Immunotherapy for Tree Nut Allergy
(TRADE Trial)
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Hamilton Health Sciences Corporation
Must not be taking: Biologics, Antihistamines, others
Disqualifiers: Anaphylaxis, Asthma, Pregnancy, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Tree nut immunotherapy Route Assessment and DEvelopment (TRADE) is a randomized controlled trial that evaluates the efficacy and safety of sublingual immunotherapy and lower, more tolerable, doses of oral immunotherapy than currently in use.
Do I need to stop my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but you must stop taking antihistamines for 7 days before assessment visits.
What data supports the effectiveness of the treatment Tree Nut Immunotherapy for tree nut allergies?
Research shows that oral immunotherapy (OIT) is effective for desensitizing people with food allergies like peanut, egg, and milk, suggesting it might also work for tree nut allergies. Additionally, sublingual immunotherapy (SLIT) has been effective for other allergies, like birch and grass pollen, indicating potential for tree nut allergy treatment.
12345Is tree nut immunotherapy safe for humans?
Tree nut immunotherapy, including oral and sublingual methods, generally shows a good safety profile with most side effects being mild and local, such as irritation at the site of administration. Serious reactions are rare, and no fatalities have been reported in studies, but systemic reactions like urticaria (hives) and asthma can occur, especially with oral immunotherapy.
16789How is Tree Nut Immunotherapy different from other treatments for tree nut allergies?
Tree Nut Immunotherapy is unique because it aims to desensitize individuals to tree nuts through oral or sublingual administration, potentially allowing them to tolerate nuts they are allergic to, unlike the current standard of strict avoidance. This approach is similar to immunotherapies used for other food allergies like peanuts, but it is still in the exploratory phase for tree nuts due to the complexity of multiple nut allergies and lack of standardized products.
14101112Eligibility Criteria
The TRADE Trial is for individuals who are allergic to tree nuts and react to 444 mg of nut protein or less. Participants must consent to the trial, and if they're minors, they need parental consent as well.Inclusion Criteria
Allergic to tree nut with baseline threshold of 444 mg protein or less and provides consent, and where applicable, assent.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sublingual immunotherapy and/or low dose oral immunotherapy
1 year
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Participant Groups
This study tests two ways of treating tree nut allergies: sublingual immunotherapy (medicine placed under the tongue) and oral immunotherapy with lower doses than currently used. It's a randomized controlled trial, meaning participants are randomly assigned to different treatment groups.
3Treatment groups
Experimental Treatment
Group I: Placebo low dose oral immunotherapy and Placebo sublingual immunotherapyExperimental Treatment1 Intervention
Group II: Placebo low dose oral immunotherapy and Active sublingual immunotherapyExperimental Treatment1 Intervention
Group III: Active low dose oral immunotherapy and Placebo sublingual immunotherapyExperimental Treatment1 Intervention
Tree Nut Immunotherapy is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Tree Nut Immunotherapy for:
- Tree nut allergy
🇨🇦 Approved in Canada as Tree Nut Immunotherapy for:
- Tree nut allergy
🇪🇺 Approved in European Union as Tree Nut Immunotherapy for:
- Tree nut allergy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
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Who Is Running the Clinical Trial?
Hamilton Health Sciences CorporationLead Sponsor
AAAAI FoundationCollaborator
References
Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. [2020]The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts.
Clinical and immunological correlates of pre-co-seasonal sublingual immunotherapy with birch monomeric allergoid in patients with allergic rhinoconjunctivitis. [2019]Sublingual immunotherapy is safe and efficacious in the treatment of patients with allergic rhinitis. The clinical and biological efficacy of modified allergens (allergoids) has not been fully clarified. We investigated in birch allergic patients the effect of a pre-co-seasonal sublingual immunotherapy regimen with a modified allergen extract on clinical parameters and on T cell proliferation and regulatory cytokine production (IL-10, TGF-beta). We found that during the birch pollen season symptoms and drug usage scores were 30 and 40 percent improved, respectively, in treated versus control subjects (p
Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy. [2019]Sublingual immunotherapy (SLIT) with peanut changes clinical and immune responses in most peanut-allergic individuals, but the response is highly variable.
Irradiated Tree Nut Flours for Use in Oral Immunotherapy. [2021]Tree nut allergies affect an estimated 1% of the US population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products.
Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract. [2011]Sublingual immunotherapy (SLIT) with a high-dose 6-grass pollen SingleDose preparation was shown to be effective and safe in a 2-year randomized, double-blind, placebo-controlled trial.
