Role of microRNAs in T Cell-Driven Inflammation in Asthma (RITA)
This will be a single center study of asthmatic subjects and healthy controls which will investigate mechanisms of asthma through detailed molecular analysis of airway tissues and fluids. The primary goal will be investigate the role of microRNAs in Th2-driven inflammation in asthma. The investigators hypothesize that asthma is associated with abnormal expression of miRNAs in T cells which favors differentiation into Th2-cells. The investigators further hypothesize that asthma is heterogeneous based on the presence and absence of Th2-driven inflammation and that abnormalities in T cell miRNA expression will be most prominent in a subgroup with high levels of Th2-driven inflammation (as assessed using molecular markers that the investigators have previously established). Finally, the investigators hypothesize that inhaled corticosteroids will normalize the T-cell miRNA abnormalities observed in asthma, as corticosteroids treat Th2-driven inflammation. The samples collected will also facilitate the pursuit of secondary analyses designed to investigate mechanisms of inflammation and remodeling in asthma as well as molecular phenotypes of asthma.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Role of miRNAs in Th2-driven Inflammation in Asthma|
- Change from baseline of T cell miRNA expression at 1 week [ Time Frame: 1 week ] [ Designated as safety issue: No ]Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. We will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05.
- Change from baseline of T cell miRNA expression at 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Identification of T cell miRNAs which normalized by 8 weeks of treatment with inhaled corticosteroids in asthma (as compared to an untreated group). We will measure the same miRNAs by qPCR as identified in the other Primary Outcome (1 week time frame) and define normalization by treatment as a significant difference between change from 0 to 8 weeks in the corticosteroid treated group as compared to the untreated group (false discovery rate <0.05).
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
No Intervention: Healthy non-asthmatic controls
Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.
Active Comparator: Asthmatics (treatment)
Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids.
Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Other Name: Pulmicort
No Intervention: Asthmatics (no treatment)
Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01484691
|Contact: Christine P Nguyen, BSemail@example.com|
|Contact: Bobby J Antalek, MS, MPHfirstname.lastname@example.org|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Principal Investigator:||Prescott G Woodruff, MD, MPH||University of California, San Francisco|