Peanut and Tree Nut Desensitization

Peanut/Tree Nut Desensitization and Induction of Tolerance in Children

this study evaluates whether tolerance to peanuts and tree nuts can be induced in patients through a process of oral immunotherapy. Participants will be randomized into groups receiving oral immunotherapy and a control group that will receive no intervention

Study Overview

• Status: Active, not recruiting
• Conditions: Peanut Allergy; Tree Nut Allergy
• Intervention / Treatment: Other: Oral immunotherapy

Detailed Description

The investigators are proposing to initiate a study assessing a common desensitization protocol for peanut/tree nut allergy. This study would enable the investigators to better determine the potential benefit of desensitization in individuals with peanut/tree nut allergy.

More specifically, the investigators will address the following research objectives:

Objectives A. To develop a protocols for peanut/tree nut desensitization with high (300mg) and low (30mg maintenance dose).

B. To determine the rate of desensitization to peanut/tree nut. C. To characterize predictors of successful desensitization. D. To characterize molecular mechanisms involved in the process of desensitization

These objectives will be evaluated through a randomized controlled trial

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital For Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Montreal Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 40 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria: Patients between 2 and 40 years of age who satisfy all the following criteria will be included:

• A history suggestive of immediate allergy to peanut/tree nut . A convincing clinical history of an IgE mediated reaction to a specific food will be defined as a minimum of 2 mild signs/symptoms or 1 moderate or 1 severe sign/symptom that was likely IgE mediated and occurred within 120 minutes after ingestion or contact (or inhalation in the case of fish and shellfish). Reactions will be considered mild if they involve pruritus, urticaria, flushing, or rhinoconjunctivitis; moderate if they involve angioedema, throat tightness, gastrointestinal complaints, or breathing difficulties (other than wheeze); and severe if they involve wheeze, cyanosis, or circulatory collapse.(54-57)

• The presence of at least one of the following confirmatory tests:

  • Positive SPT to peanut/tree nut or its proteins (weal diameter 3 mm larger than that of the normal saline control). The allergens used will be commercial extracts of peanut/tree nut (Omega Labs, Toronto, Ontario).
  • Detection of serum specific IgE (>0.35 kU/L) to peanut/tree nut or any of its proteins, measured by fluorescence enzyme immunoassay (Phadia, CAP System, Uppsala, Sweden).
  • Positive oral challenge test to peanut/tree nut. Oral challenges will be performed with raw peanut/tree nut according to the recommendations of the position paper of the European Academy of Allergology and Clinical Immunology (58).
• Informed consent form signed by the parents or legal guardian

Exclusion criteria.

• Patients who are unstable from a respiratory point of view ..
• Patients who present with intercurrent disease at the time of starting desensitization.
• Non-IgE-mediated or non-immunological adverse reactions to nuts.
• Malignant or immunopathological diseases and/or severe primary or secondary immune deficiencies.
• Patients receiving immunosuppressor therapy
• Patients receiving β-blockers (including topical formulations).
• Associated diseases contraindicating the use of epinephrine: cardiovascular disease or severe hypertension.
• Patients diagnosed with eosinophilic gastrointestinal disorder .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; Following randomization, this arm will receive no intervention. After twelve months, participants in this group will undergo a singe-blind, placebo-controlled oral food challenge
ACTIVE_COMPARATOR: Low-dose; Following randomization, participants in this group will receive escalating doses of the appropriate allergen, up to a dose of 30 mg. Once they attain that dose, they will maintain it for six months. At the end of this maintenance period, they will undergo a singe-blind, placebo-controlled oral food challenge	Other: Oral immunotherapy; Starting from a very low level and over a period of several months, participants receive escalating doses of the food to which they are allergic
ACTIVE_COMPARATOR: High-dose; Following randomization, participants in this group will receive escalating doses of the appropriate allergen, up to a dose of 300 mg. Once they attain that dose, they will maintain it for six months. At the end of this maintenance period, they will undergo a singe-blind, placebo-controlled oral food challenge	Other: Oral immunotherapy; Starting from a very low level and over a period of several months, participants receive escalating doses of the food to which they are allergic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of desensitization in peanut/tree nut allergic patients as measured by blinded, placebo controlled oral food challenge	Comparison of participants randomized to treatments arms who achieve peanut/tree nut desensitization compared to participants randomized to the control groups. This is measured by whether a participant is able to tolerate a total dose of 4172 mg crushed peanut or tree nut during an oral food challenge	21 months
Comparison of efficacy of 30 mg dose versus 300 mg dose in inducing desensitization to peanut or tree nut as measured by blinded, placebo controlled oral food challenge	Participants in the 30 mg arm will be compared to those in the 300 mg in terms of dose tolerated at post-immunotherapy blinded, placebo-controlled oral food challenge, as well as side effects experienced during immunotherapy	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline over the immunotherapy process of peanut or tree nut (as appropriate) specigic IgE levels	Measurement of peanut or tree nut (as appropriate) specigic IgE before, during and after the desensitization process	21 months
Change from baseline over the immunotherapy process of peanut or tree nut (as appropriate) specigic IgA levels	Measurement of peanut or tree nut (as appropriate) specigic IgA before, during and after the desensitization process	21 months
Change from baseline over the immunotherapy process of peanut or tree nut (as appropriate) specigic IgG4 levels	Measurement of peanut or tree nut (as appropriate) specigic IgG4 before, during and after the desensitization process	21 months
Change from baseline over the immunotherapy process of mast cell activation as measured by CD63 expression	Measurement of mast cell activation as measured by CD63 expression before, during and after the desensitization process	21 months
Change from baseline over the immunotherapy process of of DNA methylation levels	Measurement of DNA methylation levels before, during and after the desensitization process	21 months
Change from baseline over the immunotherapy process of Regulatory T cell levels	Measurement of Regulatory T cell levels, before, during and after the desensitization process	21 months

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: Julia Upton, Hospital for Sick Children, University of Toronto

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 19, 2018
• Primary Completion (ANTICIPATED): January 2, 2024
• Study Completion (ANTICIPATED): January 2, 2024

Study Registration Dates

• First Submitted: March 16, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (ACTUAL): May 22, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Nut Hypersensitivity
• Other Study ID Numbers: 2017-3204

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No