High and Low Dose Oral Peanut Immunotherapy - Comparison of Efficacy and Safety

Study Overview
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Brief Summary
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In this trial the investigators aim to assess the effectiveness and safety of oral immunotherapy with peanut protein in high and low dose (300mg versus 150mg) in children with peanuts allergy.

Detailed Description
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Peanut allergy is a significant clinical problem. Food immunotherapy provides the latest approach to managing food allergy. Oral immunotherapy is considered as the most effective and safe, according to current research. What is more, this type of therapy is easily available and can be continued at patient's home. Obtaining and maintenance of tolerance to the allergic food is the main goal of this procedure. The study will include children with peanut allergy, confirmed during open oral food challenge (OOFC) with peanut protein. First OOFC will be performed before immunotherapy, second one at the end of procedure. Participants will be randomly assigned to two groups. During the maintenance phase, the first group will receive low dose of peanut protein, which amounts 150mg, the second will get high dose, which is 300 mg of peanut protein. Oral immunotherapy with low and high dose of peanut protein in children randomly assigned to two groups (1:1). In the following phase, every two weeks the dose of ground roasted peanut will be increased and applied to a child during hospitalization (1-day procedure). Precondition to increase of dose is good tolerance of previous portion of peanut. The maximum time frame for this phase is 14 months. After achieving tolerance, immunotherapy will be continued for 2 months in maintenance phase, with dose 150mg or 300 mg peanut protein, depending on a study group. The dosage increasing phase will last maximally 14 months. If patients achieves the maintenance dose earlier, this period may be shorter. Maintenance dose is determined by random patients' assignment to one from study's group and amounts 150mg or 300 mg of peanut protein, respectively. The duration of the maintenance phase is 8 weeks (+/-2 weeks). After 2 months (8 weeks +/-2 weeks) of maintenance dose the final OOFC and evaluation of tolerance of peanut protein will be performed. Confirmation of the total desensitization of peanut is the tolerance of a single dose of 4500 mg peanut protein.

Official Title
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High and Low Dose Oral Peanut Immunotherapy - Comparison of Efficacy and Safety

Conditions
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Peanut Allergy

Intervention / Treatment
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* Dietary Supplement: High dose of peanuts
* Dietary Supplement: Low dose of peanuts


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: medical history of peanut allergy, IgE-mediated peanut allergy confirmed as positive skin prick tests with peanut allergens (diameter of the wheal greater than 3mm) and/or specific IgE level greater than 0.35 kilo units of Allergen per liter (kUA/l) (UniCAP method), reaction to less than 100 mg of peanut protein during OOFC, signed Informed Consent by parent/legal guardian and patient aged >16 years old, patient's/caregivers' cooperation with researcher. Exclusion Criteria: no confirmed peanut allergy, negative oral food challenge with less than 100mg of peanut protein, severe asthma, uncontrolled mild/moderate asthma: forced expiratory volume at one second (FEV1)<80% (under 5. percentile), FEV1/forced vital capacity (FVC)<75% (under 5. percentile), hospitalization due to asthma exacerbation within last 12 months, current oral/sublingual/subcutaneous immunotherapy with other allergen, eosinophilic gastroenteritis, a history of severe recurrent anaphylaxis episodes, chronic diseases requiring continuous treatment, including heart disease, epilepsy, metabolic diseases, diabetes, medication: oral, daily steroid therapy longer than 1 month within last 12 months, at least two courses of oral steroid therapy (at least 7 days) within last 12 months, oral steroid therapy longer than 7 days within last 3 months, biological treatment, the need to constantly take antihistamines, therapy with β-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium channel inhibitors, pregnancy, no consent to participate in the study, lack of patient cooperation.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to two groups. During the maintenance phase, the first group will receive low dose of peanut protein, which amounts 150mg, the second will get high dose, which is 300 mg of peanut protein. Oral immunotherapy with low (150mg) and high (300mg) dose of peanut protein in children randomly assigned to two groups (1:1). Patients will receive ground peanuts mixed with apple mousse (supposing apple tolerance). For the transparency of the study all patients will receive the same commercially prepared apple muss product.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high dose of peanut<br>20 patients | Dietary Supplement: High dose of peanuts<br>* Patients will receive a high dose of ground peanuts (300 mg) mixed with apple mousse (supposing child tolerates apple). For the transparency of the study all patients will receive the same commercially prepared apple product<br>|
| Active Comparator: low dose of peanuts<br>20 patients | Dietary Supplement: Low dose of peanuts<br>* Patients will receive a low dose of ground peanuts (150 mg) mixed with apple mousse (supposing child tolerates apple). For the transparency of the study all patients will receive the same commercially prepared apple product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of peanuts | Proportion of participants who tolerate the single dose of 300 mg or more (maximum 4500mg) peanut protein | Up to 16 months after starting oral immunotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event | quantity and severity of adverse effect, assessed and compared between groups, divided into mild, moderate and severe category | Up to 16 months after starting oral immunotherapy | 
| Laboratory data | difference in peanut serum immunoglobulin E (IgE) level and immunoglobulin G4 (IgG4) level, compared between groups at the end of treatment | Up to 16 months after starting oral immunotherapy | 
| Skin prick test (SPT) | change in skin prick test reactivity to peanut protein from baseline to end of treatment, compared between groups | Up to 16 months after starting oral immunotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peanuts, food allergy, immunotherapy, children