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The overarching hypothesis of this proposal is that IL-5 acts on multiple sinus tissue cell types, including plasma cells and epithelial cells, to promote immune dysregulation, and that inhibition of IL-5 affects several relevant effector pathways that lead to clinical benefit.
Further characterization of the role of IL-5Rα expression and function on human plasma cells will determine whether inhibiting IL-5 signaling on these cells offers therapeutic promise in other diseases related to plasma cell proliferation. Further characterization of human upper airway epithelial cell IL-5Rα expression and function will determine whether or not inhibiting IL-5 signaling on these cells offers therapeutic promise in other diseases related to epithelial dysfunction. IL-5Rα expression has been identified on several relevant sinus tissue effector cells, including on nasal polyp plasma cells and epithelial cells, and the aim of this study is to further the field by determining the consequences of IL-5 signaling on those cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aspirin-exacerbated respiratory disease (AERD) | Aspirin-exacerbated respiratory disease (AERD) |
| |
| Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP) | Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP) |
| |
| Healthy controls | Individuals who do not have AERD or CRSwNP |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-Interventional | Other | No intervention. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Nasal Polyp Plasma Cell Transcriptome | We will determine the number of participants from whom a transcriptional profile of nasal polyp plasma cells is analyzable from bulk RNA sequencing of sorted nasal polyp plasma cells. | At baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | We will determine the number of participants from whom a readout of IL-5Ra is analyzable from the plasma cells in their nasal tissue | At baseline |
| Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed |
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Inclusion Criteria:
Exclusion Criteria:
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AERD, CRSwNP, healthy controls undergoing planned elective sinus surgery.
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| Name | Affiliation | Role |
|---|---|---|
| Tanya Laidlaw | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Aspirin-exacerbated Respiratory Disease (AERD) | Aspirin-exacerbated respiratory disease (AERD) Non-Interventional: No intervention. |
| FG001 | Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP) Non-Interventional: No intervention. |
| FG002 | Healthy Controls | Individuals who do not have AERD or CRSwNP Non-Interventional: No intervention. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Aspirin-exacerbated Respiratory Disease (AERD) | Aspirin-exacerbated respiratory disease (AERD) Non-Interventional: No intervention. |
| BG001 | Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Participants With Nasal Polyp Plasma Cell Transcriptome | We will determine the number of participants from whom a transcriptional profile of nasal polyp plasma cells is analyzable from bulk RNA sequencing of sorted nasal polyp plasma cells. | Posted | Count of Participants | Participants | At baseline |
|
At the single visit at which samples were collected. This was a single-visit sample-collection observational study. No intervention.
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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 | Aspirin-exacerbated Respiratory Disease (AERD) | Aspirin-exacerbated respiratory disease (AERD) Non-Interventional: No intervention. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tanya M. Laidlaw, MD, Associate Professor of Medicine | Brigham and Women's Hospital, Allergy and Clinical Immunology | 6177329850 | tlaidlaw@partners.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 18, 2023 | Dec 18, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009298 | Nasal Polyps |
| ID | Term |
|---|---|
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D011127 | Polyps |
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We will determine the number of participants from whom IL-5-elicited signaling on their nasal epithelial tissue can be analyzed. |
| At baseline |
Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP)
Non-Interventional: No intervention.
| BG002 | Healthy Controls | Individuals who do not have AERD or CRSwNP Non-Interventional: No intervention. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Healthy Controls | Individuals who do not have AERD or CRSwNP Non-Interventional: No intervention. |
|
|
| Secondary | Number of Participants With Functional Readouts of IL-5Ra on Nasal Polyp Plasma Cells. | We will determine the number of participants from whom a readout of IL-5Ra is analyzable from the plasma cells in their nasal tissue | Posted | Count of Participants | Participants | At baseline |
|
|
|
| Secondary | Number of Patients for Whom IL-5Ra Signaling on Nasal Epithelial Cells Can be Analyzed | We will determine the number of participants from whom IL-5-elicited signaling on their nasal epithelial tissue can be analyzed. | Posted | Count of Participants | Participants | At baseline |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Aspirin-tolerant Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) | Aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP) Non-Interventional: No intervention. | 0 | 10 | 0 | 10 | 0 | 10 |
| EG002 | Healthy Controls | Individuals who do not have AERD or CRSwNP Non-Interventional: No intervention. | 0 | 10 | 0 | 10 | 0 | 10 |
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| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |