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NCT Number: NCT02230189

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

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.

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Key information

Conditions

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

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California, San Francisco

San Francisco, California, 94143, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Segmental airway allergen challenge

Biological

Bronchoscopy

Procedure

Methacholine Challenge Test

Diagnostic Test

Spirometry

Diagnostic Test

Allergen skin prick test

Diagnostic Test

Primary outcomes

  1. 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

    Time frame: 24 hours

    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.

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

    Time frame: 7 days

    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.

Sponsors and collaborators

Lead sponsor

Prescott Woodruff

Other

Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Registry information

Official study title

Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.

Acronym: ACE

Important dates

Study start
2015
Primary completion
2020
Study completion
2020
First posted
Sep 3, 2014
Registry last updated
Aug 16, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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