[New administration routes for immunotherapy]. [2007]Specific immunotherapy represents the turning point of the treatment of allergic illnesses and this, together with avoiding the allergen, currently constitutes the only etiologic treatment available. When conditions are optimum, which include showing the etiologic importance of the allergen, the availability of quality allergenic extracts and the correct monitoring of the patient, immunotherapy with subcutaneous injections is a safe and efficient treatment. As in any other treatment, subcutaneous immunotherapy is not exempt from possible adverse reactions related to its administration, although when the recommended guidelines are followed, these reactions tend to be predominantly local, of little intensity and easy to control. Over the last 15 years, especially in Europe, there has been an increased interest in the use of local applications, not injections, in immunotherapy and we are looking, above all, to increase the safety and the patients acceptance. The alternative applications to injected immunotherapy that have been studied and used to date are: oral, sublingual, nasal and bronchial. In the World Health Organisation position papers (WHO), from the European Academy of Allergies and Clinical Immunology (EAACI) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI), bronchial immunotherapy is not recommended, due to the fact that its efficiency is not sufficiently documented and the there is a risk involved with severe side effects of an asthmatic nature. Nasal immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not recommended, except as part of controlled studies, due to the risk of side effects and insufficient documentation that guarantees the efficiency. Currently, in clinical practice, it apears that a progressive interest has been detected in sublingual immunotherapy and in our country this is being used more and more, which means that the current level of our knowledge on this terapeutical method should be reviewed. In order to consider sublingual immunotherapy as a valid alternative, taking the bassis of its action mechanisms as a starting point, a greater safety in its administration should be checked, its clinical efficiency demonstrated and this efficiency should at least be comparable to that obtained using subcutaneous immunotherapy. The action mechanism of sublingual immunotherapy is unknown. Experiments using allergenic extracts marked with radioactive isotopes administered sublingually do not indicate any absorption through the oral mucous, which is reassuring in the sense that no systematic adverse reactions are feared, but on the other hand we are faced with serious doubts concerning the basis for this type of immunotherapy administration. Sublingual immunotherapy, especially when the treatment is exclusively sublingual (where the dose is subsequently spat out), is a safe treatment according to what can be deduced from the clinical tests and the pharmacovigilance studies published, although the sublingual means of administration with a subsequent ingestion of the dose can give rise to adverse systematic reactions, such as urticaria and asthma. From the experience gained since this method has been used, to date there have been no reported serious systematic reactions that are life threatening. The analysis of the results of the double-blind control clinical tests published to date, lead us to the same conclusion as the WHO, the EAACI and the ESPACI position papers, in the sense that there is not sufficient evidence available to recommend the use of sublingual immunotherapy on children, except when it is part of a controlled study. (ABSTRACT TRUNCATED)
Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients. [2019]Immunotherapy (IT) is the only causal treatment for allergic subjects recognized to be effective and to offer long-lasting efficacy. The noninjective routes, aimed at improving the safety of the treatment, have been validated as effective in adults, but documentation of their safety in children is still poor. The aim of the present survey study was to assess the safety of sublingual immunotherapy in pediatric patients, by evaluating a large population.
Local Side Effects of Sublingual and Oral Immunotherapy. [2022]Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT.
Safety of sublingual grass pollen immunotherapy after anaphylaxis. [2009]To demonstrate that sublingual immunotherapy is a safe treatment option in patients who have previously suffered anaphylaxis when undergoing subcutaneous grass pollen immunotherapy.
New modalities of allergen immunotherapy. [2023]Allergen immunotherapy is a rapidly evolving field. Although subcutaneous immunotherapy has been practiced for over a hundred years, improved understanding of the underlying immunological mechanisms has led to the development of new, efficacious and better tolerated allergen-derivatives, adjuvants and encapsulated allergens. Diverse routes of allergen immunotherapy - oral, sublingual, epicutanoeus and intralymphatic - are enabling immunotherapy for anaphylactic food allergies and pollen-food allergy syndrome, while improving the tolerability and effectiveness of aeroallergen immunotherapy. The addition of Anti-IgE therapy decreases adverse effects of subcutaneous and oral immunotherapy.
Tree nut allergies: Allergen homology, cross-reactivity, and implications for therapy. [2023]Tree nut allergy is a potentially life-threatening disease that is increasing in prevalence, now affecting 1% of the general population in the United States. While other food allergies often resolve spontaneously, tree nut allergies are outgrown in less than 10% of cases. Due to the likelihood of cross-sensitization to multiple tree nut allergens, the current treatment guideline is strict avoidance of all nuts once one tree nut allergy has been diagnosed. For example, walnut and pecan are highly cross-reactive, along with cashew and pistachio, but the extent of clinical, IgE-mediated cross-reactivity among other tree nuts remains unclear, therefore making avoidance of all tree nuts a safe approach. There have been recent advances in immunotherapy for food allergies. For instance, there are investigational immunotherapies for milk, egg and peanut allergies, specifically oral immunotherapy, sublingual immunotherapy and epicutaneous immunotherapy. However, there are no large randomized controlled clinical trials for tree nut allergies. Even though there has been less research into tree nut allergy immunotherapies, the evidence of T-cell cross-reactivity among tree nuts exists in animal models and in T cells from allergic patients indicates that immunotherapeutic interventions may be possible. Here, we review the literature regarding epidemiology, allergen homology and cross-reactivity among tree nuts, and explore how current findings can be employed for effective therapy.
Differences and similarities between sublingual immunotherapy of allergy and oral tolerance. [2018]Allergen immunotherapy is the only treatment altering the natural course of IgE-mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has been historically considered as a reference, we discuss herein the relative advantages of the sublingual and oral routes as alternatives to SCIT in order to elicit allergen-specific tolerance. The buccal and gut immune systems are similarly organized to favor immune tolerance to antigens/allergens, due to the presence of tolerogenic dendritic cells and macrophages promoting the differentiation of CD4+ regulatory T cells. Sublingual immunotherapy (SLIT) is now established as a valid treatment option, with clinical efficacy demonstrated in allergic rhinoconjunctivitis (to either grass, tree, weed pollens or mite allergens) and encouraging results obtained in the management of mild/moderate allergic asthma. While still exploratory, oral immunotherapy (OIT) has shown promising results in the desensitization of patients with food allergies. We review at both biological and clinical levels the perspectives currently pursued for those two mucosal routes.