Role of microRNAs in T Cell-Driven Inflammation in Asthma (RITA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of California, San Francisco
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Prescott Woodruff, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01484691
First received: October 26, 2011
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Asthma
Drug: Budesonide

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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).


Estimated Enrollment: 50
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)
Arms Assigned Interventions
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.
Drug: Budesonide
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01484691

Contacts
Contact: Christine P Nguyen, BS 415-476-3824 christine.nguyen@ucsf.edu
Contact: Bobby J Antalek, MS, MPH 415-502-2892 bobby.antalek@ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Prescott G Woodruff, MD, MPH University of California, San Francisco
  More Information

No publications provided

Responsible Party: Prescott Woodruff, Associate Professor of Medicine, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01484691     History of Changes
Other Study ID Numbers: 11-07039
Study First Received: October 26, 2011
Last Updated: April 14, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Budesonide
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 28, 2014