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

NCT02230189 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14-142245U19AI077439
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Asthma; Allergen challenge

Outcome Measures

Primary Outcomes (2)

• 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

  For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 24 hours later. After processing brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(\<0.05). The direction of change does not have clinical significance; this was a mechanistic study.

  24 hours

• Difference in Expression of Epithelial miRNAs (in Read Counts) 7 Days After Allergen-challenge as Compared to 7 Days After Diluent Challenge

  For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 7 days later. After processing the brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(\<0.05). The direction of change does not have clinical significance; this was a mechanistic study.

  7 days

Study Arms (1)

Allergen challenge subjects

EXPERIMENTAL

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

Interventions

Segmental airway allergen challenge BIOLOGICAL

Allergen challenge subjects

Bronchoscopy PROCEDURE

Allergen challenge subjects

Methacholine challenge test DIAGNOSTIC_TEST

Allergen challenge subjects

Spirometry DIAGNOSTIC_TEST

Allergen challenge subjects

Allergen skin prick test DIAGNOSTIC_TEST

Allergen challenge subjects

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Positive skin test to dust mite or cat allergen
• Non-Allergic/Non-Asthmatic subjects
• Negative skin test to panel of 12 allergens, including dust mite and cat allergen
• All groups

You may not qualify if:

• 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

Sponsors & Collaborators

• Prescott Woodruff: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Links

• UCSF Airway Clinical Research Center

MeSH Terms

Conditions

Asthma

Interventions

Bronchoscopy; Spirometry

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Respiratory Function Tests

Results Point of Contact

• Title: PI: Prescott G. Woodruff, MD, MPH
• Organization: University of California, San Francisco

prescott.woodruff@ucsf.edu

415-514-2061

Study Officials

• Prescott G Woodruff, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Single group before and after administration of allergen

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 3, 2014
• Study Start: March 1, 2015
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: August 16, 2022
• Results First Posted: August 16, 2022

Record last verified: 2022-07

Locations

US (1)