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Immune Interactions in Severe Asthma

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ClinicalTrials.gov Identifier: NCT02566668
Recruitment Status : Recruiting
First Posted : October 2, 2015
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
Sally E. Wenzel MD, University of Pittsburgh

Study Description
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Brief Summary:
This research study is being done to learn more about severe asthma by comparing people with severe asthma to those with milder forms of asthma and people without asthma, at baseline and over time. Individuals are being asked to join a research study to help understand the differences in the lungs and blood of participants with severe asthma compared to those with milder asthma and healthy individuals, as well as differences in overall health. Investigators also want to determine whether these differences predict asthma-related and biologic outcomes over 1 year of follow up.

Condition or disease Intervention/treatment
Asthma Other: 1 year Observational Follow-up

Detailed Description:
This study will obtain human lung samples by bronchoscopy from a range of asthmatics and healthy controls to address questions related to the mechanisms for the development of the complex immune processes observed in the lungs. Samples will be evaluated for Type-1, Type-2 and Interleukin-27 (IL-27) expression (and their downstream signatures). In addition, these samples will be evaluated for the presence or absence of Interleukin-10 (IL-10) as a counter regulatory pathway. These pathways will be directly evaluated in epithelial brushings and bronchoalveolar lavage (BAL) cells, as well as BAL fluid. Broad gene expression profiling (Ribonucleic acid (RNA)-sequencing) will also be performed to determine the range of immune-inflammatory markers present in these severe asthmatics. Investigators will specifically address the Signal Transducers and Activators of Transcription (STAT) signaling pathways, particularly STAT-1 and STAT-3 to determine the pattern of activation and downstream responses to develop new therapies. Additionally, in a subset, investigators will compare targeted and untargeted gene expression as obtained from bronchoscopic samples with expression obtained from clinically performed video assisted thoracoscopic (VATS) biopsies of very severe systemic corticosteroid dependent patients. The ultimate goal of this studies is to determine whether a predictive biomarker panel can be identified in the less invasive bronchoscopic samples which predict the findings seen on VATS biopsy.
Study Design
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Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma
Actual Study Start Date : September 2015
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Groups and Cohorts
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Group/Cohort Intervention/treatment
Asthmatic
1 year observational follow-up
 Other: 1 year Observational Follow-up
Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.
Non-Asthmatic
1 year observational follow-up
 Other: 1 year Observational Follow-up
Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.


Outcome Measures
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Primary Outcome Measures :
  1. Eotaxin-3 and IL-27 expression and their downstream signatures [ Time Frame: 1 Year ]
    Measure eotaxin-3 and IL-27 expression in bronchoalveolar lavage cells and epithelial cells.


Secondary Outcome Measures :
  1. Global gene expression in the airway epithelium and bronchoalveolar lavage cells using RNA-sequencing [ Time Frame: 1 Year ]
  2. Signal transducer and activator of transcription (STAT) signaling pathways [ Time Frame: 1 Year ]
    Pattern of activation and downstream responses

  3. Targeted and untargeted gene expression as obtained from bronchoscopic samples [ Time Frame: 1 Year ]
    Compare with expression obtained from video assisted thoracoscopic (VATS) biopsies of systemic corticosteroid dependent patients.


Biospecimen Retention:   Samples With DNA
Blood - total and specific Immunoglobulin E (IgE); complete blood count; plasma and serum; Deoxyribonucleic Acid (DNA); peripheral blood mononuclear cells (PBMC) Endobronchial biopsy Endobronchial brushings Pulmonary Lavage Exhaled Breath Condensate (EBC)

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects will be selected using a Research Registry and clinic patients of the Investigators.
Criteria

Inclusion Criteria:

  • 18-65 years of age
  • Non-smoker
  • Asthmatic subjects must also demonstrate forced expiratory volume in 1 second (FEV1) bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a methacholine provocative concentration causing a 20% fall in FEV1 (PC20) ≤16 mg/mL (Historical methacholine data from previous National Institutes of Health (NIH) trial will be allowed)

Exclusion Criteria:

  • Greater than 10 pack year smoking history (none in the last year)
  • Vocal cord dysfunction, cystic fibrosis or chronic obstructive pulmonary disorder
  • Other lung disease, or any coronary artery disease, hypertension, diabetes or renal failure that is not well-controlled.

Healthy Controls only: Pre-bronchodilator FEV1/Forced vital capacity (FVC) <0.70 or an improvement in FEV1 of more than 12% following 4 puffs of albuterol.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02566668


Contacts
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Contact: Renee Wunderley 412-864-2218 Wunderleyr@upmc.edu

Locations
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United States, Pennsylvania
University of Pittsburgh Asthma Institute at UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Renee Wunderley    412-864-2218    Wunderleyr@upmc.edu   
Sponsors and Collaborators
University of Pittsburgh
Investigators
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Principal Investigator: Sally E Wenzel, MD University of Pittsburgh
More Information
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Responsible Party: Sally E. Wenzel MD, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02566668    
Other Study ID Numbers: PRO15050456
First Posted: October 2, 2015    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Keywords provided by Sally E. Wenzel MD, University of Pittsburgh:
Asthma
Severe Asthma
IL-10
IL-27
 IL-13
Epithelial Cells
T lymphocytes
Interferon-g
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
 Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases