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

• ClinicalTrials.gov Identifier: NCT02230189
• Recruitment Status: Completed
• First Posted: September 3, 2014
• Last Update Posted: January 31, 2022
• Sponsor: Prescott Woodruff
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Prescott Woodruff, University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Biological: Segmental airway allergen challenge; Procedure: Bronchoscopy; Diagnostic Test: Methacholine challenge test; Diagnostic Test: Spirometry; Diagnostic Test: Allergen skin prick test	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single group before and after administration of allergen
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: January 2020
• Actual Study Completion Date: January 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Allergen challenge subjects; 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)	Biological: Segmental airway allergen challenge; Procedure: Bronchoscopy; Diagnostic Test: Methacholine challenge test; Diagnostic Test: Spirometry; Diagnostic Test: Allergen skin prick test

Outcome Measures

Primary Outcome Measures :

1. Difference in expression of epithelial miRNAs (in read counts) after allergen-challenge as compared to after diluent challenge [ Time Frame: 24 hours or 7 days ]
   After processing of the sequencing data to read counts, the difference in read count in the allergen challenged as compared to the diluent challenged segment at the given follow-up time point will be calculated for each subject. The change in read count for each miRNA in the allergen samples will be compared to the change in read count in the diluent samples and statistical significance will be assessed using the Benjamini Hochberg false discovery rate method (FDR) to account for multiple comparisons.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

Sponsors and Collaborators

Prescott Woodruff

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Prescott G Woodruff, MD, MPH; University of California, San Francisco

More Information

Additional Information:

UCSF Airway Clinical Research Center 

• Responsible Party: Prescott Woodruff, Professor of Medicine, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02230189
• Other Study ID Numbers: 14-14224; 5U19AI077439 ( U.S. NIH Grant/Contract )
• First Posted: September 3, 2014
• Last Update Posted: January 31, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prescott Woodruff, University of California, San Francisco:

Asthma; Allergen challenge

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Methacholine Chloride; Miotics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Parasympathomimetics; Bronchoconstrictor Agents; Respiratory System Agents; Muscarinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action