Ignite Creation Date:
2024-05-06 @ 3:53 AM
Last Modification Date:
2024-10-26 @ 11:40 AM
Study NCT ID:
NCT02392442
Status:
SUSPENDED
Last Update Posted:
2024-07-15
First Post:
2015-03-18
Brief Title:
Effects of Bronchial Segmental Endotoxin Instillation in Humans
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pulmonary Effects of Bronchial Segmental Endotoxin Instillation in Humans
Status:
SUSPENDED
Status Verified Date:
2024-07-15
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The expiration date of the endotoxin used under IND The sponsor has requested that there be a clinical hold placed on the study until the product has been show
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
- 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 eg 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 ie 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 ie neutrophils monocytes macrophages and lymphocytes We hypothesize that miRNA will have a role in modulating the initiation and resolution of 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 eg 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 ie 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 ie neutrophils monocytes macrophages and lymphocytes We hypothesize that miRNA will have a role in modulating the initiation and resolution of inflammation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 15-CC-0091 | None | None | None |