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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 : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
Sally E. Wenzel MD, University of Pittsburgh

Tracking Information
First Submitted Date September 18, 2015
First Posted Date October 2, 2015
Last Update Posted Date March 30, 2021
Actual Study Start Date September 2015
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 3, 2016)
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.
Original Primary Outcome Measures
 (submitted: September 30, 2015)
Type-1, Type-2 and IL-27 expression and their downstream signatures [ Time Frame: 1 Year ]
Determine the presence or absence of IL-10 as a counter regulatory pathway
Change History
Current Secondary Outcome Measures
 (submitted: November 3, 2016)
  • Global gene expression in the airway epithelium and bronchoalveolar lavage cells using RNA-sequencing [ Time Frame: 1 Year ]
  • Signal transducer and activator of transcription (STAT) signaling pathways [ Time Frame: 1 Year ]
    Pattern of activation and downstream responses
  • 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.
Original Secondary Outcome Measures
 (submitted: September 30, 2015)
  • Broad gene expression profiling (RNA-sequencing) [ Time Frame: 1 Year ]
    Determine the range of immune-inflammatory markers present in the severe asthmatic subjects
  • STAT signaling pathways [ Time Frame: 1 Year ]
    Determine the pattern of activation and downstream responses
  • Targeted and untargeted gene expression [ Time Frame: 1 Year ]
    Determine whether, compared to VATS biopsies of very severe systemic corticosteroid dependent patients, a predictive biomarker panel can be identified in the less invasive bronchoscopic samples
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Immune Interactions in Severe Asthma
Official Title Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma
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.
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 Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
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)
Sampling Method Non-Probability Sample
Study Population Subjects will be selected using a Research Registry and clinic patients of the Investigators.
Condition Asthma
Intervention Other: 1 year Observational Follow-up
Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.
Study Groups/Cohorts
  • Asthmatic
    1 year observational follow-up
    Intervention: Other: 1 year Observational Follow-up
  • Non-Asthmatic
    1 year observational follow-up
    Intervention: Other: 1 year Observational Follow-up
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: September 30, 2015)
120
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 2026
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Eligibility 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.

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Valerie McFarland 412-864-2218 mcfarlandvm@upmc.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02566668
Other Study ID Numbers PRO15050456
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Sally E. Wenzel MD, University of Pittsburgh
Study Sponsor University of Pittsburgh
Collaborators Not Provided
Investigators
Principal Investigator: Sally E Wenzel, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date March 2021