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A drug (mepolizumab) that reduces allergic inflammation will affect the function of allergy cells called eosinophils which are produced by the body in response to allergen exposure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mepolizumab | Experimental | up to 3 monthly doses of 750mg i.v. mepolizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mepolizumab | Biological | up to three monthly doses of 750mg i.v. mepolizumab |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Primary Endpoint of the Study is the Percent of Eosinophils in the Bronchoalveolar Lavage Fluid After Segmental Allergen Challenge, Before and After Mepolizumab Administration (Bronchoscopy #2 vs. Bronchoscopy #4). | Percent of eosinophils was determined in the bronchoalveolar lavage fluid collected from the participant after segmental allergen challenge. This was done via differential cell count using Hema-3 stain. Cell differentials were determined by counting a total of 1000 cells on two cytospin preparations. The percent eosinophils were done before and after administration of mepolizumab for a specified amount of time (up to 3 months of administration). | before and after up to 3 months of Mepo. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab | IL-5 was measured via ELISA on bronchoalveolar lavage fluid before and after mepolizumab administration (up to 3 months of administration). Fluid was prepared in LowCross-Buffer to minimize potential matrix effects. A 1/2 dilution of 1X bronchoalveolar fluid was used for IL-5 detection. Data are expressed as pg/mL and are extrapolated to 1X. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nizar N Jarjour, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin- Madison | Madison | Wisconsin | 53792-9988 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28862877 | Derived | Kelly EA, Esnault S, Liu LY, Evans MD, Johansson MW, Mathur S, Mosher DF, Denlinger LC, Jarjour NN. Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1385-1395. doi: 10.1164/rccm.201611-2234OC. |
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After a participant signs a consent form, he/she goes through an extensive screening process that includes 4 research visits to the clinic before being assigned to their treatment. The inclusion/exclusion criteria for this study was long and many subjects screen failed prior to being assigned to a treatment.
The recruitment period lasted two years (July 2008 through November 2010. Participants were recruited from our Recruitment Database, through local advertisements and the local allergy/asthma clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Mepolizumab | up to 3 monthly doses of 750mg i.v. mepolizumab mepolizumab: up to three monthly doses of 750mg i.v. mepolizumab |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Mepolizumab | up to 3 monthly doses of 750mg i.v. mepolizumab mepolizumab: up to three monthly doses of 750mg i.v. mepolizumab |
| 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 | The Primary Endpoint of the Study is the Percent of Eosinophils in the Bronchoalveolar Lavage Fluid After Segmental Allergen Challenge, Before and After Mepolizumab Administration (Bronchoscopy #2 vs. Bronchoscopy #4). | Percent of eosinophils was determined in the bronchoalveolar lavage fluid collected from the participant after segmental allergen challenge. This was done via differential cell count using Hema-3 stain. Cell differentials were determined by counting a total of 1000 cells on two cytospin preparations. The percent eosinophils were done before and after administration of mepolizumab for a specified amount of time (up to 3 months of administration). | Participants had mild allergic asthma with a positive skin-prick test to house dust mite, ragweed, or a standardized extract of cat, a pre-180 4g albuterol FEV1 ≥70%, a post-albuterol FEV1 ≥ 80%; airway reversibility to albuterol (180 4g) ≥12% and/or airway hyper-reactivity to methacholine (PC20 ≤8 mg/ml). | Posted | Median | Inter-Quartile Range | percent of bronchoalveolar eosinophils | before and after up to 3 months of Mepo. |
|
Each participant was followed anywhere between 36 weeks to 45 weeks depending on treatment path.
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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 | Mepolizumab | up to 3 monthly doses of 750mg i.v. mepolizumab mepolizumab: up to three monthly doses of 750mg i.v. mepolizumab |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Laryngitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
Our small sample size limits any meaningful consideration about the mechanisms of mepolizumab's clinical action. The prolonged time commitment and inclusion of four bronchoscopies affected subject retention and limited the sample size.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gina Crisafi, BS | UW Madison | 608-265-4554 | gmc@medicine.wisc.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C434107 | mepolizumab |
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| before and after up to 3 months of Mepo |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| OG000 | Mepolizumab | up to 3 monthly doses of 750mg i.v. mepolizumab mepolizumab: up to three monthly doses of 750mg i.v. mepolizumab |
|
|
|
| Secondary | Effect of Mepolizumab on Bronchoalveolar Lavage Fluid Concentrations of IL-5 Cytokine Before and After Mepolizumab | IL-5 was measured via ELISA on bronchoalveolar lavage fluid before and after mepolizumab administration (up to 3 months of administration). Fluid was prepared in LowCross-Buffer to minimize potential matrix effects. A 1/2 dilution of 1X bronchoalveolar fluid was used for IL-5 detection. Data are expressed as pg/mL and are extrapolated to 1X. | Participants had mild allergic asthma with a positive skin-prick test to house dust mite, ragweed, or a standardized extract of cat, a pre-180 4g albuterol FEV1 ≥70%, a post-albuterol FEV1 ≥ 80%; airway reversibility to albuterol (180 4g) ≥12% and/or airway hyper-reactivity to methacholine (PC20 ≤8 mg/ml). | Posted | Median | Inter-Quartile Range | pg/ml | before and after up to 3 months of Mepo |
|
|
|
|
| 0 |
| 38 |
| 0 |
| 38 |
| 8 |
| 38 |
| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Common cold |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Back pain after a bike race |
|
| Erythema | Immune system disorders | Non-systematic Assessment | Erythema at IV site |
|
| Pain | General disorders | Non-systematic Assessment | Pain at IV site |
|
| Rash on neck | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Rash on neck 9 days after previous research visit - related to switching soap. |
|
| Fever | General disorders | Non-systematic Assessment | Fever of 101.1F post bronchoscopy |
|
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |