Endotoxin Challenge for Asthma

(Nasal-LPS Trial)

Overseen By Olivia M VerBurg, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Jewish Health

Must not be taking: Anticoagulants, Antiplatelets, Immunosuppressants

Disqualifiers: Cardiac disease, Immunocompromised, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it excludes those using systemic anticoagulants or antiplatelet therapy, so you may need to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Lipopolysaccharides for asthma?

There is no direct evidence from the provided research articles that supports the effectiveness of lipopolysaccharides as a treatment for asthma. The studies mainly discuss the role of endotoxins in asthma exacerbation and airway response, rather than their therapeutic benefits. ^{1 2 3 4 5}

Is inhaled lipopolysaccharide (endotoxin) generally safe for humans?

There is no published data on the short-term safety of inhaled endotoxin protocols in humans, although it has been used in studies for over 20 years to assess airway responses. ^{1 4 6 7 8}

How does the treatment Lipopolysaccharides differ from other asthma treatments?

Lipopolysaccharides (LPS) are used in a unique way for asthma by being inhaled to challenge the airways, which helps researchers understand how asthma is affected by environmental endotoxins. Unlike standard asthma treatments that aim to relieve symptoms or reduce inflammation, this approach is used to study the body's response to endotoxins and is not a typical treatment for managing asthma symptoms. ^{2 3 4 5 8}

Eligibility Criteria

This trial is for adults with asthma diagnosed by a healthcare provider and healthy individuals without asthma. It's not open to those who've used tobacco or marijuana recently, have had nasal surgery, current illness, recent severe asthma issues, nasal polyps, heart/systemic diseases, are pregnant/breastfeeding, have bleeding disorders or compromised immune systems.

Inclusion Criteria

Healthy controls are individuals without asthma

Written informed consent

I have been diagnosed with asthma by a doctor.

Exclusion Criteria

I have been ill in the last 4 weeks.

I have had an asthma attack in the last 4 weeks.

Currently pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Endotoxin Challenge

Participants receive intranasal administration of endotoxin to study neutrophil migration

1 day

1 visit (in-person)

Neutrophil Assessment

Neutrophils are isolated and assessed using nasal lavage and brushes at 20 minutes, 1 day, and 3 days post-challenge

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after endotoxin challenge

4 weeks

Treatment Details

Interventions

• Lipopolysaccharides

Trial Overview The study is testing how the body reacts to an intranasal lipopolysaccharide (a component from E. coli) challenge in people with different types of asthma compared to healthy controls. This phase I trial aims to understand airway inflammation mechanisms in various asthma endotypes.

Participant Groups

Group I: Asthma Group Active Control 1 Intervention

Subjects diagnosed with one of the three asthma endotypes being studied (T2, T1, or T17).

Group II: Control Group Active Control 1 Intervention

Subjects with no diagnosis of asthma or other respiratory disease and are deemed healthy.

Who Is Running the Clinical Trial?

National Jewish Health

Lead Sponsor

Trials

145

Recruited

318,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

LPS binding protein is important in the airway response to inhaled endotoxin. [2007]

2. United States pubmed.ncbi.nlm.nih.gov

Increased sputum endotoxin levels are associated with an impaired lung function response to oral steroids in asthmatic patients. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Enhancement of eosinophil survival by lipopolysaccharide through releasing granulocyte-macrophage colony stimulating factor from mononuclear cells from patients with bronchial asthma. [2004]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of incremental inhaled lipopolysaccharide challenge in humans. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

Nasal provocation test (NPT) with isolated and associated dermatophagoides pteronyssinus (Dp) and endotoxin lipopolysaccharide (LPS) in children with allergic rhinitis (AR) and nonallergic controls. [2013]

6. Ireland pubmed.ncbi.nlm.nih.gov

The effect of endotoxin on the production of IgE, IgG1 and IgG2a antibodies against the cat allergen Fel d 1 in mice. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Development of an inhaled endotoxin challenge protocol for characterizing evoked cell surface phenotype and genomic responses of airway cells in allergic individuals. [2021]