T502: Determination of the Sensitivity and Specificity of Prick Test Betula Verrucosa

• Sponsor: Inmunotek S.L. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02527187
• Collaborator: (none)
• Enrollment: 201
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 14.3

Study Details

Study Description

Brief Summary

The main objective is to evaluate the concentration of allergen extract of Betula verrucosa that elicit a papule equivalent to that produced by a solution of histamine dihydrochloride 10 mg / ml in size.

Condition or Disease	Intervention/Treatment	Phase
Immune System Diseases	Biological: 10 HEP/mL Betula verrucosa allergen extract; Biological: 25 HEP/mL Betula verrucosa allergen extract; Biological: 50 HEP/mL Betula verrucosa allergen extract; Biological: 100 HEP/mL Betula verrucosa allergen extract	Phase 2

Detailed Description

Open, prospective, unblinded and non-randomized biological assay. Each patient was tested with four concentrations of allergen and with a histamine and saline solution as positive and negative controls, respectively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Extract Allergen From Betula Verrucosa. Test Sensitivity and Specificity of Diagnostic in Prick Test Preparation.
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allergic patients to birch pollen Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Biological: 10 HEP/mL Betula verrucosa allergen extract; The investigational product contained 10 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 25 HEP/mL Betula verrucosa allergen extract; The investigational product contained 25 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 50 HEP/mL Betula verrucosa allergen extract; The investigational product contained 50 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 100 HEP/mL Betula verrucosa allergen extract; The investigational product contained 100 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.
Experimental: Non-allergic patients to birch pollen Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.	Biological: 10 HEP/mL Betula verrucosa allergen extract; The investigational product contained 10 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 25 HEP/mL Betula verrucosa allergen extract; The investigational product contained 25 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 50 HEP/mL Betula verrucosa allergen extract; The investigational product contained 50 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.; Biological: 100 HEP/mL Betula verrucosa allergen extract; The investigational product contained 100 HEP/mL Betula verrucosa allergen extract and was tested by administration onto skin. The test was carried out on the forearm following prick test technique.

Outcome Measures

Primary Outcome Measures

1. Sensitivity for 100 HEP/mL [1 hour]

   Sensitivity for 100 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease

2. Sensitivity for 50 HEP/mL [1 hour]

   Sensitivity for 50 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease

3. Sensitivity for 25 HEP/mL [1 hour]

   Sensitivity for 25 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease

4. Sensitivity for 10 HEP/mL [1 hour]

   Sensitivity for 10 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease

5. Specificity for 100 HEP/mL [1 hour]

   Specificity for 100 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.

6. Specificity for 50 HEP/mL [1 hour]

   Specificity for 50 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.

7. Specificity for 25 HEP/mL [1 hour]

   Specificity for 25 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.

8. Specificity for 10 HEP/mL [1 hour]

   Specificity for 10 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

General inclusion criteria for both groups:

• Positive skin prick test with the positive control (Histamine HCl at 10 mg/mL). The length of the largest diameter of the wheal induced by this control should be ≥ 3 mm.

• Negative skin prick test with the negative control. The length of the largest diameter of the wheal induced by this control should be < 3 mm.

• All ages and both genders.

For the group of patients CH+ (true positive to Betula verrucosa): All these patients had a previous diagnosis of allergy to the birch pollen:

• A positive case history with inhalant allergy related to exposure to birch pollen.

• A positive skin prick test (mean wheal diameter ≥ 3 mm) when tested with a biologically standardized extract prepared from birch pollen. This preparation, from another manufacturer, was the one used in the routine in the Hospital.

• Positive test for specific IgE (CAP value > 0.35 IU/mL). For the group of patients CH- (true negative to Betula verrucosa): All these patients had a previous diagnosis of allergy to agents unrelated to birch pollen.

• A negative case history with inhalant allergy related to exposure to birch pollen or to pollen with known cross-reactivity with the birch pollen. These patients could be allergic to other pollen or other allergens, such mites.

• A negative prick test (largest diameter of the wheal ≥ 3 mm) when tested with a standardized extract prepared from the allergen source in question.

• A negative test for specific IgE (CAP value < 0.35 IU/mL) to birch pollen or to pollen with known cross-reactivity with birch pollen: Corylus avellana, Quercus verrucosa, Fagus sylvatica, Castanea satavia, Carpinus betelus and Alnus glutinosa.

Exclusion criteria for both groups:

• Patients that were using drugs that may interfere with the skin prick tests.

• Patients using the following drugs 24 hours before the test: theophylline, systemic corticosteroids.

• Patients in which the largest diameter of the wheal induced by the positive control was < 3 mm.

• Patients in which the largest diameter of the wheal induced by the negative control was ≥ 3 mm.

• Pregnancy, dermographism, atopic dermatitis (locally at the test site), urticaria.

• Patients who suffer disease in which the use of adrenaline is not allowed.

• Patients with any severe psychiatric disease.

For the patients CH+:

• Patients that received or are treated with immunotherapy with an allergenic extract of birch pollen and/or with allergen extracts with known cross-reactivity to birch pollen (Corylus avellana, Quercus verrucosa, Fagus sylvatica, Castanea satavia, Carpinus betelus and Alnus glutinosa).

