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In Finland, the estimated prevalence of physician-diagnosed food allergy in 1-4 year old children is 9%, and the most common allergen is milk. The overall food allergy has been reported to be 3.7%. Hen's egg allergy is among the most common food allergies in childhood. In addition, it predicts later development of allergic disease such as asthma. Most of the egg and milk allergy is transient and disappears in childhood. Currently, the standard of care for food allergy includes strict allergen avoidance. However, oral immunotherapy has been under investigation in children milk, egg, and wheat allergy. Previously, induction of clinical egg tolerance has been reported with egg oral immunotherapy in children aged from 3 to 13 years. In adults, strict avoidance is still the standard care but there is also growing interest in treatment of severe food allergy with oral immunotherapy or anti-IgE.
The investigators aim to analyse the results of per oral immunotherapy treatment in severe IgE-mediated egg, milk, and nut allergy in adults.
Could severe egg, milk and nut allergy be treated with oral immunotherapy treatment in stead of total allergen avoidance and could desensitization thus be achieved?
Up to 100 subjects are studied. All subjects are adults having no other severe chronic diseases. The subjects belong to four different groups:
The diagnosis of milk or egg allergy is verified with positive history, skin prick test, egg, milk and nut allergen specific IgE antibodies. In addition, food allergy is verified with an allergen specific challenge test.
Atopic subjects may have simultaneously other allergies. Intermittent mild asthma, and mild and moderate persistent asthma are tolerated and treatment with inhaled steroids and other asthma medication is allowed. Atopic subjects may have additional skin symptoms. Quality of life, anxiety and patient history data is collected by questionnaires. All patients undergo a spirometry with a bronchodilatation test, fractional exhaled nitric oxide and a methacholine challenge before and a year after oral immunotherapy. Those with test results diagnostic for asthma are treated with asthma medication before hyposensitisation treatment is started.
Exclusion criteria: adults with instable cerebrovascular or heart disease, active autoimmune disease or cancer, or use of betablocker agents. In addition, poorly controlled asthma or FEV1 < 70% are not tolerated.
In oral immunotherapy, increasing doses are given first observed, and then daily at home. If the subject does not tolerate a given dose and symptoms are mild, then that dose or the previously tolerated one is repeated, and the protocol proceeds as outlined. If the subject experiences significant symptoms, then the protocol is stopped, and the highest tolerated dose is used as the starting daily one.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Milk allergy | Experimental | Dietary supplement, milk in increasing dosages, delivered daily and orally. |
|
| Egg allergy | Experimental | Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. |
|
| Nut allergy | Experimental | Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dietary supplement | Dietary Supplement | Milk, egg or nut oral immunotherapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of the Patients That Achieve Higher Tolerance of Allergen With Immunotherapy | Number of the patients that achieve higher tolerance of allergen with immunotherapy in one year than the measured baseline allergen challenge shows. | One year |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Therapy on Lung Function. | Does hyposensitisation change lung function (do spirometry tests show difference from the baseline values (= before immunotherapy) after the immunotherapy) ? | One year |
| Does Oral Immunotherapy Change Bronchial Hyperreactivity? |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of Oral Immunotherapy in Severe IgE Mediated Food Allergy in Adults. | How many of the patients have side effects (categorized as mild, moderate or severe)of the hyposensitisation and how many of the patients discontinue the therapy because of side effects? | One year |
| Effect of Treatment on Quality of Life |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mika J Mäkelä, MD, PhD | Helsinki University Central Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Helsinki University Central Hospital | Helsinki | 00029 | Finland |
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| ID | Title | Description |
|---|---|---|
| FG000 | Milk Allergy | Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy |
| FG001 | Nut Allergy | Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy |
