Role of microRNAs in T Cell-Driven Inflammation in Asthma

Asthma Clinical Trial

— RITA  

Official title:

Role of miRNAs in Th2-driven Inflammation in Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01484691
• Other study ID #: 11-07039
• Status: Completed
• Phase: N/A
• Start date: January 2012
• Est. completion date: July 2015

Study information

• Verified date: June 2022
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Group A:

Inclusion Criteria:

• Male and female subjects between the ages of 18 and 70 years

Group B:

Inclusion Criteria:

• Male and female subjects between the ages of 18 and 70 years

• History of asthma

• No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks

• Hyperreactivity to methacholine (PC20FEV1 Methacholine = 8.0 mg/mL)

• At least one of the following symptoms, beta agonist use, or FEV1 criteria:

• Asthma symptoms on at least two days per week; OR

• Beta agonist use on at least two days per week; OR

• FEV1 < 85% predicted

Groups A & B:

Exclusion Criteria:

• Current smokers (smoking within the last 12 months) or former smokers who have a total pack-year smoking history greater than 10

• Pregnant women

• Subjects with a history of lung disease other than asthma

• Subjects with a history of a medical disease, which in the opinion of the investigator may put the subject at extra risk from study-related procedures or because the disease may influence the results of the study

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• Budesonide
Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls	Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators 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. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011.	Baseline (cross-sectional analysis)
Primary	Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment	Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05).	8 weeks after randomization to inhaled corticosteroids or no treatment

External Links

•   UCSF Airway Clinical Research Center