For the patients CH-:

• Patients sensitized to pollen with demonstrated cross-reactivity with the pollen of Betula verrucosa. These pollen included Corylus avellana, Quercus verrucosa, Fagus sylvatica, Castanea satavia, Carpinus betelus and Alnus glutinosa.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Lucus Augusti	Lugo	Galicia	Spain	27003

Sponsors and Collaborators

• Inmunotek S.L.

Investigators

• Study Director: Manuel Boquete, MD,

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Inmunotek S.L.
• ClinicalTrials.gov Identifier: NCT02527187
• Other Study ID Numbers: T502-SSP-007; 2013-005368-24
• First Posted: Aug 18, 2015
• Last Update Posted: May 5, 2022
• Last Verified: May 1, 2022

• Keywords provided by Inmunotek S.L.: Immune System Diseases; Prick Test; Betula verrucosa
• Additional relevant MeSH terms: Immune System Diseases

Study Results

Participant Flow

Recruitment Details	Screening based on subjects already diagnosed as allergic or not to birch pollen. (See Inclusion criteria section)

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Period Title: Overall Study
STARTED	75	126
COMPLETED	75	126
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen	Total
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.	Total of all reporting groups
Overall Participants	75	126	201
Age (Count of Participants)
<=18 years	10 13.3%	12 9.5%	22 10.9%
Between 18 and 65 years	60 80%	104 82.5%	164 81.6%
>=65 years	5 6.7%	10 7.9%	15 7.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.2 (15.5)	40.8 (14.3)	39.8 (14.8)
Sex: Female, Male (Count of Participants)
Female	42 56%	80 63.5%	122 60.7%
Male	33 44%	46 36.5%	79 39.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	75 100%	126 100%	201 100%
Region of Enrollment (participants) [Number]
Spain	75 100%	126 100%	201 100%
positive skin prick test (diameter of the wheal > 3mm) (Count of Participants)
Count of Participants [Participants]	75 100%	126 100%	201 100%

Outcome Measures

1. Primary Outcome

Title	Sensitivity for 100 HEP/mL
Description	Sensitivity for 100 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [positive reaction]	75	0

2. Primary Outcome

Title	Sensitivity for 50 HEP/mL
Description	Sensitivity for 50 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [positive reaction]	74	0

3. Primary Outcome

Title	Sensitivity for 25 HEP/mL
Description	Sensitivity for 25 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [positive reaction]	63	0

4. Primary Outcome

Title	Sensitivity for 10 HEP/mL
Description	Sensitivity for 10 HEP/mL concentration of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of positives that are correctly identified by the test. Sensitivity: True positives/Total disease
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [positive reaction]	58	0

5. Primary Outcome

Title	Specificity for 100 HEP/mL
Description	Specificity for 100 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [Negative response]	0	126

6. Primary Outcome

Title	Specificity for 50 HEP/mL
Description	Specificity for 50 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [Negative response]	0	126

7. Primary Outcome

Title	Specificity for 25 HEP/mL
Description	Specificity for 25 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years. The investigational product contained the allergen extract of the pollen of Betula verrucosa and will be tested by administration onto skin. The test will be carried out on the forearm following prick test technique.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years. The investigational product contained the allergen extract of the pollen of Betula verrucosa and will be tested by administration onto skin. The test will be carried out on the forearm following prick test technique.
Measure Participants	75	126
Number [Negative response]	12	126

8. Primary Outcome

Title	Specificity for 10 HEP/mL
Description	Specificity for 10 HEP/mL concentrations of the pollen of Betula verrucosa allergen extract used in skin prick test. It is the proportion of negatives that are correctly identified by the test. Specificity: True negatives/Total no disease.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allergic Patients to Birch Pollen	Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.	Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
Measure Participants	75	126
Number [Negative response]	16	126

Adverse Events

Time Frame	Up to 1 hour after performing test and up to 5 days after release from the hospital.
Adverse Event Reporting Description	In terms of safety, although skin prick tests are safe and patients were already tested previously in the hospital, the investigator took special care in order to check for the presence of any unwanted reaction. Patients remained in the hospital facilities (around 30 min-1 hour after test) and were instructed to report, to the investigator, any adverse event occurring after leaving the hospital.
Arm/Group Title	Allergic Patients to Birch Pollen		Non-allergic Patients to Birch Pollen
Arm/Group Description	Allergic patients already diagnosed to be "true allergic" to birch pollen. A mean wheal diameter >3 mm obtained in a prick test with histamine dihydrochloride 10 mg/ml.Also presence of serum specific IgE and clinical history of symptomatology related to exposure to birch pollen. Patients of both gender aged from 5 up to 70 years.		Patients already diagnosed to be "true non-allergic" to birch pollen. Non clinical history of symptomatology related to the exposure to birch pollen. Previous skin prick test negative and absence or undetectable serum specific IgE to Betula verrucosa Patients of both gender aged from 5 up to 70 years.
All Cause Mortality
	Allergic Patients to Birch Pollen		Non-allergic Patients to Birch Pollen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/126 (0%)
Serious Adverse Events
	Allergic Patients to Birch Pollen		Non-allergic Patients to Birch Pollen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/126 (0%)
Other (Not Including Serious) Adverse Events
	Allergic Patients to Birch Pollen		Non-allergic Patients to Birch Pollen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/126 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.