High and Low Dose Oral Sesame 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 sesame protein in high and low dose (300mg versus 1200mg) in children with sesame allergy.

Detailed Description
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Sesame allergy is an important global clinical problem affecting 0,2-0,8% population. In food allergy, allergen avoidance and emergency treatment are still therapeutic hallmarks. Oral and sublingual allergen-specific immunotherapies have been provided as a new approach to managing food allergy. The main goal of oral immunotherapy is to obtain the desensitization to food. The oral immunotherapy (OIT) is considered as safe and highly effective, according to current research. In addition, this type of therapy reduce the influence of food allergy in patient's live. Children 4 to 17 years old with sesame allergy will be enrolled into study. Skin prick test with condiment made from toasted ground hulled sesame and open oral food challenge (OOFC) will be performed at the baseline and at the end of procedure. Blood will be analyzed for specific IgE, IgG4 levels and basophil activation test before and after OIT. OIT will consisted of two parts: dosage increase phase and maintenance phase. The Participants will be randomized (1:1) to receive sesame OIT with maintenance dose of 300 mg or 1200 mg sesame protein. In the dosage increase phase, the dose of condiment made from toasted ground hulled sesame will be gradually increased every two weeks and administrated to a child during hospitalization (1-day procedure). Precondition to increase of dose is good tolerance of previous portion of condiment made from toasted ground hulled sesame. The maximum time frame for this phase is 14 months. After achieving tolerance, immunotherapy will be continued for 3 months in maintenance phase, with dose 300mg or 1200 mg sesame protein. Maintenance dose is determined by random patients' assignment to one from study's . After 3 months (12 weeks +/-2 weeks) of maintenance dose the final OOFC and evaluation of desensitization of sesame protein will be performed. Confirmation of the total desensitization to sesame is the tolerance of a single dose of 4000 mg sesame protein.

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

Conditions
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Food Allergy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: medical history of sesame allergy, IgE-mediated sesame allergy confirmed as positive skin prick tests with sesame 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 sesame protein during OOFC (maximum dose 4000g), signed Informed Consent by parent/legal guardian and patient aged >16 years old, patient's/caregivers' cooperation with researcher. Exclusion Criteria: no confirmed sesame allergy, negative oral food challenge with sesame protein (maximum dose 4000g), 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 sesame protein, which amounts 300mg, the second will get high dose, which is 1200 mg of sesame protein. Oral immunotherapy with low (300mg) and high (1200mg) dose of sesame protein in children randomly assigned to two groups (1:1). Patients will receive ground sesame 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<br>Experimental: high dose of sesame 20 patients | Dietary Supplement: High dose<br>* Patients will receive a high dose of sesame paste or flour (1200 mg of sesame protein) 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<br>Active Comparator: low dose of sesame 20 patients | Dietary Supplement: Low dose<br>* Patients will receive a low dose of sesame paste or flour (300 mg of sesame protein) 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 sesame | Proportion of participants who tolerate the single dose of 4000mg sesame 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 sesame 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 | 
| Basophil activation test | The basophil activation test (BAT) results 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 sesame protein from baseline to end of treatment, compared between groups | Up to 16 months after starting oral immunotherapy | 
| Desensitization dose | Change in maximum tolerated dose of sesame in oral food challenge before and in the 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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sesame, food allergy, immunotherapy, children