Investigating Modified Protocols of Oral Immunotherapy to Validate Efficacy and Safety (IMPROVES)

Protocols for Oral Immunotherapy (OIT) for the main food allergens have been recently incorporated in clinical practice for food allergies and their clinical benefits have been acknowledged in European and Canadian official guidelines. There has been some reluctance in both clinicians and patients to implement these therapies, primarily because of the risk of allergic reactions during the desensitization process. This study will investigate if protocols using low doses of a food allergen or processed versions of the allergen can be both effective in conferring desensitization while inducing fewer allergic symptoms during the desensitization process.

Study Overview

• Status: Recruiting
• Conditions: Egg Allergy; Peanut Allergy; Milk Allergy, Cow's
• Intervention / Treatment: Other: Food allergy desensitization / Oral Immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Duncan Lejtenyi, M.Sc; Phone Number: 22369 1-514-934-1934; Email: duncan.lejtenyi@muhc.mcgill.ca
• Study Contact Backup: Name: Liane Beaudette, RN; Phone Number: 68264 1-514-934-1934; Email: liane.beaudette@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Research Institute of the McGill University Health Centre
      • Contact: Duncan Lejtenyi, MSc; Phone Number: 22369 514-934-1934; Email: duncan.lejtenyi@muhc.mcgill.ca
      • Contact: Liane Beaudette; Phone Number: 68264 514-934-1934; Email: liane.beaudette@muhc.mcgill.ca
      • Principal Investigator: Moshe Ben-Shoshan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A history suggestive of immediate allergy to the food. 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

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

  • Positive SPT to the culprit food allergen (weal diameter 3 mm larger than that of the normal saline control). The allergens used will be commercial extracts of the foods (Omega Labs, Toronto, Ontario).
  • Detection of serum specific IgE (>0.35 kU/L) to the culprit food or any of its proteins, measured by fluorescence enzyme immunoassay (Phadia, CAP System, Uppsala, Sweden).

Exclusion Criteria:

• Patients who have uncontrolled respiratory disease (asthma, cystic fibrosis, etc.)
• Patients who present with intercurrent disease active at the time of starting desensitization.
• Non IgE mediated or non-immunological adverse reactions to milk or peanuts.
• Malignant or immunopathological diseases and/or severe primary or secondary immune deficiencies.
• Patients receiving oral immunosuppressor therapy.
• Patients receiving β-blockers (including topical formulations), or who receive daily doses of NSAIDs, aspirin or ACE inhibitors for cardiac issues.
• Associated diseases contraindicating the use of epinephrine: cardiovascular disease, severe hypertension or hypotension.
• Patients diagnosed with eosinophilic gastrointestinal disorders, including patients with a history of antacid use for reflux related to food impaction or with a history of esophageal spasm.
• Patients already tolerating processed/cooked forms of the food (e.g.,baked goods with milk).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Protocol - High Dose Arm; Subjects will progress through desensitization to a high maintenance dose - 1200 mg of crushed peanut, 200 ml of milk or 1200 mg of egg powder.	Other: Food allergy desensitization / Oral Immunotherapy; Participants consume increasing doses of allergenic food daily until they reach a maintenance dose. In the case of the High Dose Arm, participants will progress to a daily dose of either 1200 mg, 300 mg or 200 ml of egg, peanut or milk respectively. Participants randomized to the Low Dose Arm also begin by consuming small amounts of the allergenic food, gradually increasing the daily dose. However, participants in this group only progress to 300 ml, 30 mg or 50 ml daily dose of egg, peanut or milk respectively. The Cooked/Transformed Allergen Arm begins the desensitization with a cooked or transformed form of the allergen - muffins in the case of egg or milk, Bamba puffs in the case of peanut. Participants take increasing amounts of these products (one muffin for egg and milk and four Bamba puffs for peanut) then transition to egg, milk or peanut. Participants then continue their dose progression, getting to 1200 mg, 200 ml or 300 mg for egg, milk and peanut respectively.
Experimental: Modified Protocol - Low Dose Arm; Subjects will progress through desensitization to a low maintenance dose - 120 mg of crushed peanut, 50 ml of milk or 300 mg of egg powder.	Other: Food allergy desensitization / Oral Immunotherapy; Participants consume increasing doses of allergenic food daily until they reach a maintenance dose. In the case of the High Dose Arm, participants will progress to a daily dose of either 1200 mg, 300 mg or 200 ml of egg, peanut or milk respectively. Participants randomized to the Low Dose Arm also begin by consuming small amounts of the allergenic food, gradually increasing the daily dose. However, participants in this group only progress to 300 ml, 30 mg or 50 ml daily dose of egg, peanut or milk respectively. The Cooked/Transformed Allergen Arm begins the desensitization with a cooked or transformed form of the allergen - muffins in the case of egg or milk, Bamba puffs in the case of peanut. Participants take increasing amounts of these products (one muffin for egg and milk and four Bamba puffs for peanut) then transition to egg, milk or peanut. Participants then continue their dose progression, getting to 1200 mg, 200 ml or 300 mg for egg, milk and peanut respectively.
Experimental: Modified Protocol - Cooked/Transformed Allergen Arm; Subjects will begin desensitization with cooked versions of the allergen (muffins in the case of egg and milk) or transformed versions (Bamba puffs for peanut). They will progress up to a full muffin or 4 Bamba puffs (for egg/milk and peanut respectively). Once subjects have reached these doses, they will transition to doses of pure allergen. They will then progress to the same top dose as subjects in the High Dose Arm.	Other: Food allergy desensitization / Oral Immunotherapy; Participants consume increasing doses of allergenic food daily until they reach a maintenance dose. In the case of the High Dose Arm, participants will progress to a daily dose of either 1200 mg, 300 mg or 200 ml of egg, peanut or milk respectively. Participants randomized to the Low Dose Arm also begin by consuming small amounts of the allergenic food, gradually increasing the daily dose. However, participants in this group only progress to 300 ml, 30 mg or 50 ml daily dose of egg, peanut or milk respectively. The Cooked/Transformed Allergen Arm begins the desensitization with a cooked or transformed form of the allergen - muffins in the case of egg or milk, Bamba puffs in the case of peanut. Participants take increasing amounts of these products (one muffin for egg and milk and four Bamba puffs for peanut) then transition to egg, milk or peanut. Participants then continue their dose progression, getting to 1200 mg, 200 ml or 300 mg for egg, milk and peanut respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of anaphylaxis in different Oral Immunotherapy protocols	Do participants in the different study arms experience similar rates of anaphylaxis during their participation in the study? Anaphylaxis is defined as an allergic reaction to the food the subject is allergic to, that involves symptoms in two of the following organ systems: skin, respitratory, gastro-enterologic or neurologic.The Consortium for Food Allergy Research (CoFAR) grading scale will be used for assessing severuty of allergic symptoms	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of different Oral Immunotherapy protocols	Do participants in the three study arms experience similar levels of desensitization to their allergen? This will be assessed by a Double-Blind Placebo Controlled Oral Food Challenge (DBPCFC). Doses of allergen that elicit symptoms strong enough to end the challenge will be compared between the three groups. Symptom severity will be graded using the CoFAR grading scale.	3 years

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: The Hospital for Sick Children
• Investigators: Principal Investigator: Moshe Ben-Shoshan, MD, MUHC-RI

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 13, 2024

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Milk Hypersensitivity; Egg Hypersensitivity; Peanut Hypersensitivity; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: 2022-8424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared. All participant data will remain strictly confidential

Drug and device information, study documents

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