Infant Food Allergen Oral Immunotherapy
NCT Number: NCT06533462
Acronym: InFO
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Food Allergy
Interventions: DIETARY_SUPPLEMENT: Multiallergen powder
Sponsor: Karolinska Institutet
Sex: ALL
Age: CHILD
Enrollment: 80
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-12

Summary:
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.

Primary Outcome Measures: 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: 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