Identification of Allergic Asthmatics Reactive to Felis Catus (Cat Hair) Allergen Inhalation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03780387|
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : April 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Asthma Atopic||Biological: Felis Catus||Early Phase 1|
Asthma is an increasingly common chronic illness among children and adults, and allergen exposure is among the most common triggers for asthma exacerbations. Exacerbations of allergic asthma are characterized by an early phase response (EPR), mediated by release of preformed mediators like histamine from mast cells, and a late phase response (LPR) 3-7 hours later mediated by chemokines and cytokines that attract leukocytes such as neutrophils and eosinophils to the airways, increase mucus production, trigger airway smooth muscle contraction, and result in airway constriction and airway hyperreactivity (AHR). The LPR does not occur in the absence of an EPR. The LPR is thought to be predominantly responsible for the symptoms associated with acute exacerbations of allergic asthma and is often used as the measure of efficacy in trials of asthma therapeutics.
This group has taken a particular interest in targeting an inflammatory cytokine, Interleukin-1β, involved in both the early and late phase asthmatic responses to inhaled allergen in allergic asthmatics. In the lung, interleukin 1 beta (IL-1β) is produced by numerous cell types (including epithelial cells, macrophages, neutrophils, eosinophils, and mast cells), where it signals through its receptor to induce transcription of pro-inflammatory genes (17-19). IL-1β is increased in bronchoalveolar lavage fluid from persons with symptomatic asthma vs. those with asymptomatic asthma; likewise, immunohistochemistry of bronchial biopsies of allergic asthmatics reveal increased expression of IL-1β in both bronchial epithelial cells and macrophages.
In order to better understand the role of IL-1β in allergen-induced airway inflammation, induced sputum will be obtained to determine if higher baseline sputum IL-1β concentrations or larger increases in IL-1β following allergen challenge impact non-specific airway hyperresponsiveness (via methacholine challenge), sputum granulocyte recruitment (neutrophil and eosinophil counts and exhaled nitric oxide (eNO), a marker of airway eosinophilia), or changes in expression of inflammatory or allergy-related genes. To this last point, little is known about the mechanisms contributing to response patterns in allergic asthmatics undergoing allergen challenge. Changes in gene expression occurring during the window of time between the EPR and LPR, as these expression changes may dictate whether or not a LPR occurs or to what extent it occurs.
The goal of this screening protocol is to identify subjects who exhibit both an EPR and LPR and who will be eligible for enrollment in the yet to be developed IL-1β protocols. Subjects will undergo a baseline methacholine challenge to establish reactivity, then allergen exposure, followed 24 hours later by methacholine challenge.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Identification of Allergic Asthmatics Reactive to Felis Catus (Cat Hair) Allergen Inhalation|
|Actual Study Start Date :||April 16, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Inhaled Allergen Challenge
Felis Catus sensitive, mild asthmatics will undergo inhaled allergen challenge.
Biological: Felis Catus
Inhalation of Felis Catus allergen in subjects allergic to Felis Catus
- Decline in Forced Expiratory Volume in 1 second (FEV1) ≥15% during the late phase response [ Time Frame: Pre-inhalation challenge and 3-10 hours after inhalation challenge ]Participants will undergo an inhaled allergen challenge to identify those with a measurable late phase response (LPR) to inhaled Felis Catus allergen extract. Baseline FEV1 will be measured prior to administration of the allergen challenge. The presence of an LPR will be defined as a decline in FEV1 of ≥15% from baseline values 3-10 hours after the onset of the early phase response (which typically occurs within 30 minutes of allergen challenge).
- Levels of IL-1β in induced sputum [ Time Frame: Baseline and 24 hours post- inhalation challenge ]Participants will undergo a hypertonic saline induced sputum procedure at baseline (within ~2 weeks of the allergen challenge), and again at 24 hours following inhaled allergen challenge. IL-1β concentrations in the sputum will be determined via ELISA. In addition to assessing changes in IL-1β levels, we will determine if IL-1β levels are predictive of key asthma outcomes following inhaled allergen challenge (see outcomes 3-7).
- Sputum granulocytes [ Time Frame: Baseline and 24 hours post- inhalation challenge ]Cellularity of sputum obtained at baseline and again at 24 hours following inhaled allergen challenge will be assessed.
- Mucins in sputum [ Time Frame: Baseline and 24 hours post- inhalation challenge ]Sputum mucins will be measured at baseline, and again at 24 hours following inhaled allergen challenge
- Maximum drop in FEV1 during the late phase response per participant [ Time Frame: Pre-inhalation challenge and 3-10 hours after inhalation challenge ]FEV1 will be measured prior to administration of the inhaled allergen challenge. The maximum drop in FEV1 that occurs during the late phase (3-10 hours after challenge) will be determined.
- Airway hyper-responsiveness [ Time Frame: Baseline and 24 hours post- inhalation challenge ]Participants will undergo a methacholine challenge to assess airway hyper-responsiveness at baseline. Changes in methacholine reactivity from baseline to 24 hours after inhaled allergen challenge will be determined.
- Exhaled nitric oxide (eNO) levels in ppb [ Time Frame: Baseline and 24 hours post- inhalation challenge ]eNO levels will be measured at baseline, and 24 hours after inhaled allergen challenge.
- Heart Rate Variability (HRV) [ Time Frame: Pre challenge and immediately post challenge ]HRV with Spacelabs technology will be measured 24 hours pre and during inhalation challenge
- Nasal Epithelial Lining Fluid (Nasal ELF) [ Time Frame: Pre challenge and immediately post challenge ]Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta, TNF alpha
- Nasal Epithelial Lining Fluid (Nasal ELF) [ Time Frame: Pre challenge and 7 hours post challenge ]Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta, TNF alpha
- Nasal Epithelial Lining Fluid (Nasal ELF) [ Time Frame: Pre challenge and 24 hours post challenge ]Nasal strip to collect cytokine IL-8, IL-6, IL-1alpha, IL-1 beta, TNF alpha
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03780387
|Contact: Martha Almondemail@example.com|
|United States, North Carolina|
|UNC Center for Environmental Medicine, Asthma and Lung Biology||Recruiting|
|Chapel Hill, North Carolina, United States, 27599-7310|
|Contact: Brian Ring, BS 919-843-8472 firstname.lastname@example.org|
|Principal Investigator: Michelle Hernandez, MD|
|Principal Investigator:||Michelle Hernandez, MD||University of North Carolina, Chapel Hill|