
Read the 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.
- Conditions
- Tree Nut Allergy
- Being tested
- Procedure A, Procedure B, Control group
- Keywords
- Tree Nut Allergy, Walnut Allergy, Pistachio Allergy, Cashew Allergy, Tree Nut Hypersensitivity, Tree Nut Anaphylaxis
- Medical subject headings
- Nut Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procedure AOther
Up-dosing nut drink at home
Procedure BOther
Up-dosing nut drink at the hospital
Control groupOther
Strict avoidance of tree nut consumption
| Study group | Role | What they receive |
|---|---|---|
| At home group | Participants with allergy to tree nuts who follow the introduction procedure A (at home) Receives: Other: Procedure A | |
| At the hospital group | Participants with allergy to tree nuts who follow the introduction procedure B (at the hospital) Receives: Other: Procedure B | |
| Control group | Participants with allergy to tree nuts who follow strict avoidance of the offending nuts. Receives: Other: Control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of allergic reactions in procedure A and procedure B.
Comparison of the frequency and severity of allergic reactions, and the frequency of adrenaline use in two remedies.
Measured: 2 years.
Number of patients who adhere to each procedure (A or B).
Comparison of the proportion of participants who follow the procedure.
Measured: 2 years.
Number of participants with tolerance induction after procedure A and B compared to strict avoidance.
The proportion of participants in each group who achieve to consume 300mg of tree nut protein at Final Assessment (cumulative dose of 433mg ), if baseline provocation dose was ≤100mg, or 1000mg (cumulative dose 1433mg), if baseline provocation dose was ≥300mg.
Measured: 2 years.
Secondary outcomes (3)
Comparison of the mean change in the maximum tolerated dose in participants following procedure A compared to procedure B.
The change in the maximum tolerated dose of the tree nut between baseline and final assessment.
Measured: 2 years.
Immunological alterations induced by the two procedures.
Alterations in SPTs, sIgEs and BAT outcomes between baseline and final assesment.
Measured: 2 years.
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'.
The effect of two procedures in quality of life of patients as measured by FAQLQ-FAIM at baseline, 6 months and final assessment.The Food Allergy Quality of Life Questionnaires (FAQLQ) are disease-specific health-related quality of life (HRQL) questionnaires for patients with food allergy.The number of items of each FAQLQ ranges from 23 to 30 items, depending on age. Each question is answered on a 7-point scale (0 "no impairment" to 6 "maximal impairment" ).
Measured: 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2019
- Study start16 Jul 2019
- Primary completion30 May 2024 (estimated)
- Study completion30 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tree Nut AllergyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Collaborators
- Hellenic Society of Allergology and Clinical Immunology
- Responsible party
- Principal investigator, Maria Pasioti, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04151069
- Sponsor's protocol ID
- 1718037516
- Acronym
- ReINA
- Status last verified
- Apr 2024
- First submitted
- 31 Oct 2019
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Protocols for Re-introducing Tree Nuts in Patients With Allergy to Tree Nuts
- ClinicalTrials.gov ID
- NCT04151069
- Acronym / sponsor ID
- ReINA / 1718037516
- Conditions
- Tree Nut Allergy
- Keywords
- Tree Nut Allergy, Walnut Allergy, Pistachio Allergy, Cashew Allergy, Tree Nut Hypersensitivity, Tree Nut Anaphylaxis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Collaborators
- Hellenic Society of Allergology and Clinical Immunology
- Study start
- 16 Jul 2019 (actual)
- Primary completion
- 30 May 2024 (estimated)
- Study completion
- 30 May 2024 (estimated)
- First posted
- 5 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| At home group | – | Other: Procedure AParticipants with allergy to tree nuts who follow the introduction procedure A (at home) |
| At the hospital group | – | Other: Procedure BParticipants with allergy to tree nuts who follow the introduction procedure B (at the hospital) |
| Control group | – | Other: Control groupParticipants with allergy to tree nuts who follow strict avoidance of the offending nuts. |
Who may qualify
- Ages
- 5 to 40 years
- Sex
- All
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (11 listed)
- 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:
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Procedure AUp-dosing nut drink at home | Other | At home group |
| Procedure BUp-dosing nut drink at the hospital | Other | At the hospital group |
| Control groupStrict avoidance of tree nut consumption | Other | Control group |
Primary outcome
Number and severity of allergic reactions in procedure A and procedure B.
Time frame: 2 years.
Comparison of the frequency and severity of allergic reactions, and the frequency of adrenaline use in two remedies.
Number of patients who adhere to each procedure (A or B).
Time frame: 2 years.
Comparison of the proportion of participants who follow the procedure.
Number of participants with tolerance induction after procedure A and B compared to strict avoidance.
Time frame: 2 years.
The proportion of participants in each group who achieve to consume 300mg of tree nut protein at Final Assessment (cumulative dose of 433mg ), if baseline provocation dose was ≤100mg, or 1000mg (cumulative dose 1433mg), if baseline provocation dose was ≥300mg.
3 secondary outcomes
Comparison of the mean change in the maximum tolerated dose in participants following procedure A compared to procedure B.
Time frame: 2 years.
Immunological alterations induced by the two procedures.
Time frame: 2 years.
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'.
Time frame: 2 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tree Nut Allergy, run by National and Kapodistrian University of Athens at 1 site in Greece.
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 11 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 2 Apr 2024. 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 Greece. 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.
Are results available for this study?
Results are not available in the source record.
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?
Number and severity of allergic reactions in procedure A and procedure B. (time frame: 2 years.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2024; AzTrials last refreshed its copy on 26 Oct 2026.