Acute Lung InflammationPhase 2NCT02392442
Effects of Bronchial Segmental Endotoxin Instillation in Humans
A Phase 2 study testing Saline and Endotoxin in people with Acute Lung Inflammation, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Background: When bacteria enter the lungs, serious infections can occur. Researchers want to learn more about the process of inflammation in the lungs by studying lung cells and the products that they make. Lung cells are influenced by infections, smoking, and molecules made within the body. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Lung Inflammation
- What is being tested?
- Saline and Endotoxin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2015to 30 Jun 2027
- Phase
- Phase 2
- 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 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy 18 to 45 year old, nonsmoking subjects based on screening examination and laboratory tests.
- No significant active medical problems. This would include but not be limited to any cardiac disorder (e.g. arrhythmia, valvular heart disease), pulmonary disease (e.g. asthma requiring chronic medications, chronic bronchitis, emphysema), neurologic disorder (e.g.
- epilepsy), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder (e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid disease), liver disease (e.g. hepatitis), gastrointestinal disorder (e.g. inflammatory bowel disease) or infectious
- disease (e.g. human immunodeficiency virus).
- No concurrent medications including aspirin or non-steroidal anti-inflammatory drugs or have not taken these for at least 7 days prior to study participation.
- Previous smokers would have to have abstained from cigarettes for at least one year and have no greater than a 10-pack year smoking history. If you use a hookah, e-cigarette, or vaping more than once a week, you must abstain for at least 6 weeks prior to participating in the study.
- Females must be practicing active method of birth control or abstinence of sexual activity.
- Must be willing to have samples stored
Who cannot join
- Any serious active medical problem as defined above
- Pregnancy and/or lactation
- BMI >30
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 Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Pulmonary Effects of Bronchial Segmental Endotoxin Instillation in Humans
Background:
- When bacteria enter the lungs, serious infections can occur. Researchers want to learn more about the process of inflammation in the lungs by studying lung cells and the products that they make. Lung cells are influenced by infections, smoking, and molecules made within the body. Researchers also want to learn more about one of these molecules, called microRNA (or micro ribonucleic acid).
Read more
Objective:
- To better how the body responds to infection. Also, to understand which cells in the lung secrete microRNA and how they may influence other lung cells.
Eligibility:
- Healthy, non-smoking adults ages 18-45.
Design:
- Participants will be screened with a medical history and physical exam. They will have blood and urine tests and an electrocardiogram.
- Participants will have blood drawn from an arm vein. They will have an intravenous catheter (small plastic tube) placed in a vein.
- All participants will have bronchoscopy with bronchoalveolar lavage. They will be numbed with medicine. A thin flexible tube will be placed through the nasal passages or the mouth into the airways of the lung.
- Some participants will have bronchoscopy with bronchoalveolar lavage (rinsing the airways with salt water) in order to obtain cells from lung. The water will then be suctioned out.
- Some participants will have two bronchoscopies; during the first procedure, endotoxin, a molecule found in bacteria is squirted into a small portion of the lung. Endotoxin is a molecule that acts like an infection but isn t one. After 6 to 48 hours, bronchoscopy with with bronchoalveolar lavage will be done to look at the lung s response to endotoxin.
- Participants heart rhythm and rate, temperature and blood oxygen level will be monitored during the procedures.
- Participants will be called the next day to see how they are feeling.
Read the detailed description
Defining the mechanisms that limit tissue injury during acute inflammation may provide the basis for preventing secondary organ dysfunction during serious infections. We plan to use the human endotoxin lung challenge model to study mechanisms associated with the initiation and resolution of lung inflammation.
Endotoxin (LPS), an outer membrane component of Gram-negative bacteria, is a major microbial factor that mediates inflammation associated with serious infections. For over fifty years, endotoxin has been administered to humans as a challenge agent in order to understand basic mechanisms of inflammation, to provide a proof of principle for pharmacologic interventions (e.g., anti-cytokines, corticosteroids), or as an adjuvant for immunotherapy of malignancies.
We previously developed a human model to study the initiation and resolution of inflammation in a lung segment following endotoxin bronchial instillation. The inflammatory response was limited to the challenged segment and had minimal associated systemic responses. After direct instillation into a lung segment, endotoxin elicits an inflammatory response characterized by the local production of inflammatory mediators, proteins and increases in cellularity. The predominate cell species found in the bronchoalveolar lavage (BAL) of the challenged segment changes from a neutrophil influx at 2 - 6 hours to an influx of monocytes and lymphocytes at 24 and 48 hours following endotoxin challenge. At 6 hours, BAL pro-inflammatory activity (i.e., tumor necrosis factor bioactivity and induction of intercellular adhesion molecule-1 on reporter cells) is present and absent at 24 and 48 hours post endotoxin. In addition, unique subsets of lymphocytes are present in the lung during this inflammatory response.
