Pittsburgh, Pennsylvania 15213


Purpose:

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.


Study summary:

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.


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.


Study is Available At:


Original ID:

PRO15050456


NCT ID:

NCT02566668


Secondary ID:


Study Acronym:


Brief Title:

Immune Interactions in Severe Asthma


Official Title:

Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma


Overall Status:

Recruiting


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pittsburgh


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Observational


Study Design:


Number of Arms:

0


Number of Groups:

2


Total Enrollment:

120


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Sally E Wenzel, MD
Principal Investigator
University of Pittsburgh
Primary Contact:Renee Wunderley
412-864-2218
Wunderleyr@upmc.edu

Study Dates

Start Date:September 2015
Completion Date:March 2021
Completion Type:Anticipated
Primary Completion Date:March 2020
Primary Completion Type:Anticipated
Verification Date:April 2019
Last Changed Date:April 2, 2019
First Received Date:September 18, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Eotaxin-3 and IL-27 expression and their downstream signatures
Time Frame:1 Year
Safety Issues:False
Description:Measure eotaxin-3 and IL-27 expression in bronchoalveolar lavage cells and epithelial cells.
Outcome Type:Secondary Outcome
Measure:Global gene expression in the airway epithelium and bronchoalveolar lavage cells using RNA-sequencing
Time Frame:1 Year
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Signal transducer and activator of transcription (STAT) signaling pathways
Time Frame:1 Year
Safety Issues:False
Description:Pattern of activation and downstream responses
Outcome Type:Secondary Outcome
Measure:Targeted and untargeted gene expression as obtained from bronchoscopic samples
Time Frame:1 Year
Safety Issues:False
Description:Compare with expression obtained from video assisted thoracoscopic (VATS) biopsies of systemic corticosteroid dependent patients.

Study Interventions

Intervention Type:Other
Name:1 year Observational Follow-up
Description:Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.
Arm Name:Asthmatic

Study Arms

Study Arm Type:Other
Arm Name:Non-Asthmatic
Description:1 year observational follow-up
Study Arm Type:Other
Arm Name:Asthmatic
Description:1 year observational follow-up

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Pittsburgh

Samples and Retentions

Sample 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)
Study Population: Subjects will be selected using a Research Registry and clinic patients of the Investigators.
Sample Method:Non-Probability Sample

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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