The Effect of Per Oral Immunotherapy in Severe IgE Mediated Egg, Milk, and Nut Allergy in Adults

• Sponsor: Helsinki University Central Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01822353
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 3
• Actual Duration (Months): 58
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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?

Condition or Disease	Intervention/Treatment	Phase
Food Allergy	Dietary Supplement: Dietary supplement	N/A

Detailed Description

Up to 100 subjects are studied. All subjects are adults having no other severe chronic diseases. The subjects belong to four different groups:

1. 30 18-50 year olds who start per oral immunotherapy treatment in severe egg allergy.

2. 30 18-50 year olds who start per oral immunotherapy treatment in severe milk allergy.

3. 30 18-50 year olds who start per oral immunotherapy treatment in severe nut allergy.

4. 10 milk allergic 18-50 year olds that have been treated as pilot patients with milk hyposensitisation treatment.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Per Oral Immunotherapy in Severe IgE Mediated Egg, Milk and Nut Allergy in Adults
• Actual Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Milk allergy Dietary supplement, milk in increasing dosages, delivered daily and orally.	Dietary Supplement: Dietary supplement; Milk, egg or nut oral immunotherapy; Other Names: Milk Egg protein Nut cream
Experimental: Egg allergy Dietary supplement, egg protein given in increasing dosages, delivered daily and orally.	Dietary Supplement: Dietary supplement; Milk, egg or nut oral immunotherapy; Other Names: Milk Egg protein Nut cream
Experimental: Nut allergy Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally.	Dietary Supplement: Dietary supplement; Milk, egg or nut oral immunotherapy; Other Names: Milk Egg protein Nut cream

Outcome Measures

Primary Outcome Measures

1. Number of the Patients That Achieve Higher Tolerance of Allergen With Immunotherapy [One year]

   Number of the patients that achieve higher tolerance of allergen with immunotherapy in one year than the measured baseline allergen challenge shows.

Secondary Outcome Measures

1. Effect of Therapy on Lung Function. [One year]

   Does hyposensitisation change lung function (do spirometry tests show difference from the baseline values (= before immunotherapy) after the immunotherapy) ?

2. Does Oral Immunotherapy Change Bronchial Hyperreactivity? [One year]

   Does bronchial hyperreactivity (measured with methacholine bronchial challenge test) show change from the baseline level after the immunotherapy?

3. Does the Oral Immunotherapy Have en Effect on Airway Inflammation? [One year]

   Does the oral immunotherapy change exhaled nitric oxide levels (measured before and after immunotherapy)

Other Outcome Measures

1. Safety of Oral Immunotherapy in Severe IgE Mediated Food Allergy in Adults. [One year]

   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?

2. Effect of Treatment on Quality of Life [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• severe IgE-mediated milk allergy or

• severe IgE-mediated egg allergy or

• severe IgE-mediated nut allergy or

• 18-50 years

Exclusion Criteria:

• instable cerebrovascular or heart disease

• active autoimmune disease or cancer

• use of betablocker agents

• poorly controlled asthma

• FEV1 < 70% of the predicted

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Helsinki University Central Hospital	Helsinki		Finland	00029

Sponsors and Collaborators

• Helsinki University Central Hospital

Investigators

• Study Director: Mika J Mäkelä, MD, PhD, Helsinki University Central Hospital

Study Documents (Full-Text)

• Study Protocol - Oct 19, 2012
• Statistical Analysis Plan - Oct 19, 2012

More Information

Publications

None provided.

• Responsible Party: Paula Kauppi, MD, PhD, MD, PhD, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT01822353
• Other Study ID Numbers: HUS21813030112
• First Posted: Apr 2, 2013
• Last Update Posted: Feb 11, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Paula Kauppi, MD, PhD, MD, PhD, Helsinki University Central Hospital: food allergy; milk allergy; egg allergy; nut allergy
• Additional relevant MeSH terms: Hypersensitivity; Food Hypersensitivity; Nut Hypersensitivity

Study Results

Participant Flow

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Period Title: Overall Study
STARTED	10	9	4
COMPLETED	6	4	3
NOT COMPLETED	4	5	1

