Clinical trial NCT02230189: Study of the Inflammation and Airway Changes That Occur After Exposure to Allergen in Asthmatics
Official title: Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Allergen challenge
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2014-09-03
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group before and after administration of allergen
Primary purpose: BASIC_SCIENCE

Brief summary: This protocol describes a single site mechanistic study to investigate microRNAs (miRNAs) that are differentially expressed in the airway epithelium of patients with asthma at baseline and in response to allergen challenge. We hypothesize that allergen exposure enhances airway smooth muscle contractility and epithelial cell mRNA/miRNA production as a consequence of locally increased T-cell derived cytokine production. The study will involve three visits over the course of approximately 14 days. At Visit 1, participants will be characterized in detail with lung function testing, methacholine challenge testing, and allergen skin prick testing. At Visit 2, participants will undergo bronchoscopy with segmental allergen administration of either cat or dust mite standardized allergen extract. At Visit 3 (either 24 hours later or 7 days later), bronchoscopy will be performed to collect airway samples including bronchoalveolar lavage (BAL), epithelial brushings and endobronchial biopsies. Sample analysis will include measurement of miRNA and mRNA expression in epithelial brushings (RNAseq and qPCR); analysis of cell surface markers on BAL cells and blood cells; and collection of endobronchial biopsies for immunostaining of immune cells localization, immunoblotting of smooth cell protein phosphorylation, analysis of mucin content and smooth muscle cell subculture. A total of 38 subjects (26 asthmatics with stable or well-controlled asthma, 6 allergic non-asthmatics and 6 non-allergic non-asthmatics) will complete the study.


Eligibility criteria: Allergic/Non-Asthmatic subjects and Allergic/Asthmatic subjects

Inclusion Criteria:

* Positive skin test to dust mite or cat allergen

Non-Allergic/Non-Asthmatic subjects

Inclusion Criteria:

* Negative skin test to panel of 12 allergens, including dust mite and cat allergen

All groups

Exclusion Criteria:

* History of intubation for asthma exacerbation
* Use of Xolair (omalizumab) within the last 6 months
* Immunotherapy with cat or dust mite extract now or in the past 5 years
* ≥ 10 pack-years smoking or any smoking in the past year
* Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection
* History of dermatographia
* History of anaphylaxis to cat allergen
* Participation in another research study involving a drug or biologic during the past 30 days
* Presence of past or current medical problems/other factors that may pose additional risks from participation or influence study results, as determined per study investigator

Primary outcomes:
measure: Difference in Expression of Epithelial miRNAs (in Read Counts) 24 Hours After Allergen-challenge as Compared to 24 Hours After Diluent Challenge in Participants With Allergic Asthma
timeFrame: 24 hours
measure: Difference in Expression of Epithelial miRNAs (in Read Counts) 7 Days After Allergen-challenge as Compared to 7 Days After Diluent Challenge
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Prescott G Woodruff, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: