Ignite Creation Date:
2024-05-05 @ 10:18 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001303
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
1999-11-03
Brief Title:
Effects of Endotoxin in Normal Human Volunteers
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Cardiopulmonary Effects of Endotoxin in Normal Human Volunteers
Status:
COMPLETED
Status Verified Date:
2018-05-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bacterial infections can progress to a life-threatening illness called septic shock characterized by low blood pressure and vital organ damage The syndrome is thought to be caused by parts of the bacteria and by the body s own immune response to the infection A major bacterial product that interacts with the immune defenses is called endotoxin This study will examine the body s response to endotoxin in the lungs or bloodstream When endotoxin is given in small amounts to humans even though it is not an infection it triggers a set of responses that are typical of what one would see with a true bacterial infection This allows us to study the earliest changes in molecules and cells that are involved in some bacterial infections This type of model is safe and has been used in humans for many years to understand the body s responses during infections
Normal volunteers 18 to 45 years of age may be eligible for this study Candidates will have a history and physical examination blood and urine tests electrocardiogram EKG and chest X-ray In addition volunteers 40 to 45 years old will have an exercise stress test to screen for asymptomatic coronary artery disease Participants will undergo one or more of the following procedures
Bronchoscopy Bronchoalveolar Lavage Bronchial Brushings and Endobronchial Mucosal Biopsies These techniques for examining lung function are used routinely in patient care and clinical research The mouth and nasal and lung airways are numbed with an anesthetic A bronchoscope pencil-thin flexible tube is then passed through the nose into the large airways of the lung Cells and secretions from the airways are rinsed with salt water bronchoalveolar lavage and a flexible brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways Lastly pieces of tissue the size of the ball of a ballpoint pen lining the airways are removed for examination under the microscope
Intravenous Endotoxin A small dose of endotoxin is injected into a vein Blood samples are drawn at regular intervals for 8 hours after the injection and again after 1 2 3 7 and 14 days to analyze the body s immune response to the bacteria in the blood
Instilled Endotoxin in the Lungs A small amount 2 teaspoons of salt water is squirted through a bronchoscope into a lobe of one lung and then salt water containing a small dose of endotoxin is squirted into the other lung Bronchial lavage brushing and biopsy see above are then done to study the response of the lung to the endotoxin In addition air is withdrawn through the bronchoscope to study air components from the lung that was instilled with salt water or endotoxin
Nitric Oxide Therapy Endotoxin is instilled in a lung see above and then nitric oxide a colorless odorless tasteless gas mixed with room air in a concentration of 40 parts per million is given through a cushioned mask placed over the mouth and nose Some participants will be given the nitric oxide mixture and others will breathe only room air through the mask to test the effects of the nitric oxide on the lung inflammation The mask will be worn continuously for 6 hours and removed before repeat bronchoscopy with lavage brushing and biopsy
Some of the above procedures require placement of a catheter thin plastic tube in a wrist artery to monitor blood pressure from heartbeat to heartbeat and to collect blood samples First the skin is numbed with an anesthetic lidocaine A needle is then inserted into the artery the catheter is slipped over the needle into the vessel and the needle is removed
Normal volunteers 18 to 45 years of age may be eligible for this study Candidates will have a history and physical examination blood and urine tests electrocardiogram EKG and chest X-ray In addition volunteers 40 to 45 years old will have an exercise stress test to screen for asymptomatic coronary artery disease Participants will undergo one or more of the following procedures
Bronchoscopy Bronchoalveolar Lavage Bronchial Brushings and Endobronchial Mucosal Biopsies These techniques for examining lung function are used routinely in patient care and clinical research The mouth and nasal and lung airways are numbed with an anesthetic A bronchoscope pencil-thin flexible tube is then passed through the nose into the large airways of the lung Cells and secretions from the airways are rinsed with salt water bronchoalveolar lavage and a flexible brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways Lastly pieces of tissue the size of the ball of a ballpoint pen lining the airways are removed for examination under the microscope