| FG002 | Egg Allergy | Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Milk Allergy | Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy |
| BG001 | Nut Allergy | Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of the Patients That Achieve Higher Tolerance of Allergen With Immunotherapy | Number of the patients that achieve higher tolerance of allergen with immunotherapy in one year than the measured baseline allergen challenge shows. | Posted | Number | participants | One year |
|
4 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Milk Allergy | Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Systemic allergic reaction | Immune system disorders | Systematic Assessment | Use of epinephrin because of allergic symptoms |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mouth and throat itching | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paula Kauppi, Chief Specialist | Helsinki University Hospital, Helsinki, Finland | +358504286802 | paula.kauppi@hus.fi |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 19, 2012 | Jun 27, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 19, 2012 | Jun 27, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005512 | Food Hypersensitivity |
| D016269 | Milk Hypersensitivity |
| D021181 | Egg Hypersensitivity |
| D021184 | Nut Hypersensitivity |
| ID | Term |
|---|---|
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000074924 | Nut and Peanut Hypersensitivity |
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| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D008892 | Milk |
| D004527 | Egg Proteins |
| ID | Term |
|---|---|
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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Does bronchial hyperreactivity (measured with methacholine bronchial challenge test) show change from the baseline level after the immunotherapy? |
| One year |
| Does the Oral Immunotherapy Have en Effect on Airway Inflammation? | Does the oral immunotherapy change exhaled nitric oxide levels (measured before and after immunotherapy) | One year |
Quality of life is assessed by a questionnaire before and after immunotherapy (VAS scale on worries on allergy 0-100, 0 no worries, 100 maximal worries). |
| one year |
| Withdrawal by Subject |
|
| BG002 | Egg Allergy | Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Allergen specific IgE | Allergen specific IgE (casein/Arah 2 /ovomucoid) (kU/l). | Mean | Standard Deviation | kU/l |
|
| OG002 |
| Egg Allergy |
Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy |
|
|
| Secondary | Effect of Therapy on Lung Function. | Does hyposensitisation change lung function (do spirometry tests show difference from the baseline values (= before immunotherapy) after the immunotherapy) ? | Posted | Mean | Standard Deviation | percentage of predicted value | One year |
|
|
|
| Secondary | Does Oral Immunotherapy Change Bronchial Hyperreactivity? | Does bronchial hyperreactivity (measured with methacholine bronchial challenge test) show change from the baseline level after the immunotherapy? | Drop out in the number of study individuals in the methacholine measurements at one year after OIT | Posted | Mean | Standard Deviation | Dose of methcholine, ug | One year |
|
|
|
| Secondary | Does the Oral Immunotherapy Have en Effect on Airway Inflammation? | Does the oral immunotherapy change exhaled nitric oxide levels (measured before and after immunotherapy) | Posted | Mean | Standard Deviation | ppb | One year |
|
|
|
| Other Pre-specified | Safety of Oral Immunotherapy in Severe IgE Mediated Food Allergy in Adults. | How many of the patients have side effects (categorized as mild, moderate or severe)of the hyposensitisation and how many of the patients discontinue the therapy because of side effects? | Posted | Number | Participants | One year |
|
|
|
| Other Pre-specified | Effect of Treatment on Quality of Life | Quality of life is assessed by a questionnaire before and after immunotherapy (VAS scale on worries on allergy 0-100, 0 no worries, 100 maximal worries). | Drop out in answers for quality of life at one year after OIT | Posted | Mean | Standard Deviation | VAS score (mm) | one year |
|
|
|
| 0 |
| 10 |
| 2 |
| 10 |
| 8 |
| 10 |
| EG001 | Nut Allergy | Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy | 0 | 9 | 1 | 9 | 6 | 9 |
| EG002 | Egg Allergy | Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy | 0 | 4 | 0 | 4 | 3 | 4 |
|
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| D001628 |
| Beverages |
| D003611 | Dairy Products |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
|
| After OIT |
|
|
|
| Title | Measurements |
|---|---|
|
| Severe side effects |
|
| Quitting because of side effects |
|
| After OIT |
|
|