We have recently shown that non-cellular microRNAs (miRNAs) are present in archived BAL from normal healthy volunteer airways and are differentially expressed 6 hours after endotoxin-induced acute lung inflammation. miRNA are single stranded non-coding RNA that mediate posttranscriptional regulation of gene expression. Some extracellular miRNA species may modulate local and distant cell processes. miRNA can activate Toll-like receptors (TLRs) and have been described as blood biomarkers of different disease states. However, the specific role of extracellular or secreted miRNAs in the lung is poorly defined. Our research plan is designed to study the roles of miRNA in acute lung inflammation by investigating the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge. A panel of flow cytometry cell surface markers will be performed on blood and BAL cells and intracellular and secreted miRNA will be isolated from specific cell species (i.e., neutrophils, monocytes, macrophages, and lymphocytes). We hypothesize that miRNA will have a role in modulating the initiation and resolution of inflammation.
- Conditions
- Acute Lung Inflammation
- Being tested
- Saline, Endotoxin
- Keywords
- immunophenotypes, Bronchoalveolar Lavage, Bronchoscopy, Endotoxin Installation, niRNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineOther
Investigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6 hours after 1800 of normal Saline installed in six 30 mL aliquots into the left (lingual) and right (middle lobe) lung segments (360 mL total).
EndotoxinBiological
Investigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge.
| Study group | Role | What they receive |
|---|---|---|
| 1 - Endotoxin | Experimental | 6 hour lavage post endotoxin Receives: Biological: Endotoxin |
| 2 - Endotoxin | Experimental | 24 hour lavage post endotoxin Receives: Biological: Endotoxin |
| 3 - Endotoxin | Experimental | 48 hour lavage post endotoxin Receives: Biological: Endotoxin |
| 4 Placebo comparator | Placebo comparator | 6 hour control lavage Receives: Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of cell-associated and secreted miRNA with specific types of resident and inflammatory cells in the lung.
Identification of cell-associated and secreted miRNA.
Measured: 6, 24, or 48 hours after Endotoxin is instilled in the lung.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2015 (estimated)
- Study start18 Jun 2015
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Lung InflammationStudies 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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Anthony F Suffredini, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02392442
- Sponsor's protocol ID
- 150091
- Other IDs
- 15-CC-0091
- Status last verified
- 8 May 2026
- First submitted
- 18 Mar 2015
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Protocol is silent on IDP sharing.
Publications
O'Grady NP, Preas HL, Pugin J, Fiuza C, Tropea M, Reda D, Banks SM, Suffredini AF. Local inflammatory responses following bronchial endotoxin instillation in humans. Am J Respir Crit Care Med. 2001 Jun;163(7):1591-8. doi: 10.1164/ajrccm.163.7.2009111.
PubMed 11401879Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, Biller H, Krug N, Hohlfeld JM. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013 Mar 28;13:19. doi: 10.1186/1471-2466-13-19.
PubMed 23537365Sandstrom T, Bjermer L, Rylander R. Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid. Eur Respir J. 1992 Sep;5(8):992-6.
PubMed 1426208
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Effects of Bronchial Segmental Endotoxin Instillation in Humans
- ClinicalTrials.gov ID
- NCT02392442
- Acronym / sponsor ID
- 150091
- Conditions
- Acute Lung Inflammation
- Keywords
- immunophenotypes, Bronchoalveolar Lavage, Bronchoscopy, Endotoxin Installation, niRNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 18 Jun 2015 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 19 Mar 2015 (estimated)
- 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.
Background:
- When bacteria enter the lungs, serious infections can occur. Researchers want to learn more about the process of inflammation in the lungs by studying lung cells and the products that they make. Lung cells are influenced by infections, smoking, and molecules made within the body. Researchers also want to learn more about one of these molecules, called microRNA (or micro ribonucleic acid).
Objective:
- To better how the body responds to infection. Also, to understand which cells in the lung secrete microRNA and how they may influence other lung cells.
Eligibility:
- Healthy, non-smoking adults ages 18-45.
Design:
- Participants will be screened with a medical history and physical exam. They will have blood and urine tests and an electrocardiogram.
- Participants will have blood drawn from an arm vein. They will have an intravenous catheter (small plastic tube) placed in a vein.
- All participants will have bronchoscopy with bronchoalveolar lavage. They will be numbed with medicine. A thin flexible tube will be placed through the nasal passages or the mouth into the airways of the lung.
- Some participants will have bronchoscopy with bronchoalveolar lavage (rinsing the airways with salt water) in order to obtain cells from lung. The water will then be suctioned out.
- Some participants will have two bronchoscopies; during the first procedure, endotoxin, a molecule found in bacteria is squirted into a small portion of the lung. Endotoxin is a molecule that acts like an infection but isn t one. After 6 to 48 hours, bronchoscopy with with bronchoalveolar lavage will be done to look at the lung s response to endotoxin.
- Participants heart rhythm and rate, temperature and blood oxygen level will be monitored during the procedures.
- Participants will be called the next day to see how they are feeling.
Detailed description
Defining the mechanisms that limit tissue injury during acute inflammation may provide the basis for preventing secondary organ dysfunction during serious infections. We plan to use the human endotoxin lung challenge model to study mechanisms associated with the initiation and resolution of lung inflammation.
