Endotoxin Challenge for Lung Inflammation

Enrolling by invitation at 1 trial location

Overseen By Gloria Y Pastor, R.N.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institutes of Health Clinical Center (CC)

Must not be taking: Aspirin, NSAIDs

Disqualifiers: Smoking, Pregnancy, BMI >30, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the body's response to lung infections by studying a molecule called microRNA, which affects lung cells. Participants will receive a harmless molecule called endotoxin, which mimics an infection, to observe its influence on lung inflammation. The study divides participants into different groups to monitor reactions at various time points after introducing the endotoxin. Healthy, non-smoking adults with no significant medical issues are eligible to join. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Do I need to stop my current medications to join the trial?

Yes, you need to stop taking any medications, including aspirin or non-steroidal anti-inflammatory drugs, at least 7 days before participating in the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that endotoxin, a molecule from bacteria, can cause lung inflammation. Even one strong exposure to endotoxin can lead to noticeable lung inflammation. This reaction resembles what occurs during an infection, but endotoxin itself is not as harmful as an infection. High levels of exposure have been linked to breathing problems. Some studies suggest that endotoxin might worsen inflammation in individuals with existing lung issues.

However, the trial involves healthy adults who do not smoke, reducing the risk of serious side effects. The trial is in its middle stage, indicating that the treatment is considered somewhat safe, though risks are still under study. Researchers will closely monitor participants for changes in heart rate, temperature, and oxygen levels to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores how endotoxin can induce lung inflammation, which is crucial for understanding and eventually treating conditions like acute respiratory distress syndrome (ARDS). Unlike typical treatments that focus on managing symptoms after lung inflammation occurs, this approach challenges the body with endotoxin to study the process of inflammation itself. By using different time frames for lavage post-endotoxin exposure, researchers aim to identify the precise mechanisms and timelines of lung inflammation. This could lead to the development of more effective treatments that target inflammation early in its development.

What evidence suggests that this trial's treatments could be effective for lung inflammation?

Research has shown that endotoxin, a molecule from bacteria, can cause controlled inflammation in the lungs. In this trial, participants will receive endotoxin to study its effects on lung inflammation at different time points. Studies have found that exposure to endotoxin consistently leads to lung inflammation in healthy individuals. This helps researchers understand the body's reaction to infections and aids in studying lung conditions and potential treatments. Other research has demonstrated that some therapies can reduce this inflammation, offering ways to manage lung infections. Overall, using endotoxin in a controlled manner provides valuable insights into lung health and disease. ^{2 6 7 8 9}

Who Is on the Research Team?

Anthony F Suffredini, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Are You a Good Fit for This Trial?

Healthy adults aged 18-45 who don't smoke can join this trial. They shouldn't have any serious health issues or be on medications like aspirin. Ex-smokers must have quit for at least a year, and women need to use birth control or abstain from sex. Participants must also agree to sample storage.

Inclusion Criteria

I haven't taken aspirin or anti-inflammatory drugs in the last 7 days.

I quit smoking more than a year ago and smoked less than 10 pack-years. I haven't used hookah, e-cigarettes, or vaped regularly for at least 6 weeks.

I am using birth control or abstaining from sex.

Exclusion Criteria

I do not have any serious active health issues.

My BMI is over 30.

Pregnancy and/or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Endotoxin Challenge

Participants undergo bronchoscopy with bronchoalveolar lavage, and some receive endotoxin instillation to study lung inflammation

1 day

1 visit (in-person)

Observation and Follow-up

Participants are monitored for lung response to endotoxin at 6, 24, and 48 hours post-instillation

2 days

Multiple visits (in-person)

Post-procedure Follow-up

Participants are called the next day to assess their well-being

1 day

1 call (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Endotoxin
• Saline

Trial Overview The study is testing how the lungs respond to endotoxin, which mimics infection but isn't one, by comparing it with saline (salt water). Some participants will get endotoxin in their lungs and then undergo bronchoscopy after 6-48 hours to see the response.

How Is the Trial Designed?

Group I: 3 - Endotoxin Experimental Treatment 1 Intervention

48 hour lavage post endotoxin

Group II: 2 - Endotoxin Experimental Treatment 1 Intervention

24 hour lavage post endotoxin

Group III: 1 - Endotoxin Experimental Treatment 1 Intervention

6 hour lavage post endotoxin

Group IV: 4 Placebo comparator Placebo Group 1 Intervention

6 hour control lavage

Who Is Running the Clinical Trial?

National Institutes of Health Clinical Center (CC)

Lead Sponsor

Trials

391

Recruited

30,880,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5056796/

Reproducibility of the Inflammatory Response to Inhaled ... Data was obtained from 16 healthy control subjects who had undergone more than one inhalation challenge with a 20,000 endotoxin unit (EU) dose of Clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9569365/

Post-endotoxin exposure-induced lung inflammation and ... Short-term, lung-delivered rIL-10 favorably hastened inflammatory recovery processes following acute, high dose inhalant LPS exposure.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06677918

Study Details | NCT06677918 | Clinical Trial Investigating ... This is a randomized, double-blind, placebo-controlled trial in healthy adults. The study will assess the effect of repeated doses of EP395 on blood and lung ...

4. nature.com nature.com/articles/s41598-024-51547-0

Transcriptomic characterization of the human segmental ... The aim of this work was to describe the transcriptomic profile of human segmental LPS challenge with contextualization to major respiratory diseases.

5. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.70253

Lung‐delivered IL‐10 mitigates Lung inflammation induced by ... Lung-delivered IL-10 therapy administered after daily repeated endotoxin exposures strikingly reduces lung inflammatory and wound repair ...

6. stacks.cdc.gov stacks.cdc.gov/view/cdc/212684

Post-Endotoxin Exposure-Induced Lung Inflammation and ... Although lung diseases typically result from long-term exposures, even a robust, one-time exposure can result in long-lasting consequences.

7. ehjournal.biomedcentral.com ehjournal.biomedcentral.com/articles/10.1186/s12940-018-0360-7

Respiratory health effects of exposure to low levels of airborne ... There is clear evidence that occupational exposure to high concentrations of airborne endotoxin causes respiratory inflammation, respiratory ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0048969710000094

Modeling human health risks of airborne endotoxin in ... It is possible that the effect of concurrent exposure to endotoxin and PM could be especially deleterious in patients with preexisting lung inflammation due to ...

9. dovepress.com dovepress.com/synergistic-effects-of-resistive-breathing-on-endotoxin-induced-lung-i-peer-reviewed-fulltext-article-COPD

Endotoxin-induced acute lung injury | COPD The key outcome of our study is that resistive breathing exaggerates pulmonary inflammation and injury caused by either inhaled or ...