Low Dose Multi-OIT for Food Allergy (LoMo) (LoMO)

Low Dose Multi Allergen Oral Immunotherapy for Food Allergy

Oral immunotherapy (OIT) is a food allergy treatment where small amounts of the food a child is allergic to is eaten and gradually increased over time with the aim to be able to eat a certain amount of the allergen without experiencing an allergic reaction. While this process works in many children there are concerns about safety, feasibility and drop-outs and how to adapt protocols for multiple allergies.

Many OIT trials have targeted approximately 4000mg of single food/day. In these trials up to 40% drop-out. There is evidence much lower doses can have beneficial effects.

The investigators will evaluate if low doses of foods can allow for OIT to multiple foods. This approach may have efficacy against accidental exposure and be able to demonstrate immune changes. This approach may have a low burden of treatment and a low rate of allergic reactions and

Study Overview

• Status: Active, not recruiting
• Conditions: Food Allergy
• Intervention / Treatment: Other: multi-OIT

Detailed Description

This is a single-arm, open label, study of the intervention of low dose multiple-nut OIT in nut allergic children.

After meeting eligibility criteria, participants will have a food challenge to 2-5 nuts.

If the oral food challenge is positive, participants will be enrolled in the study to multiple nut OIT. A blood draw and quality of life (QOL) survey will occur at baseline.

Participants will have dose escalation visits of the multiple nut OIT every 2 months to a target dose of 30mg of each nut protein. A blood draw and QOL survey will occur at 6 months.

Participants will then continue with daily ingestion of the 30mg of each nut protein for 1 year with visits every 3 months.

After 18 months from the start of the study, another oral food challenge will be given to participants to assess the change in the maximum tolerated dose of nuts. A blood draw will assess changes in the immune parameters. A QOL survey will occur at 18 months to assess changes in QOL.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relevant allergy to 2-5 nuts
• Serum immunoglobulin E (IgE) >0.35 kilounits/L (kU/L) (determined by UniCAP within the past 12 months) and/or a SPT to nut >3 mm compared to control
• Positive oral food challenge (OFC) to less than 300mg of a nut in the nut mix at baseline (cumulative 444mg).

Exclusion Criteria:

• History of frequent or repeated, severe or life-threatening episodes of anaphylactic shock
• use of omalizumab or other non-traditional forms of allergen immunomodulatory therapy (not including corticosteroids) or biologic therapy in the 12 months prior to study entry
• history of eosinophilic gastrointestinal disease, uncontrolled asthma as defined by Global Initiative for Asthma (GINA)
• use of beta-blockers(oral)
• use of angiotensin-converting enzyme inhibitors (ACE)
• fails to tolerate 4mg of peanut after the first desensitization day
• Other significant medical conditions that in the opinion of the investigator prevent participation in the study,
• Previous intubation due to allergies or asthma,
• Symptomatic atopic dermatitis or chronic urticaria which may interfere with ability to evaluate oral immunotherapy and /or requiring daily medication including antihistamines,
• Patients with problems related to compliance or following study instructions, Inability to come to hospital every for dose escalation
• Pregnancy
• Non-fluency in English because participants may need to communicate with us after hours and be able to describe symptoms and concerns and follow instructions to treat anaphylaxis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: multi-OIT; Low dose OIT with multiple allergens	Other: multi-OIT; low dose OIT to multiple foods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desensitization to allergic food as assessed by change in maximum tolerated dose in a dichotomous manner	Change in how much nuts the participant can eat without an allergic reaction after the low dose OIT assessed as dichotomous did the participant reach 5 times the baseline eliciting dose	month 0, month 18
Immunological change in IgG4	Change in allergen specific immunoglobulin G4 (IgG4) from baseline to end	month 0, month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Desensitization to allergic food as assessed by change in maximum tolerated dose on a linear scale	A continuous variable amount tolerated at baseline vs at end	month 0, month 18
Immunological change in IgG4	Change in IgG4 from measures from historical data to 18 month of study. Some patients will have historical IgG4 values to compare	pre-study, month 18
Desensitization to allergic food as assessed by maximum tolerated dose	Did they reach 300mg (cumulative) on the 18 month exit oral food challenge	month 18
Desensitization to allergic food as assessed by maximum tolerated dose	Did they reach 140mg (cumulative) on the 18 month exit oral food challenge	month 0, month 18

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility analysis as assessed by can the patients achieve the maintenance dosing of the allergen mix for OIT	Proportion who achieve maintenance doses of their allergen mix (descriptive)	month 18
Feasibility analysis as assessed by drop-out rate	Proportion who drop-out of the study (descriptive)	month 18
Incidence of Treatment-Emergent Adverse Events: Safety analysis as assessed by use of epinephrine	Administration of epinephrine; (descriptive);	month 18
Quality of life scale	Change in quality of life at 18m of children compared to baseline assessment (using validated questionnaire: Food allergy quality of life questionnaires (FAQLQ) FAQLQ Parental form (PF) for ages 0-12 OR the FAQLQ-teenager form (TF) using total score. The FAQLQ total and domain scores range from 1-7 with higher scores indicative of worse health related quality of life with the total score being the average of the domain scores. The domains include Emotional Impact, Social and Dietary Restrictions, Food Anxiety, Allergen Avoidance, and Risk of Accidental Exposure.	month 0, month 18
Change in allergen specific IgE, and components	Change in allergen specific IgE, and components via microarray	month 0, month 18
Basophil activation test	Basophil activation test	month 0, month 18
Skin prick test (SPT) reactivity to the individual nut extracts	The size of the skin prick test will be compared	month 0, month 18
High content functional immune profiling via mass cytometry and single cell sorting	Compare the change in the immune pattern	pre-study, month 18
Number of participants with treatment related adverse effects	Diaries will be analyzed for allergic symptoms and tabulated	month 0, month 18

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Julia Upton, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2019
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: 1000060633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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