Oral Desensitization to Wheat in School Aged Children

Oral Desensitization to Wheat in Children Over 6 Years of Age With Wheat Allergy

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.

Study Overview

• Status: Completed
• Conditions: Wheat Allergy
• Intervention / Treatment: Dietary supplement: Wheat oral immunotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital
  • Kuopio, Finland, 70211
    • Kuopio University Hospital
  • Oulu, Finland, 90014
    • University of Oulu
  • Tampere, Finland, 33521
    • Tampere University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Wheat oral immunotherapy; 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.	Dietary supplement: Wheat oral immunotherapy; Cooked spaghetti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of oral wheat desensitization	Change in the tolerance to wheat and the amount of daily use of wheat in 3 months after the 5 months oral desensitization therapy.	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of oral wheat desensitization at 17 months	Change in the tolerance to wheat and the amount of daily use of wheat in 1 year after the 5 months oral desensitization therapy.	17 months
Safety of oral wheat desensitization therapy at 8 months	Number of participants with adverse events as a measure of tolerability and safety at 3 months after the 5 months desensitization therapy	8 months
Safety of oral wheat desensitization therapy at 17 months	Number of participants with adverse events as a measure of tolerability and safety at 1 year after the 5 months desensitization therapy	17 months
Effect of the treatment on the characteristics and function of immune cells	Flow cytometric characterization of the change in the proportions of various T cell subtypes and in the function of these cells in in vitro proliferation and suppression tests between the samples taken before the treatment and 3 and 12 months after the treatment.	17 months
Effect of the treatment on the cell specific mRNA expression	qRT-PCR measurement of the change in the expression level of T cell subtype specific mRNA levels between the samples taken before the treatment and 3 and 12 months after the treatment.	17 months
Effect of the treatment on the cytokine profile	Flow cytometric measurement of the change in the levels of T cell subtype specific cytokine levels between the samples taken before the treatment and 3 and 12 months after the treatment.	17 months

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: Oulu University Hospital; Kuopio University Hospital; Tampere University Hospital; University of Oulu
• Investigators: Principal Investigator: Mika J Mäkelä, MD, PhD, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: December 19, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (ESTIMATE): December 24, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 20, 2015
• Last Update Submitted That Met QC Criteria: March 19, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Immunotherapy; Desensitization; T cells; Food allergy; Wheat allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Wheat Hypersensitivity
• Other Study ID Numbers: ODEW