Study of the Inflammation and Airway Changes That Occur After Exposure to Allergen in Asthmatics (ACE)

Prescott Woodruff

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Biological: Segmental airway allergen challenge; Procedure: Bronchoscopy; Diagnostic Test: Methacholine challenge test; Diagnostic Test: Allergen skin prick test; Diagnostic Test: Spirometry

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02230189

14-14224

5U19AI077439 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 1 patient group

Allergen challenge subjects

Experimental group

Description:

Intervention: Segmental airway allergen challenge Three types of subjects are studied in this arm: 1) Volunteers with neither asthma nor allergy (as established by skin prick testing); 2) Volunteers with allergy (as established by skin prick testing) but without asthma; and 3) Volunteers with both asthma and allergy (as established by skin prick testing)

Treatment:

Diagnostic Test: Spirometry

Biological: Segmental airway allergen challenge

Diagnostic Test: Methacholine challenge test

Procedure: Bronchoscopy

Diagnostic Test: Allergen skin prick test