Randomized Controlled Trial of Slow Multiallergen Oral Immunotherapy in Young Children (InFO)

Infant Food Allergen Oral Immunotherapy (InFO)

The aim is to study whether a multiallergen oral immunotherapy (OIT) strategy with slow up-dosing and low treatment dose against food allergy in young children (0.5-3 years) is safe and effective, a method to cure food allergy and to prevent the development of new food allergies.

Clinical randomized controlled (1:1) blinded interventional trial (RCT) with 2 intervention arms (group A and B).

Among 80 children reacting at the multiallergen food challenge, 40 children will be randomized to receive OIT (oral immunotherapy) with multiallergen powder with a final dose of approximately 200 mg protein of each included food (egg, milk, soy, wheat, walnut, peanut, hazelnut, cashew, almond, lentils)(group A) or to receive placebo powder (gluten-free oatmeal) (group B).

A sub-analysis will be performed of the children not reacting to the baseline challenge, who will be randomized to eat a low dose of the multiallergen powder (group C) or placebo powder (gluten-free oatmeal) (group D) and no specific advice.

Study Overview

• Status: Recruiting
• Conditions: Food Allergy; Oral Immunotherapy for Food Allergy
• Intervention / Treatment: Dietary supplement: Multiallergen powder

Detailed Description

Today, there is no established curative treatment for food allergies, and those affected must avoid the food that triggers symptoms. The most studied method is oral immunotherapy (OIT) which have mainly been carried out on children >4 years of age. The OIT method implies that the allergic individual eats initially very low doses and gradually increasing amounts of the allergen until a maintenance dose is reached. The treatment aims to induce desensitization or tolerance to the allergen.

Intervention: The intervention substance is a powder containing a prespecified amount of 10 allergens (egg, milk, wheat, lentils, soy, walnut, peanut, hazelnut, cashew, almond), which are the most triggering allergens in children. The product is developed in cooperation with Research Institute of Sweden (RISE).

Clinical randomized controlled (1:1) blinded interventional trial (RCT) with 2 interventions arms (group A and B). A sub-analysis will be performed of the children not reacting to the baseline challenge (group C and D).

Group A: Children with food allergy (sensitization and positive baseline challenge), receiving multiallergen powder OIT, slow up-dosing until 3 teaspoons of the multiallergen powder is reached daily. Food challenge will be performed after 1 and 2 years. 2 years treatment.

Group B: Children with food allergy (sensitization and positive baseline challenge), receiving OIT with placebo (gluten-free oatmeal) followed by maintenance, in total 2 years. Food challenge will be performed after 1 and 2 years.

Group C and D: sensitized children with a negative baseline challenge will be randomized 1:1 for treatment with multiallergen powder or placebo powder in a lower amount, 1 teaspoon daily and can introduce food in accordance with Swedish guidelines. After one year a food challenge will be performed.

Selection for group A to D: All children 0.5-3 years of age in Stockholm County who had a positive blood test for suspected food allergy to one or more of the 10 included allergens with specific immunoglobulin E (IgE) >0.1 kUA/L, are eligible as possible study participants. The data is obtained from the Karolinska University Laboratory's test results register. Information letters will be sent to families with IgE-sensitized children.

Inclusion groups A to D: Children 0.5-3 years old at inclusion with positive IgE >0.1 kUA/L against at least one of the 10 above mentioned allergens. Eighty children, group A (n=40) and group B (n=40) also need a positive baseline food challenge.

Children with a negative food challenge (group C and D) (number is not determined) do not react at the baseline challenge.

Primary outcome: Tolerance to 900 mg protein, cumulative dose, of each of the 10 included allergens, at the food challenge after two years OIT treatment or placebo (group A and B).

Secondary outcomes: Tolerance to cumulative dose of 900 mg protein of each food, evaluated with a food challenge after one years in all children (group A-D). Changes in immunological markers, eczema and asthma status and changes in quality of life in relation to interventions.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Idun Holmdahl, MD, PhD; Phone Number: +46703002279; Email: idun.holmdahl@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, 11883
    • Recruiting
    • Sodersjukhuset
    • Contact: Idun Holmdahl, MD, PhD; Phone Number: 00460812364037; Email: idun.holmdahl@ki.se

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 0.5-3 years old at inclusion with IgE (>0.1 kUA/l) against at least one allergen (wheat, lentils, egg, milk, soy, walnut, hazelnut, peanut, almond, cashew).
• Written consent for participation in the study for both guardians.
• 80 children (group A and B) also need a positive baseline food challenge.
• Children with a negative food challenge (group C and D) (number not determined) do not react at the baseline challenge.

