Allergy, Hookworm Infection
Conditions
Keywords
Hookworm, Allergy, Vaccine, Skin test
Brief summary
Na-ASP-2 is a protein expressed during the larval stage of the N. americanus hookworm life cycle. In a clinical study in previously hookworm-infected adults in Brazil, this protein induced urticarial reactions (rash) in a subset of volunteers. This study will evaluate solutions of varying concentrations of the protein in both a skin prick-puncture and intradermal test that will eventually be used to screen volunteers living in hookworm endemic areas who are being considered as potential participants in vaccine trials, to reduce the potential of inducing allergic reactions in those vaccinated with the Na-ASP-2 Hookworm Vaccine.
Detailed description
* Study site: George Washington University Medical Center * Number of participants: up to 15 * Study duration: up to 3 months; each participant will undergo a minimum of one screening visit and one study visit. * Each participant will have both skin prick-puncture and intradermal skin tests applied on the same study day. The prick-puncture and intradermal tests will be applied sequentially to the volar aspects of the participant's forearms: 1. Skin prick-puncture: four different concentrations of Na-ASP-2 solution (1, 10, 100, and 1000 μg/mL) will be applied simultaneously in duplicate, to the left forearm. 2. Intradermal: three different concentrations of Na-ASP-2 (10, 100, and 1000 μg/mL) will be injected simultaneously, in duplicate, to the right forearm. 3. Allergen diluent and histamine solutions will be utilized as the negative and positive controls, respectively, for both the skin prick-puncture and intradermal tests. 4. Participants will be observed in the study clinic for at least 30 minutes following application of the skin tests, and will be contacted via telephone 2 days following skin testing. 5. Sizes of the wheal and erythema reactions for each application will be recorded and graded in comparison to the histamine positive control reaction. * Each participant will have blood collected via venipuncture (a maximum of 25 mL) immediately prior to application of the skin tests, in order to measure antibodies (particularly IgG and IgE) to Na-ASP-2 using an ELISA procedure.
Interventions
BIOLOGICALNa-ASP-2 Skin Test Reagent
Na-ASP-2 Hookworm Skin Test Reagent, 1-1000 mcg/mL solution
Sponsors
Albert B. Sabin Vaccine Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females between 18 and 45 years of age, inclusive. * Good general health as determined by means of the screening procedure. * Willingness to participate in the study as evidenced by signing the informed consent document.
Exclusion criteria
* History of previous infection with hookworm. * Prior extensive and continuous travel, work, or residence (\> 1 month) in a hookworm-endemic region. * Pregnancy as determined by a positive urine hCG test (if female). * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history or physical examination. * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol. * Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol. * Participation in an investigational vaccine or drug trial within 14 days of starting this study. * Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. * History of a severe allergic reaction or anaphylaxis. * Known immunodeficiency syndrome. * Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study. * History of a surgical splenectomy. * Extensive dermatitis precluding skin testing * Current use of a beta blocker (oral or topical) or anti-histamine medication. A volunteer may participate in the study if they agree to withhold use of an anti-histamine for at least 5 days prior to application of the skin test. * Use of a tricyclic anti-depressant within the past month.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 100 Mcg/ml Na-ASP-2 Prick-puncture Skin Test | 15 minutes after skin test application | Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1000 Mcg/ml Na-ASP-2 Prick-puncture Skin Test | 15 minutes after skin test application | Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control |
| 100 Mcg/ml Na-ASP-2 Intradermal Skin Test | 15 minutes after skin test application | Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control |
| 1000 Mcg/ml Na-ASP-2 Intradermal Skin Test | 15 minutes after skin test application | Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between March and May 2008, primarily by means of advertising the study in and around The George Washington University, where the study site is located.
Participants by arm
| Arm | Count |
|---|---|
| Na-ASP-2 Hookworm Antigen Skin Test All participants will have the same number of concentrations of the Na-ASP-2 skin test reagent applied to their arms, using both the prick-puncture and intradermal techniques. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Na-ASP-2 Hookworm Antigen Skin Test |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
100 Mcg/ml Na-ASP-2 Prick-puncture Skin Test
Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control
Time frame: 15 minutes after skin test application
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Na-ASP-2 Hookworm Antigen Skin Test | 100 Mcg/ml Na-ASP-2 Prick-puncture Skin Test | 0 Units on a scale |
Secondary
1000 Mcg/ml Na-ASP-2 Intradermal Skin Test
Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control
Time frame: 15 minutes after skin test application
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Na-ASP-2 Hookworm Antigen Skin Test | 1000 Mcg/ml Na-ASP-2 Intradermal Skin Test | 1.25 units on a scale |
Secondary
1000 Mcg/ml Na-ASP-2 Prick-puncture Skin Test
Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control
Time frame: 15 minutes after skin test application
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Na-ASP-2 Hookworm Antigen Skin Test | 1000 Mcg/ml Na-ASP-2 Prick-puncture Skin Test | 0.21 units on a scale |
Secondary
100 Mcg/ml Na-ASP-2 Intradermal Skin Test
Mean grade of wheal reaction after 2 applications of the skin test reagent per participant. For each skin test reaction, the grade of the test was determined based on the mean of the longest and orthogonal diameters, which was then compared to the equivalent measurements of a histamine solution positive control that was applied at the same time as the test. Grading was as follows: 0 no discernible wheal 1. \< ½ histamine diameter 2. ≥ ½ histamine; \< histamine diameter 3. = size of histamine control ± 1 mm 4. \> histamine diameter; \< 2x diameter 5. ≥ 2x histamine control
Time frame: 15 minutes after skin test application
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Na-ASP-2 Hookworm Antigen Skin Test | 100 Mcg/ml Na-ASP-2 Intradermal Skin Test | 0.17 units on a scale |