Intravenous Endotoxin A small dose of endotoxin is injected into a vein Blood samples are drawn at regular intervals for 8 hours after the injection and again after 1 2 3 7 and 14 days to analyze the body s immune response to the bacteria in the blood
Instilled Endotoxin in the Lungs A small amount 2 teaspoons of salt water is squirted through a bronchoscope into a lobe of one lung and then salt water containing a small dose of endotoxin is squirted into the other lung Bronchial lavage brushing and biopsy see above are then done to study the response of the lung to the endotoxin In addition air is withdrawn through the bronchoscope to study air components from the lung that was instilled with salt water or endotoxin
Nitric Oxide Therapy Endotoxin is instilled in a lung see above and then nitric oxide a colorless odorless tasteless gas mixed with room air in a concentration of 40 parts per million is given through a cushioned mask placed over the mouth and nose Some participants will be given the nitric oxide mixture and others will breathe only room air through the mask to test the effects of the nitric oxide on the lung inflammation The mask will be worn continuously for 6 hours and removed before repeat bronchoscopy with lavage brushing and biopsy
Some of the above procedures require placement of a catheter thin plastic tube in a wrist artery to monitor blood pressure from heartbeat to heartbeat and to collect blood samples First the skin is numbed with an anesthetic lidocaine A needle is then inserted into the artery the catheter is slipped over the needle into the vessel and the needle is removed
Detailed Description:
Endotoxin is a unique molecule because it represents an important probe for investigating the humoral and cellular basis of septic shock Endotoxin administration to humans provides an opportunity to evaluate the earliest responses that are activated after exposure to an important bacterial component Many alterations in organ function and circulating mediators can be evaluated in this model These changes are qualitatively similar to changes that occur during sepsis and septic shock The applications of new technologies to this model are useful adjuncts to define mechanisms of acute inflammatory responses Defining these pathways and their interactions may allow a better understanding of the factors that can be controlled or altered during critical illness
In the current study we are planning to extend previous observations on heart and lung function after endotoxin administration in four separate studies
1 Bronchoalveolar lavage and bronchial brushings in normal subjects Bronchoalveolar lavage and bronchial brushings will be performed in normal subjects to obtain alveolar and epithelial pulmonary cells for use in vitro assays of respiratory cell function
2 Inflammatory effects of systemic endotoxin administration In order to evaluate late inflammatory responses to IV endotoxin blood will be obtained acutely and at 1 2 3 7 and 14 days post endotoxin challenge
3 Pulmonary effects of instilled endotoxin Using bronchoscopy the effects of direct instillation of endotoxin into a lobe of the lung is being used to assess local pulmonary inflammatory responses that result in neutrophil influx into the lung
4 Effects of inhaled nitric oxide on pulmonary inflammatory responses following endotoxin administration In order to systematically study the effects of inhaled nitric oxide on local lung inflammation healthy subjects will undergo local endotoxin instillation breath NO through a mask for 6h and then a repeat bronchoscopy will be done at 6h to assess the ability of NO to suppress local inflammation in the lung
In the current study we are planning to extend previous observations on heart and lung function after endotoxin administration in four separate studies
1 Bronchoalveolar lavage and bronchial brushings in normal subjects Bronchoalveolar lavage and bronchial brushings will be performed in normal subjects to obtain alveolar and epithelial pulmonary cells for use in vitro assays of respiratory cell function
2 Inflammatory effects of systemic endotoxin administration In order to evaluate late inflammatory responses to IV endotoxin blood will be obtained acutely and at 1 2 3 7 and 14 days post endotoxin challenge
3 Pulmonary effects of instilled endotoxin Using bronchoscopy the effects of direct instillation of endotoxin into a lobe of the lung is being used to assess local pulmonary inflammatory responses that result in neutrophil influx into the lung
4 Effects of inhaled nitric oxide on pulmonary inflammatory responses following endotoxin administration In order to systematically study the effects of inhaled nitric oxide on local lung inflammation healthy subjects will undergo local endotoxin instillation breath NO through a mask for 6h and then a repeat bronchoscopy will be done at 6h to assess the ability of NO to suppress local inflammation in the lung
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 92-CC-0141 | None | None | None |