Exclusion Criteria:

• other serious illness
• previous life-threatening anaphylaxis (intensive care)
• eosinophilic esophagitis
• eosinophilic gastrointestinal disease
• severe chronic gastroesophageal reflux disease
• unclear recurrent GI complaints
• low body weight <2SD
• participation in another intervention study if included in intervention group
• severe uncontrolled asthma
• medication with biological drugs or oral steroids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Allergic children - Multiallergen OIT; Children with food allergy receiving multiallergen powder OIT. Multiallergen food challenge is done before randomization and one and two years after inclusion. OIT multiallergen powder with slow up-dosing until 3 teaspoons of the multiallergen powder is reached and taken daily. 2 years treatment. Number = 40 patients Intervention: multiallergen powder	Dietary supplement: Multiallergen powder; OIT multiallergen powder.
No Intervention: Group B: Allergic children - Placebo powder; Children with food allergy receiving OIT with placebo powder (gluten-free oatmeal). Multiallergen food challenge is done before randomization and one and two years after inclusion. Number = 40 patients
Active Comparator: Group C: Non-allergic children - low dose multiallergen powder; Children not reacting to the baseline challenge who will be randomized to eat a low dose of the multiallergen powder, 1 teaspoon daily. Multiallergen food challenge is done before randomization and one year after inclusion. 1 year treatment. Number = X Intervention: Multiallergen powder	Dietary supplement: Multiallergen powder; OIT multiallergen powder.
No Intervention: Group D: Non-allergic children - placebo powder; Children not reacting to the baseline challenge who will be randomized to eat placebo powder (gluten-free oatmeal) and no specific advice. Number= X

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance to 900 mg protein at a food challenge after 2 years	Tolerance to 900 mg protein, cumulative dose, of each of the 10 included allergens (in the multiallergen powder), evaluated at a food challenge after 2 years in group A and B. Tolerance is defined as no objective sign of an allergic symptom (urticaria, flush, swelling/angioedema, nasal symptoms, eye symptoms, hoarseness, muffled speech, persistent cough, wheezing, stridor, persistent abdominal pain, severe nausea, vomiting, diarrhea, general impact, drop in blood pressure, decreased oxygenation saturation) within 2 hours after the last dose during the food challenge after 2 years of OIT/placebo.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerance to cumulative dose of 900 mg protein at a food challenge after 1 year	Tolerance to cumulative dose of 900 mg protein of each of the 10 included allergens in the multiallergen powder, evaluated at a food challenge after one year in all children (A, B, C, D). Tolerance is defined as no objective sign of an allergic symptom (urticaria, flush, swelling/angioedema, nasal symptoms, eye symptoms, hoarseness, muffled speech, persistent cough, wheezing, stridor, persistent abdominal pain, severe nausea, vomiting, diarrhea, general impact, drop in blood pressure, decreased oxygenation saturation) within 2 hours after the last dose during the food challenge after one year.	1 year
Oral brush samples	The oral microbiome will be investigated with sequencing-based methods to monitor possible changes in the oral microbiota composition and function related to OIT treatment. Comparisons will be made between intervention groups and analyzed in relation to intervention. Oral brush samples will be collected in connection with the visit for the baseline challenge, at the challenge at 1 years (group A-D) and 2 years (group A-B).	1 and 2 years
Intestinal microbiome	The gut microbiome will be investigated with sequencing-based methods to monitor possible changes in the gut microbiota composition and function related to OIT treatment. Comparisons will be made between intervention groups and analyzed in relation to intervention. Fecal samples will be collected in connection with the visit for the baseline challenge, at the challenge at 1 years (group A-D) and 2 years (group A-B).	1 and 2 years
Immunological biomarkers	To study different immunological biomarkers (e.g. T-helper cell population and polarization and IgE-levels) before, during and after OIT treatment and compare this to the placebo group. Immunological marker in mononuclear cells in peripheral blood will be analyzed ex vivo with flowcytometri and RNA-sequencing platforms. Circulating immunological factors, e.g. cytokines and chemokines will be analyzed in plasma with ELISA-based methods. Mononuclear cellpopulations in peripheral blood will be exposed to different stimuli (such as sensitizing allergen, anti-C D3/ C D28) in vitro, type and level of reaction in the different cellpopulations will be monitored at mRNA- and protein-level. Blood sampling will be collected in connection with the visit for the baseline challenge, at the challenge at 1 years (group A-D) and 2 years (A-B).	1 and 2 years
Changes in eczema status in relation to interventions	Clinical examination including eczema grading will be performed at the food challenges and basic clinical examination at each study-visit. Eczema grading will be evaluated using Eczema area and severity index (EASI), score between 0-72.	1 and 2 years
Changes in asthma status in relation to interventions	Clinical examination including evaluation asthma status will be performed at the food challenges and basic clinical examination at each study-visit. Asthma status will be evaluated with a clinical examination, use of asthma medication, number of wheezing episodes as well as hospitalization prior to the study visit.	1 and 2 years
Changes in quality of life in relation to interventions	To evaluate changes in quality of life before and after multiallergen OIT using the "Food allergy quality of life questionnaire-parental form" (FAQLQ-PF) validated and translated into Swedish. Comparisons will be made between the OIT group and the placebo group. FAQLQ-PF is a multidimensional parent report measure to assess children between 0-12 years. There are 14 items for children below 4 years old which are scored on a 7 point scale from 0 (no impact of HRQL) to 6 (extreme impact of HRQL). FAQLQ-PF include questions for food-allergy specific QoL with general emotional impact, food anxiety, social and dietary limitations. Overall and domain specific HRQL scores will be calculated. Higher score mean worse outcome and a score of ≥ ±0.5 will be considered clinically relevant.	1 and 2 years

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Caroline Nilsson, MD, PhD, Karolinska Institutet; Principal Investigator: Anna Asarnoj, MD, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: Dnr 2024-03574-02

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