Induction of Sustained Unresponsiveness to Sesame Using High- and Low-dose Sesame Oral Immunotherapy

Official title

Induction of Sustained Unresponsiveness to Sesame Using High- and Low-dose Sesame Oral Immunotherapy - Evaluation of Efficacy and Safety

Overview

This is an experimental, interventional study, following on from a clinical trial comparing the efficacy and safety of oral immunotherapy with low and high doses of sesame protein, in which patient desensitisation was achieved (High and Low Dose Oral Sesame Immunotherapy - Comparison of Efficacy and Safety, NCT05158413). The aim of this study is to assess a sustained unresponsiveness (SU) to sesame protein after at least 8 months of previously assigned high- or low-dose sesame OIT, followed by 4-week-allergen avoidance, and verified by an open oral food challenge (OOFC).

Detailed description

Oral immunotherapy is considered the most effective treatment for food allergy. There are two main goals of food immunotherapy: achievement of desensitisation and sustained unresponsiveness.

Desensitisation involves achieving temporary tolerance of the allergenic food by the patient only during regular intake of the allergen. The most desirable effect of immunotherapy is to achieve sustained unresponsiveness, i.e. to maintain the absence of adverse symptoms to a given allergen after specific immunotherapy has been discontinued for a defined period of time.

The study is a continuation of a clinical trial NCT05158413 which was designed to compare the efficacy and safety of oral immunotherapy (OIT) with low or high doses of sesame protein (300 or 1200 mg, respectively) in children with a confirmed diagnosis of sesame allergy. The participants of current study will be recruited from patients who have accomplished their per-protocol participation in previous trial.

Patients will receive the same maintenance dose of sesame allergen, which was used in previous trial (300 or 1200 mg, respectively), for 32 weeks (+/-2 weeks). Then, OIT will be discontinued for 4 weeks with strict sesame avoidance. Subsequently, an open oral food challenge (OOFC) will be performed to assess the achievement of sustained unresponsiveness.

Interventions

• Dietary supplement High dose OIT
  Patients will receive daily a high dose of the sesame paste (1200 mg sesame protein) mixed with well-tolerated fruit mousse or bread.
• Dietary supplement Low dose OIT
  Patients will receive daily a low dose of the sesame paste (300 mg sesame protein) mixed with well-tolerated fruit mousse or bread.

Primary outcome measures

• Sustained unresponsiveness to a sesame protein after discontinuing oral immunotherapy for 4 weeks. [Time frame: Up to 9 months after starting maintenance phase]
• The highest tolerated dose of sesame protein after discontinuing oral immunotherapy for 4 weeks. [Time frame: Up to 9 months after starting maintenance phase]

Secondary outcome measures (4)

• Adverse events [Time frame: Up to 9 months after starting maintenance phase]
• Laboratory data [Time frame: Up to 9 months after starting maintenance phase]
• Skin prick test (SPT) [Time frame: Up to 9 months after starting maintenance phase]
• Tolerance of a single dose of 4000 mg of sesame protein [Time frame: Up to 9 months after starting maintenance phase]

Eligibility criteria

Inclusion criteria

• patients who have accomplished their per-protocol participation in trial NCT05158413.
• signed Informed Consent by parent/legal guardian and patient aged>16 years old
• patient's/caregiver's cooperation with researcher

Exclusion criteria

• severe asthma
• uncontrolled mild/moderate asthma: forced expiratory volume at one second (FEV1)<80% (under 5 percentile), FEV1/forced vital capacity (FEV)<75% (under 5 percentile), hospitalization due to asthma exacerbation within last 12 months
• current oral/sublingual/subcutaneous immunotherapy with another allergen
• eosinophilic esophagitis
• allergic reaction of 4th or higher grade according to the World Allergy Organisation Systemic Allergic Reaction Grading System during immunotherapy
• a history of severe recurrent anaphylaxis episodes
• chronic diseases requiring continous treatment, including heart disease, epilepsy, metabolic disease, diabetes
• medication:

• oral, daily steroid therapy exceeding 1 month within the last 12 months
• at least two courses of oral steroid therapy (at least 7 days) within the last 12 months
• oral steroid therapy longer than 7 days within the last 3 months
• biological treatment
• the need to constantly take antihistamines
• therapy with b-blockers, angiotensin converting enzyme (ACE) inhibitors, calcium channel inhibitors
• pregnancy
• no consent to participate in the study
• lack of patient cooperation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 1 center

• Medical University of Warsaw — Warsaw

Publications

• Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012 Dec;130(6):1260-74. d PMID 23195525
• Pajno GB, Fernandez-Rivas M, Arasi S, Roberts G, Akdis CA, Alvaro-Lozano M, Beyer K, Bindslev-Jensen C, Burks W, Ebisawa M, Eigenmann P, Knol E, Nadeau KC, Poulsen LK, van Ree R, Santos AF, du Toit G, Dhami S, Nurmatov U, Boloh Y, Makela M, O'Mahony L, Papadopoulos N, Sackesen C, Agache I, Angier E, Halken S, Jutel M, Lau S, Pfaar O, Ryan D, Sturm G, Varga EM, van Wijk RG, Sheikh A, Muraro A; EAAC PMID 29205393
• Adatia A, Clarke AE, Yanishevsky Y, Ben-Shoshan M. Sesame allergy: current perspectives. J Asthma Allergy. 2017 Apr 27;10:141-151. doi: 10.2147/JAA.S113612. eCollection 2017. PMID 28490893
• Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA. Treatment for food allergy. J Allergy Clin Immunol. 2018 Jan;141(1):1-9. doi: 10.1016/j.jaci.2017.11.004. PMID 29307409
• Nachshon L, Goldberg MR, Levy MB, Appel MY, Epstein-Rigbi N, Lidholm J, Holmqvist M, Katz Y, Elizur A. Efficacy and Safety of Sesame Oral Immunotherapy-A Real-World, Single-Center Study. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2775-2781.e2. doi: 10.1016/j.jaip.2019.05.031. Epub 2019 May 29. PMID 31150789
• Dalal I, Goldberg M, Katz Y. Sesame seed food allergy. Curr Allergy Asthma Rep. 2012 Aug;12(4):339-45. doi: 10.1007/s11882-012-0267-2. PMID 22610362

Identifiers

NCT: NCT05923216 · Sesame Protocol - SU

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