Baseline Characteristics

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy	Total
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy	Total of all reporting groups
Overall Participants	10	9	4	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	4 100%	23 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	9 90%	6 66.7%	4 100%	19 82.6%
Male	1 10%	3 33.3%	0 0%	4 17.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Finland	10 100%	9 100%	4 100%	23 100%
Allergen specific IgE (kU/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kU/l]	57.8 (60.4)	48.8 (104.1)	22.4 (15.5)	47.7 (75.6)

Outcome Measures

1. Primary Outcome

Title	Number of the Patients That Achieve Higher Tolerance of Allergen With Immunotherapy
Description	Number of the patients that achieve higher tolerance of allergen with immunotherapy in one year than the measured baseline allergen challenge shows.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy
Measure Participants	10	9	4
Number [participants]	6 60%	4 44.4%	3 75%

2. Secondary Outcome

Title	Effect of Therapy on Lung Function.
Description	Does hyposensitisation change lung function (do spirometry tests show difference from the baseline values (= before immunotherapy) after the immunotherapy) ?
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Measure Participants	10	9	4
FEV1 (%) before OIT	91.4 (7.4)	96.1 (13.8)	86.1 (8.9)
FEV1 (%) OIT	92.1 (6.0)	96.3 (7.4)	84.0 (12.1)

3. Secondary Outcome

Title	Does Oral Immunotherapy Change Bronchial Hyperreactivity?
Description	Does bronchial hyperreactivity (measured with methacholine bronchial challenge test) show change from the baseline level after the immunotherapy?
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Drop out in the number of study individuals in the methacholine measurements at one year after OIT

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Measure Participants	10	9	4
Before OIT	531.3 (696.1)	1303.9 (1589.0)	691.2 (507.4)
After OIT	615.5 (0.0)	2059.0 (0.0)	973.4 (1029.1)

4. Secondary Outcome

Title	Does the Oral Immunotherapy Have en Effect on Airway Inflammation?
Description	Does the oral immunotherapy change exhaled nitric oxide levels (measured before and after immunotherapy)
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Measure Participants	10	9	4
Before OIT	45.3 (36.7)	25.7 (19.2)	66.6 (51.3)
After OIT	22.5 (18.9)	25.7 (18.1)	66.2 (60.2)

5. Other Pre-specified Outcome

Title	Safety of Oral Immunotherapy in Severe IgE Mediated Food Allergy in Adults.
Description	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?
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Measure Participants	10	9	4
Mild side effects	1 10%	2 22.2%	1 25%
Moderate side effects	1 10%	0 0%	0 0%
Severe side effects	0 0%	1 11.1%	0 0%
Quitting because of side effects	1 10%	2 22.2%	1 25%

6. Other Pre-specified Outcome

Title	Effect of Treatment on Quality of Life
Description	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).
Time Frame	one year

Outcome Measure Data

Analysis Population Description

Drop out in answers for quality of life at one year after OIT

Arm/Group Title	Milk Allergy	Nut Allergy	Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk oral immunotherapy	Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Nut oral immunotherapy	Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Egg oral immunotherapy
Measure Participants	10	9	4
Before OIT	83.9 (15.1)	63.5 (23.3)	61.0 (13.0)
After OIT	73.0 (5.0)

Adverse Events

Time Frame	4 years
Arm/Group Title	Milk Allergy		Nut Allergy		Egg Allergy
Arm/Group Description	Dietary supplement, milk in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy		Dietary supplement, nut cream including nut allergens, delivered in increasing dosages, daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy		Dietary supplement, egg protein given in increasing dosages, delivered daily and orally. Dietary supplement: Milk, egg or nut oral immunotherapy
All Cause Mortality
	Milk Allergy		Nut Allergy		Egg Allergy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		0/4 (0%)
Serious Adverse Events
	Milk Allergy		Nut Allergy		Egg Allergy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		1/9 (11.1%)		0/4 (0%)
Immune system disorders
Systemic allergic reaction	2/10 (20%)		1/9 (11.1%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Milk Allergy		Nut Allergy		Egg Allergy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		6/9 (66.7%)		3/4 (75%)
Gastrointestinal disorders
Mouth and throat itching	8/10 (80%)		6/9 (66.7%)		3/4 (75%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.