Cow's Milk and Hen's Egg Hyposensitization in Adults
Primary Purpose
Egg Allergy, Cow's Milk Allergy
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Specific Oral Tolerance Induction with Egg or Cow's milk
Sponsored by
About this trial
This is an interventional treatment trial for Egg Allergy
Eligibility Criteria
Inclusion Criteria:
- Allergy to Egg or Cow's milk verified by challenge history and specific IgE
Exclusion Criteria:
- Cardiovascular disease
- Active immunological disease
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
SOTI
Food Allergy follow-up
Arm Description
Specific Oral Tolerance Induction with Egg or Cow's milk
Outcomes
Primary Outcome Measures
Number of subjects with negative results
Secondary Outcome Measures
Full Information
NCT ID
NCT02083471
First Posted
March 5, 2014
Last Updated
October 29, 2015
Sponsor
Turku University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02083471
Brief Title
Cow's Milk and Hen's Egg Hyposensitization in Adults
Official Title
Cow's Milk and Hen's Egg Hyposensitization in Adults
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Unknown status
Study Start Date
April 2015 (undefined)
Primary Completion Date
May 2017 (Anticipated)
Study Completion Date
May 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Turku University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Egg, milk and cereal allergies are the most important food allergies in Finnish children, the prevalence in western countries is 1-4 %. In some individuals food-allergy is maintained in to adulthood. Recent studies suggest that specific oral tolerance induction (SOTI) provides a treatment option in children with continuing allergy with high success rates. The study aims at specific oral tolerance induction in adults allergic to cow's milk or hen's egg. Oral immunotherapy involves taking very small amounts of the allergen, and slowly increasing the amount. Consequently, an elimination diet may be wholly or partially cancelled, without the fear of serious allergic reactions. Another aim is to explore changes in antibody-mediated and cell-mediated immune response to individual components of cow's milk and egg allergens during tolerance induction and compare these with the effect of the treatment.
Detailed Description
Background
Egg, milk and cereal allergies are the most important food allergies in Finnish children, the prevalence in western countries is 1-4 %. In some individuals food-allergy is maintained in to adulthood. The mainstay of treatment of IgE-mediated milk and egg allergy is an avoidance diet and carrying an epinephrine injector in case of an allergic reaction. Avoidance diet is very difficult and has negative effects on quality of life. Accidentally having milk or egg can cause life-threatening reactions, even lead to death. Recent studies suggest that specific oral tolerance induction (SOTI) provides a treatment option in children with continuing allergy with high success rates.
It is obvious that oral immunotherapy has impact on the milk and egg specific immune responses, but the mechanisms of this treatment have been studied only little and its effects on the cell and molecular level is practically unknown. There neither are any laboratory studies to monitor the efficacy or predict the outcome in advance or at the early stages of treatment. No research data is available on the humoral IgE, IgG4 and Immunoglobulin A (IgA) responses or the cell-mediated or cytokine responses induced by the individual major cow's milk and egg allergen components during oral immunotherapy. No tools exist for forecasting the outcome of the treatment.
Aims
The study aims at specific oral tolerance induction in adults allergic to cow's milk or hen's egg. Oral immunotherapy involves taking very small amounts of the allergen, and slowly increasing the amount. Consequently, an elimination diet may be wholly or partially cancelled, without the fear of serious allergic reactions. Another aim is to explore changes in antibody-mediated and cell-mediated immune response to individual components of cow's milk and egg allergens during tolerance induction and compare these with the effect of the treatment.
Materials and methods
The study will recruit 40 adult patients with either milk or egg allergy. Eligibility criteria are: 1) adults over 16 years, 2) elevated serum levels of specific IgE (≥ 5 kU/l, (kilounit per liter) milk or egg) or a positive skin-prick- test (≥ 5 mm, milk or egg), and 3) a positive milk- or egg-challenge. The recruited subjects meeting entry criteria are randomized to a tolerance induction group receiving milk or egg (n = 20) or to a control group to be followed on an avoidance diet (n = 20). Oral immunotherapy involves initially taking a very small amount of the allergen, and slowly increasing the amount gradually until a maintenance dose is reached. Up-dosing is monitored in hospital. Thereafter, the patient will continue the daily use of milk or egg at home.
Skin-prick-tests with milk or egg specific allergen components are performed, a symptom questionnaire is filled and blood samples are taken before commencement of the study, when the maintenance dose is reached and after 12 months from initiation of the study. Patient visits are carried out in outpatient clinic as part of the normal routine.
Commercially available (Thermo Fisher Scientific Phadia) specific allergen components are examined (IgE and IgG4), as well as IgA, IgA1 and IgA2. Cow's milk allergen components are: alfa-lactalbumin, beta-lactoglobulin, casein, lactoferrin and bovine serum albumin, and egg allergen components are: ovomucoid, ovalbumin, conalbumin and lysozyme.
Mononuclear leukocytes are isolated from the blood samples and cultured in 37 ° C incubator 10^6 cells per millilitre of RPMI (Roswell Park Memorial Institute Medium) medium containing 5% autologous plasma and cows' milk allergen components: alfa-lactalbumin, beta-lactoglobulin, bovine serum albumin, casein and lactoferrin, or egg allergen components: ovomucoid, ovalbumin, conalbumin and lysozyme. Mitogen is used as the positive control and medium without stimulation as the negative control. Milk and egg allergen components are cleaned with Detoxi-Gel Endotoxin Removal Gel columns (Thermo Scientific Pierce Chemicals) to remove effects of endotoxins during cell stimulation. Lymphoproliferation is studied using three parallel samples and cytokine expression is studied using two parallel samples (Luminex/Lincoplex: interleukin-4 (IL-4), IL-5, IL-10, IL-12, IL-13, IL-17, IL-18, IL-22, IL-23, IL-27, interferon gamma(IFN-γ), tumor necrosis factor (TNF) and transforming growth factor beta (TGF-β)).
Ethical considerations
Study follows instructions and regulations used in biomedical research. The Turku University Ethics committee approved the study 15th February 2011. Each participant will give written informed consent. Research participation is voluntary and may be suspended without any reason at any time during the study and the refusal or termination shall not affect the patient's other treatment. Patient samples and the data collected are processed and stored according to the instructions and regulations used in biomedical research.
Estimate, schedule and results
Patient visits are carried out in outpatient clinics as part of the normal reception of allergy patients and do not entail additional costs to the patients. The expenses related to antibody-mediated and cell-mediated immune response studies are covered by external funding. The study will begin in autumn 2014 and aims being completed in the spring of 2016. The results will be published in international scientific journals.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Egg Allergy, Cow's Milk Allergy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SOTI
Arm Type
Active Comparator
Arm Description
Specific Oral Tolerance Induction with Egg or Cow's milk
Arm Title
Food Allergy follow-up
Arm Type
No Intervention
Intervention Type
Dietary Supplement
Intervention Name(s)
Specific Oral Tolerance Induction with Egg or Cow's milk
Primary Outcome Measure Information:
Title
Number of subjects with negative results
Time Frame
12 months after commencement
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Allergy to Egg or Cow's milk verified by challenge history and specific IgE
Exclusion Criteria:
Cardiovascular disease
Active immunological disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johannes Savolainen, MD Professor
Phone
407172029
Ext
+358
Email
johannes.savolainen@tyks.fi
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johannes Savolainen, MD Professor
Organizational Affiliation
University of Turku
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Cow's Milk and Hen's Egg Hyposensitization in Adults
We'll reach out to this number within 24 hrs