Asthma; EosinophilicPhase 1Nasal-LPSNCT06270576
Nasal Inflammation Following Endotoxin Challenge in Patients With Asthma
A Phase 1 study testing Lipopolysaccharides in people with Asthma; Eosinophilic and Asthma, run by National Jewish Health at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Asthma; Eosinophilic, Asthma
- What is being tested?
- Lipopolysaccharides
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2024to Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants will have asthma diagnosed by a health care provider. Healthy controls are individuals without asthma.
- Written informed consent
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Jewish Health
Denver, Colorado, 80206
William J Janssen, MD, 303-398-1366
Olivia M VerBurg, BA, 303-398-1201
About this study
Official title: Nasal Endotoxin Challenge to Study Mucosal Inflammation 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.
Read the detailed description
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.
- Conditions
- Asthma; Eosinophilic, Asthma
- Being tested
- Lipopolysaccharides
- Medical subject headings
- Pulmonary Eosinophilia, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LipopolysaccharidesDrug
Also called Endotoxin, LPS, Clinical reference center lipopolysaccharide, LPS E. Coli O:113
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.
| Study group | Role | What they receive |
|---|---|---|
| Asthma Group | Active comparator | Subjects diagnosed with one of the three asthma endotypes being studied (T2, T1, or T17). Receives: Drug: Lipopolysaccharides |
| Control Group | Active comparator | Subjects with no diagnosis of asthma or other respiratory disease and are deemed healthy. Receives: Drug: Lipopolysaccharides |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil heterogeneity using single cell RNA sequencing
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.
Measured: We anticipate that the study will run over 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2024
- Study startApr 2024 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthma; EosinophilicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Jewish Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Janssen, MD, National Jewish Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06270576
- Sponsor's protocol ID
- HS3131
- Acronym
- Nasal-LPS
- Status last verified
- Feb 2024
- First submitted
- 30 Jan 2024
- Last updated
- 21 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nasal Endotoxin Challenge to Study Mucosal Inflammation in Patients With Asthma
- ClinicalTrials.gov ID
- NCT06270576
- Acronym / sponsor ID
- Nasal-LPS / HS3131
- Conditions
- Asthma; Eosinophilic, Asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Jewish HealthUniversity, hospital or other
- Study start
- Apr 2024 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 21 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asthma Group | Active comparator | Drug: LipopolysaccharidesSubjects diagnosed with one of the three asthma endotypes being studied (T2, T1, or T17). |
| Control Group | Active comparator | Drug: LipopolysaccharidesSubjects with no diagnosis of asthma or other respiratory disease and are deemed healthy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participants will have asthma diagnosed by a health care provider. Healthy controls are individuals without asthma.
- Written informed consent
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LipopolysaccharidesAlso: Endotoxin, LPS, Clinical reference center lipopolysaccharide, LPS E. Coli O:113LPS 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. | Drug | Asthma Group, Control Group |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lipopolysaccharides in people with Asthma; Eosinophilic and Asthma, run by National Jewish Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutrophil heterogeneity using single cell RNA sequencing (time frame: We anticipate that the study will run over 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2024; AzTrials last refreshed its copy on 7 Nov 2026.