Endotoxin (LPS), an outer membrane component of Gram-negative bacteria, is a major microbial factor that mediates inflammation associated with serious infections. For over fifty years, endotoxin has been administered to humans as a challenge agent in order to understand basic mechanisms of inflammation, to provide a proof of principle for pharmacologic interventions (e.g., anti-cytokines, corticosteroids), or as an adjuvant for immunotherapy of malignancies.
We previously developed a human model to study the initiation and resolution of inflammation in a lung segment following endotoxin bronchial instillation. The inflammatory response was limited to the challenged segment and had minimal associated systemic responses. After direct instillation into a lung segment, endotoxin elicits an inflammatory response characterized by the local production of inflammatory mediators, proteins and increases in cellularity. The predominate cell species found in the bronchoalveolar lavage (BAL) of the challenged segment changes from a neutrophil influx at 2 - 6 hours to an influx of monocytes and lymphocytes at 24 and 48 hours following endotoxin challenge. At 6 hours, BAL pro-inflammatory activity (i.e., tumor necrosis factor bioactivity and induction of intercellular adhesion molecule-1 on reporter cells) is present and absent at 24 and 48 hours post endotoxin. In addition, unique subsets of lymphocytes are present in the lung during this inflammatory response.
We have recently shown that non-cellular microRNAs (miRNAs) are present in archived BAL from normal healthy volunteer airways and are differentially expressed 6 hours after endotoxin-induced acute lung inflammation. miRNA are single stranded non-coding RNA that mediate posttranscriptional regulation of gene expression. Some extracellular miRNA species may modulate local and distant cell processes. miRNA can activate Toll-like receptors (TLRs) and have been described as blood biomarkers of different disease states. However, the specific role of extracellular or secreted miRNAs in the lung is poorly defined. Our research plan is designed to study the roles of miRNA in acute lung inflammation by investigating the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge. A panel of flow cytometry cell surface markers will be performed on blood and BAL cells and intracellular and secreted miRNA will be isolated from specific cell species (i.e., neutrophils, monocytes, macrophages, and lymphocytes). We hypothesize that miRNA will have a role in modulating the initiation and resolution of inflammation.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 - Endotoxin | Experimental | Biological: Endotoxin6 hour lavage post endotoxin |
| 2 - Endotoxin | Experimental | Biological: Endotoxin24 hour lavage post endotoxin |
| 3 - Endotoxin | Experimental | Biological: Endotoxin48 hour lavage post endotoxin |
| 4 Placebo comparator | Placebo comparator | Other: Saline6 hour control lavage |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- epilepsy), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder (e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid disease), liver disease (e.g. hepatitis), gastrointestinal disorder (e.g. inflammatory bowel disease) or infectious
- disease (e.g. human immunodeficiency virus).
Key exclusion criteria (3 listed)
- Any serious active medical problem as defined above
- Pregnancy and/or lactation
- BMI >30
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 |
|---|---|---|
| SalineInvestigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6 hours after 1800 of normal Saline installed in six 30 mL aliquots into the left (lingual) and right (middle lobe) lung segments (360 mL total). | Other | 4 Placebo comparator |
| EndotoxinInvestigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge. | Biological | 1 - Endotoxin, 2 - Endotoxin, 3 - Endotoxin |
Primary outcome
Identification of cell-associated and secreted miRNA with specific types of resident and inflammatory cells in the lung.
Time frame: 6, 24, or 48 hours after Endotoxin is instilled in the lung.
Identification of cell-associated and secreted miRNA.
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 5 Nov 2026.
- Background: PubMed 11401879O'Grady NP, Preas HL, Pugin J, Fiuza C, Tropea M, Reda D, Banks SM, Suffredini AF. Local inflammatory responses following bronchial endotoxin instillation in humans. Am J Respir Crit Care Med. 2001 Jun;163(7):1591-8. doi: 10.1164/ajrccm.163.7.2009111.
- Background: PubMed 23537365Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, Biller H, Krug N, Hohlfeld JM. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013 Mar 28;13:19. doi: 10.1186/1471-2466-13-19.
- Background: PubMed 1426208Sandstrom T, Bjermer L, Rylander R. Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid. Eur Respir J. 1992 Sep;5(8):992-6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Protocol is silent on IDP sharing.
Related trials for Acute Lung Inflammation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
RecruitingPhase 2
Rademikibart IV for Acute Asthma and COPD Exacerbation
Asthma Acute, COPD Exacerbation Acute
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
RecruitingObservational study
CytOSorb TreatMent Of Critically Ill PatientS Registry
Septic Shock, Acute Respiratory Distress Syndrome
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.
Anthony F Suffredini, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saline and Endotoxin in people with Acute Lung Inflammation, run by National Institutes of Health Clinical Center (CC) 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 8 inclusion and 3 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: enrolling by invitation, as of the sponsor's last update on 5 Nov 2026. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of cell-associated and secreted miRNA with specific types of resident and inflammatory cells in the lung. (time frame: 6, 24, or 48 hours after Endotoxin is instilled in the lung.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02392442, which also lists 3 linked publications.
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 5 Nov 2026.