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NCT Number: NCT06270576

Nasal Inflammation Following Endotoxin Challenge in Patients With Asthma

A phase I clinical research study aimed at determining mechanisms that regulate airway mucosal inflammation in asthma endotypes using intranasal administration of endotoxin (lipopolysaccharide from E. coli) in healthy controls and subjects diagnosed with asthma.

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Key information

Conditions

Asthma; Eosinophilic Asthma Bronchial Diseases Eosinophilia Hematologic Diseases Hemic and Lymphatic Diseases Hypereosinophilic Syndrome Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Leukocyte Disorders Lung Diseases Lung Diseases, Obstructive Pulmonary Eosinophilia Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

National Jewish Health

Denver, Colorado, 80206, United States

Location contact

Olivia M VerBurg, BA

CONTACT

303-398-1201

William J Janssen, MD

CONTACT

303-398-1366

William J Janssen, MD

PRINCIPAL_INVESTIGATOR

About this study

Patients with severe asthma can be broadly classified into three endotypes (T2, T1, and T17) based on inflammatory cell and cytokine profiles. Within these endotypes, many patients have high levels of neutrophils in the airways and mucosal epithelium. Our preliminary data suggest that neutrophils in the airways and blood of patients with severe asthma are heterogenous and that subsets exist. The nature of these subsets appears to differ between T2, T1, and T17 asthma endotypes.

In order to advance the field and determine the mechanisms that underpin severe neutrophilic asthma, investigators plan to longitudinally assess transcriptional profiles and functional properties of neutrophil subsets that migrate to the nasal cavity following exposure to a standardized dose of Clinical Reference Center endotoxin (IRB#HS-3131-528, IND 018580).

Investigators will recruit 15 subjects of each asthma endotype (45 total participants with asthma) and 15 healthy controls. LPS will be used to elicit migration of neutrophils into the nasal cavities. Neutrophils will be isolated from the nasal cavities using both nasal lavage and nasal brushes 20 minutes, 1 day and 3 days after endotoxin challenge. Neutrophil biology will be assessed using single-cell RNAseq and ex vivo functional assays.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Participants will have asthma diagnosed by a health care provider. Healthy controls are individuals without asthma.
  • Written informed consent

Exclusion criteria

  • Current or recent illness (in the past 4 weeks)
  • Recent asthma exacerbation (past 4 weeks)
  • History of nasal perforation or nasal surgery
  • Nasal polyposis
  • Presence or prior history of cardiac or systemic disease
  • Bleeding disorder, use of systemic anticoagulants, or antiplatelet therapy
  • Immunocompromised state (HIV, immunoglobulin deficiency, systemic immunosuppressants excluding corticosteroids)
  • Use of tobacco or marijuana in the past 2 months or greater than a 10 pack-year smoking history
  • Currently pregnant or breastfeeding

Treatment and study plan

Lipopolysaccharides

Drug

LPS aka endotoxin is a component of bacterial cell walls and is ubiquitous in the environment. It is found in pet dander, house dust and environmental dusts and has been heavily studied in asthma.

Other names: Endotoxin, LPS, Clinical reference center lipopolysaccharide, LPS E. Coli O:113

Primary outcomes

  1. Neutrophil heterogeneity using single cell RNA sequencing

    Time frame: We anticipate that the study will run over 5 years

    Neutrophil subset composition as determined by single cell RNAseq is compared to endotype groups using a multivariate linear regression framework for compositional data, employing the additive log ratio transformation. Models will include indicator variables for whether a sample is T1 high, T2 high, T17 high or non-asthmatic and will control for age, sex, and smoking status. AM subset gene expression matrices from scRNAseq will be compared between endotypes using the pseudo bulk approach to account for clustering of cells within subjects. To identify global gene expression programs underlying each endotype, bulk RNAseq gene expression data will be normalized using DESeq2's variance stabilizing transformation and similarly compared between endotypes using linear regression models. A Benjamini-Hochberg adjustment will be used to control the false discovery rate.

Sponsors and collaborators

Lead sponsor

National Jewish Health

Other

Registry information

Official study title

Nasal Endotoxin Challenge to Study Mucosal Inflammation in Patients With Asthma

Acronym: Nasal-LPS

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Feb 21, 2024
Registry last updated
Feb 21, 2024

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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