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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how lipopolysaccharides from bacteria affect the airways of people with asthma. Researchers aim to understand airway inflammation in different asthma types. The trial includes two groups: one with asthma and one without respiratory issues. Individuals diagnosed with asthma, especially those aware of their specific type (such as T2, T1, or T17), may be suitable candidates. Participants must not have experienced any recent illnesses or asthma attacks. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that lipopolysaccharides are likely to be safe for humans?

Research shows that certain substances called lipopolysaccharides (LPS) can affect asthma in different ways. Some studies indicate that exposure to LPS can worsen asthma symptoms by increasing airway inflammation, leading to more breathing problems for people with asthma.

Conversely, other research suggests that LPS exposure might protect against developing asthma or allergies when exposed to certain allergens. Thus, LPS can have both positive and negative effects, depending on the situation.

Since this study is in an early phase, it primarily aims to understand how LPS affects the body. This phase typically involves a small number of participants to assess treatment tolerance and check for any side effects. While evidence shows that LPS can cause inflammation, this study will clarify its role in asthma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Most treatments for asthma focus on managing symptoms through inhaled corticosteroids or bronchodilators, which reduce inflammation or relax airway muscles. However, lipopolysaccharides (LPS) offer a different approach by potentially modulating the immune system's response to environmental triggers. Researchers are excited about this because LPS could target the immune pathways more directly involved in asthma, potentially leading to more precise and effective management of the condition. This unique mechanism might pave the way for new strategies in treating different asthma endotypes, offering hope for patients who don't respond well to existing therapies.

What evidence suggests that lipopolysaccharides might be an effective treatment for asthma?

This trial will compare the effects of lipopolysaccharides (LPS) on individuals with asthma to those without asthma. Research has shown that LPS, derived from bacteria, can impact asthma in various ways. In animal studies, small amounts of LPS reduced certain gene activities in the lungs linked to asthma, suggesting it might help ease asthma symptoms. However, other studies found that LPS can also worsen airway inflammation by boosting certain immune responses. This indicates that LPS might affect people differently based on their specific type of asthma. While these findings are promising, they primarily come from animal studies, and more research is needed to understand how LPS will affect people with asthma. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5985709/

Lipopolysaccharide Exposure Alleviates Asthma in Mice by ... Analysis of these genes following OVA insult demonstrated that low-dose LPS pretreatment significantly reduced the expression of these genes in lung tissue ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26239413/

Lipopolysaccharide (LPS) Exposure Differently Affects ... Results: Exposure to LPS (0.1 μg) exacerbates airway inflammations in terms of IgE level, Th2-cytokine response (IL-4 and IL-5), histamine release, EPO and MPO ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0092867421001665

Review The basic immunology of asthma Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated ...

4. jacionline.org jacionline.org/article/S0091-6749(21)02668-3/fulltext

Recent advances in the immunopathogenesis of severe ... In this review, we explore the distinct endotypes and their mechanistic pathways that characterize the heterogeneity observed in severe asthma.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0925443924001650

Identifying ALOX15-initiated lipid peroxidation increases ... However, in 5–10 % of patients, the course of the disease remains difficult to control, probably due to different asthma endotypes leading to different ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1043466615300326

Lipopolysaccharide (LPS) exposure differently affects ... Lower dose of LPS exposure is better in exacerbating allergic asthma. •. Enhanced airway inflammations are dominated by eosinophils and neutrophils. •.

7. uab.edu uab.edu/news/research-innovation/how-lps-prevents-or-promotes-development-of-asthma-and-allergic-disease-by-airborne-allergens

How LPS prevents or promotes development of asthma ... Many experiments show that exposure to LPS during exposure to environmental allergens protects against developing asthma or allergic disease.

8. aacijournal.biomedcentral.com aacijournal.biomedcentral.com/articles/10.1186/s13223-019-0396-4

Co-exposure to lipopolysaccharide and desert dust causes ... Epidemiological studies have demonstrated that LPS exposure is a significant risk factor for increased asthma prevalence [1, 2]. LPS often ...