Immune Interactions in Severe Asthma

Asthma Clinical Trial

Official title:

Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02566668
• Other study ID #: PRO15050456
• Status: Active, not recruiting
• Start date: September 2015
• Est. completion date: March 2028

Study information

• Verified date: January 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: March 2028
• Est. primary completion date: March 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Other:
• 1 year Observational Follow-up
Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.

Locations

Country	Name	City	State
United States	University of Pittsburgh Asthma Institute at UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

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