Intrabronchial Lipopolysaccharide for Acute Respiratory Distress Syndrome

Overseen By Kara Mould

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Jewish Health

Must not be taking: Anticoagulants, Antiplatelets, Immunosuppressants, others

Disqualifiers: Cardiac, Pulmonary, Systemic disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with Acute Respiratory Distress Syndrome (ARDS), a condition where fluid accumulates in the lungs, hindering breathing. Researchers use bronchoscopy, a procedure involving the insertion of a thin tube into the airways, to study how different immune cells in the lungs contribute to healing. The goal is to understand how to stop lung inflammation and promote healing. Individuals who are generally healthy, non-smokers, and have not used inhaled substances in the past three months may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatments for ARDS.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use systemic anticoagulants, antiplatelet therapy, or systemic immunosuppressants.

What prior data suggests that bronchoscopy is safe for this trial?

Research has shown that intrabronchial lipopolysaccharide (LPS) is often used in early studies to create lung injury similar to acute respiratory distress syndrome (ARDS). These studies help scientists understand how ARDS starts and develops. However, most of this research involves animals, not humans.

In these studies, LPS causes inflammation similar to that in human lung conditions. Because these results come from animal studies, the safety of LPS for humans remains unclear.

As this is an early phase trial, the main goal is to assess the treatment's safety and tolerability. Limited information exists about LPS's safety in humans. Participation in this trial would help researchers gather crucial safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this treatment for Acute Respiratory Distress Syndrome (ARDS) because it uses lipopolysaccharide (LPS) administered directly into the lungs via bronchoscopy. Unlike the standard of care, which often includes mechanical ventilation and supportive therapies, this approach targets the lungs more directly and could potentially modify the body's immune response more effectively. By using LPS, a component known to stimulate the immune system, this treatment may help reduce inflammation in a more controlled manner. This novel delivery method and mechanism of action are what make it stand out from existing therapies.

What evidence suggests that bronchoscopy might be an effective treatment for acute respiratory distress syndrome?

Research has shown that intrabronchial lipopolysaccharide (LPS) can cause lung inflammation similar to acute respiratory distress syndrome (ARDS) in animals. In these studies, LPS exposure resulted in serious lung damage, fluid buildup in the lungs, and low oxygen levels. This research aids scientists in understanding ARDS and testing new treatments. In this trial, participants in the LPS arm will receive LPS directly into the lungs using a bronchoscope (a thin tube with a camera), a method proven effective in animal studies. While these results are promising in animals, more research is needed to determine its effects on humans. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-50 who haven't used alcohol excessively or any inhaled substances recently. Pregnant or breastfeeding individuals, those with bleeding disorders, immunocompromised conditions, recent illnesses, heart/lung/systemic diseases, abnormal lung function tests or ECGs can't participate.

Inclusion Criteria

Written, informed consent

Exclusion Criteria

I have a bleeding disorder or I'm on blood thinners.

I have a weakened immune system due to a condition like HIV or medication.

You have been drinking a lot of alcohol in the past 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are exposed to endotoxin and macrophage activity is assessed

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bronchoscopy

Trial Overview The study involves a bronchoscopy procedure where lipopolysaccharide (a substance that can cause inflammation) is directly placed into the lungs to understand how different types of macrophages contribute to lung repair after injury.

How Is the Trial Designed?

Group I: LPS arm Experimental Treatment 1 Intervention

Bronchoscopy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

Approved in European Union as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

Approved in Canada as Bronchoscopy for:

• Diagnostic purposes
• Therapeutic interventions
• Airway management

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/PMC11963770/

Associated effects of lipopolysaccharide, oleic acid, and lung ... The model demonstrates severe lung damage, pulmonary edema, and sustained hypoxemia, providing a basis for future research. Keywords: acute ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12306704/

Comparative Evaluation of Lipopolysaccharide Administration ... Direct preclinical lipopolysaccharide acute lung injury (ALI) models are commonly used to study acute respiratory distress syndrome.

3. nature.com nature.com/articles/s41598-021-87462-x

Intranasal versus intratracheal exposure to ... We conclude that an intranasal exposure is as effective as an intratracheal exposure in a murine model of ARDS induced by LPS. Additionally, the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1467298720302269

Targeted fibre-optical intrabronchial lipopolysaccharide ... The present study shows that targeted, intrabronchial drug administration via fibre-optic bronchoscopy is feasible and effective in a porcine model.

5. publications.ersnet.org publications.ersnet.org/content/erj/42/1/188

Intrabronchial activated protein C enhances ... Abstract. Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9121120/

Prevention of endotoxemia-induced acute respiratory ... An anti-IL-8 antibody treatment almost completely prevented pulmonary edema, destruction of pulmonary architecture, and impairment in gas exchange.

7. nature.com nature.com/articles/s41392-025-02127-9

Advances in acute respiratory distress syndrome This data has been used to argue the design of a clinical trial aimed at investigating acetaminophen's effectiveness as a treatment for ARDS.