Clinical trial NCT01755884: Oral Desensitization to Wheat in School Aged Children
Official title: Oral Desensitization to Wheat in Children Over 6 Years of Age With Wheat Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Wheat Allergy
Keywords: Wheat allergy
Immunotherapy
Desensitization
Food allergy
T cells
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Oulu
name: Oulu University Hospital
name: Tampere University Hospital
name: Kuopio University Hospital
First posted: 2012-12-24
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study is to induce tolerance to wheat in wheat allergic children via oral desensitization therapy. The hypothesis is that oral administration of wheat with increasing dosing will increase the individual threshold for allergic reactivity to wheat protein (i.e. desensitization) and even result in no reactivity (i.e. full tolerance). Along with this, the risk for severe allergic reaction to wheat protein is minimized and the diet of patients can partly or completely be normalized. In addition to clinical measures, the immunological mechanisms of desensitization therapy are studied in detail at cellular and molecular level.

Detailed description: This is a prospective multicenter study investigating the efficacy, safety and immunological mechanisms of oral wheat desensitization therapy in school-aged (6-16 yrs of age) wheat allergic children. Wheat allergic children with avoidance diet, immediate reaction in a recent (less than 4 months) food challenge test for wheat and elevated serum wheat-specific IgE levels are recruited to the study. Patients having uncontrolled asthma, other lung disease, cardiovascular disease or other significant systemic disease and patients having poor compliance are excluded. Well-cooked wheat spaghetti is given daily to the patients starting from a minimal dosage (0,0003 g of wheat protein) and increasing the dosing in every 1-2 weeks until a dosage corresponding the size of one meal. The initial dosage is given and certain defined dosage step-ups are carried out in the hospital outpatient clinic. The patient and parents are prepared for the emergency treatment of severe allergic reaction and carry adequate medication with them. The daily use of spaghetti continues with the received maintenance dosage for additional 3 months, until the clinical evaluation of the patient. Thereafter, the patients are allowed to use also other wheat products. Peripheral venous blood samples are taken before therapy and at 3 months and 1 year follow-up visits after reaching the maintenance dosage. The characteristics and function of isolated peripheral blood mononuclear cells (PBMC) will be specifically tested using flow cytometric methods. The expression levels of cell-specific mRNAs (messenger ribonucleic acid) and cytokines are measured with qRT-PCR (quantitative reverse transcriptase real-time polymerase chain reaction)and flow cytometry based methods. In addition, specific IgE (immunoglobulin E) levels are measured and serum samples are frozen for further testing. Two separate control groups are also recruited. The first group includes patients with previous food-challenge proven IgE-mediated wheat allergy with spontaneous recovery and the current free use of wheat protein in their diet. The second group includes children (6-16 yrs of age) who come to hospital for a minor surgical operation (e.g. minor trauma, circumcision, patellar luxation etc.). Children with asthma, allergy, atopic eczema, any other chronic disease or recent infection (less than 2 weeks ago) are excluded from this group. Peripheral venous blood samples are taken from all control children. The characteristics and function of isolated PBMCs, the expression levels of cell-specific mRNAs and cytokines and specific IgE levels are measured.

Eligibility criteria: Inclusion Criteria:

* Elevated serum wheat specific IgE
* Immediate reaction in open oral wheat challenge test
* Diet free from wheat, rye, and barley

Exclusion Criteria:

* Uncontrolled asthma
* Other lung disease
* Cardiovascular disease or other significant systemic disease
* Patients having poor compliance

Primary outcomes:
measure: Efficacy of oral wheat desensitization
timeFrame: 8 months
Secondary outcomes:
measure: Efficacy of oral wheat desensitization at 17 months
timeFrame: 17 months
measure: Safety of oral wheat desensitization therapy at 8 months
timeFrame: 8 months
measure: Safety of oral wheat desensitization therapy at 17 months
timeFrame: 17 months
measure: Effect of the treatment on the characteristics and function of immune cells
timeFrame: 17 months
measure: Effect of the treatment on the cell specific mRNA expression
timeFrame: 17 months
measure: Effect of the treatment on the cytokine profile
timeFrame: 17 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: University of Oulu
city: Tampere
country: Finland
facility: Tampere University Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Mika J Mäkelä, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: