Respiratory Distress Syndrome, AdultPhase 1NCT00094406
Carbon Monoxide to Prevent Lung Inflammation
A Phase 1 study testing Bronchoscopy, Bronchoalveolar lavage and Endotoxin in people with Respiratory Distress Syndrome, Adult, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
This study will examine in healthy volunteers how breathing carbon monoxide (CO) affects lung inflammation. Severe lung inflammation sometimes develops in patients with pneumonia or patients who develop serious blood stream infections. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Respiratory Distress Syndrome, Adult
- What is being tested?
- Bronchoscopy, Bronchoalveolar lavage and Endotoxin
- Type of treatment
- Surgery or procedure
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2004to 11 Mar 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All volunteer subjects, employees and non-employees, must 18 to 40 years of age and must be able to provide informed, written consent for participation in this study. We will not directly advertise the study to employees to avoid the potential for coercion. Eligibility in the study is determined prior to enrollment on the basis of the following inclusion and exclusion criteria.
- Normal screening examination including:
- medical history and physical examination, nonsmoker, no concurrent medications including aspirin or nonsteroidal anti-inflammatory drugs, no active medical problems
- complete blood count with differential and platelet counts
- serum chemistries including creatinine, blood urea nitrogen, glucose, liver enzymes and function tests, electrolytes, prothrombin time, partial thromboplastin time, carboxyhemoglobin measured by venous co-oxymetry.
- urinalysis
Show all 10Show fewer
- female subjects must have negative urine pregnancy test within one week of participation (this will be repeated immediately prior to beginning the screening procedures due to radiation exposure from the chest x-ray)
- electrocardiogram
- chest radiograph
- Sexually active females not using contraceptive methods will be instructed to abstain from sexual activity or use barrier contraception methods from the time of last negative pregnancy test to 24 hours after completion of the study.
Who cannot join
- active tobacco use
- baseline caroxyhemoglobin greater than 2%
- pregnancy
- lactation
- medical history of recent clinically significant asthma allergy to both sulfa- and penicillin-based drugs
- Allergy to both sulfa- and penicillin-based drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effects of Inhaled Carbon Monoxide on Pulmonary Inflammatory Responses Following Endotoxin Instillation
This study will examine in healthy volunteers how breathing carbon monoxide (CO) affects lung inflammation. Severe lung inflammation sometimes develops in patients with pneumonia or patients who develop serious blood stream infections. Studies in the laboratory and in animals show that CO can decrease lung inflammation.
Healthy volunteers between 18 and 40 years of age who do not smoke, are not taking any medications, do not have asthma, are not allergic to sulfa- and penicillin-based drugs, and are not pregnant may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), and chest x-ray. Subjects are enrolled in either a pilot study or the main study.
Read more
Participants undergo bronchoscopy and bronchoalveolar lavage to study the effects of endotoxin (a component of bacteria that causes inflammation similar to that in patients with lung infections) on lung function. Before the procedure, a small plastic tube (catheter) is placed in a vein to collect blood samples and another is placed in an artery to check blood pressure. For the bronchoscopy, the mouth and nasal airways are numbed with lidocaine, and a bronchoscope (thin flexible tube) is passed through the nose into the airways of the lung. A small amount of salt water is squirted through the bronchoscope into one lung and then salt water containing endotoxin is squirted into the other lung.
Following the bronchoscopy, subjects are treated with either CO or room air (placebo) for 6 hours. (Subjects in the pilot study receive treatment for only 3 hours). The gas is delivered through a cushioned mask placed over the nose and mouth. The amount of exhaled CO is measured before, during, and after inhalation of the gas. For this measurement, subjects take a deep breath to fill up their lungs and slowly exhale into a mouthpiece connected to a measuring device until they feel their lungs are empty.
After the CO treatment, a second bronchoscopy is done to examine how the lung responded to the CO or room air. This is studied in two ways. To sample the air, a large needle is used to withdraw air through the bronchoscope over about 3 seconds. Then the areas of the lung that were squirted with salt water alone and with endotoxin and salt water and are rinsed (lavage) and cells and secretions are collected.
...
Read the detailed description
Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality. Of the many potential predisposing factors, sepsis and pneumonia represent the two main causes of ARDS. In spite of an increase in survival in recent years mortality in patients with ARDS is still estimated around 30 to 40%. In this context, development of effective preventive strategies in patients at high risk of development of ARDS is of paramount importance. Unfortunately, the results of studies evaluating prophylactic regimens for ARDS have been mostly disappointing.
The gaseous molecule carbon monoxide (CO) has been traditionally viewed as a toxic metabolic and industrial waste. However, recent studies have demonstrated an important physiologic role of CO in many biological systems. Specifically, strong anti-inflammatory, anti-oxidant and anti-thrombotic effects of CO gas administration and heme oxygenase activation (the enzyme that generates endogenous CO gas) have been demonstrated in several animal models.
Previous studies conducted in our department have demonstrated that bronchoscopic instillation of endotoxin (LPS) in healthy volunteers elicits a compartmentalized pulmonary inflammatory response, serving as an excellent model to evaluate interventions directed towards suppression of lung inflammation at its earliest stages.
In the current single blinded, randomized, placebo controlled study, we are planning to evaluate the effects of inhaled carbon monoxide on local pulmonary inflammatory responses following endotoxin administration. Healthy subjects will undergo local endotoxin instillation, breathe CO or room air through a mask for 6 hours, and then a repeat bronchoscopy with lavage will be done at 6 hours to assess the ability of CO to suppress local inflammation in the lung.
- Conditions
- Respiratory Distress Syndrome, Adult
- Being tested
- Bronchoscopy, Bronchoalveolar lavage, Endotoxin, Carbon Monoxide
- Keywords
- Lung Permeability, Endotoxin Tolerance, Bronchoscopy, Carbon Monoxide Inhalation
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BronchoscopyProcedure or surgery
Bronchoalveolar lavageProcedure or surgery
EndotoxinDrug
Carbon MonoxideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2004 (estimated)
- Study start13 Oct 2004
- Primary completion11 Mar 2010
- Study completion11 Mar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, AdultStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 35 participants (actual)
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
- NCT00094406
- Sponsor's protocol ID
- 050012
- Other IDs
- 05-CC-0012
- Status last verified
- 19 Apr 2016
- First submitted
- 16 Oct 2004
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301. doi: 10.1164/ajrccm.151.2.7842182.
PubMed 7842182Baumann WR, Jung RC, Koss M, Boylen CT, Navarro L, Sharma OP. Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital. Crit Care Med. 1986 Jan;14(1):1-4. doi: 10.1097/00003246-198601000-00001.
PubMed 3484443Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA. 1995 Jan 25;273(4):306-9.
PubMed 7815658Zhang T, Zhang G, Chen X, Chen Z, Tan AY, Lin A, Zhang C, Torres LK, Bajrami S, Zhang T, Zhang G, Xiang JZ, Hissong EM, Chen YT, Li Y, Du YN. Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells. Cancer Lett. 2022 Oct 10;546:215831. doi: 10.1016/j.canlet.2022.215831. Epub 2022 Jul 19.
PubMed 35868533
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Inhaled Carbon Monoxide on Pulmonary Inflammatory Responses Following Endotoxin Instillation
- ClinicalTrials.gov ID
- NCT00094406
- Acronym / sponsor ID
- 050012
- Conditions
- Respiratory Distress Syndrome, Adult
- Keywords
- Lung Permeability, Endotoxin Tolerance, Bronchoscopy, Carbon Monoxide Inhalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 13 Oct 2004
- Primary completion
- 11 Mar 2010 (actual)
- Study completion
- 11 Mar 2010 (actual)
- First posted
- 18 Oct 2004 (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.
This study will examine in healthy volunteers how breathing carbon monoxide (CO) affects lung inflammation. Severe lung inflammation sometimes develops in patients with pneumonia or patients who develop serious blood stream infections. Studies in the laboratory and in animals show that CO can decrease lung inflammation.
Healthy volunteers between 18 and 40 years of age who do not smoke, are not taking any medications, do not have asthma, are not allergic to sulfa- and penicillin-based drugs, and are not pregnant may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), and chest x-ray. Subjects are enrolled in either a pilot study or the main study.
Participants undergo bronchoscopy and bronchoalveolar lavage to study the effects of endotoxin (a component of bacteria that causes inflammation similar to that in patients with lung infections) on lung function. Before the procedure, a small plastic tube (catheter) is placed in a vein to collect blood samples and another is placed in an artery to check blood pressure. For the bronchoscopy, the mouth and nasal airways are numbed with lidocaine, and a bronchoscope (thin flexible tube) is passed through the nose into the airways of the lung. A small amount of salt water is squirted through the bronchoscope into one lung and then salt water containing endotoxin is squirted into the other lung.
Following the bronchoscopy, subjects are treated with either CO or room air (placebo) for 6 hours. (Subjects in the pilot study receive treatment for only 3 hours). The gas is delivered through a cushioned mask placed over the nose and mouth. The amount of exhaled CO is measured before, during, and after inhalation of the gas. For this measurement, subjects take a deep breath to fill up their lungs and slowly exhale into a mouthpiece connected to a measuring device until they feel their lungs are empty.
After the CO treatment, a second bronchoscopy is done to examine how the lung responded to the CO or room air. This is studied in two ways. To sample the air, a large needle is used to withdraw air through the bronchoscope over about 3 seconds. Then the areas of the lung that were squirted with salt water alone and with endotoxin and salt water and are rinsed (lavage) and cells and secretions are collected.
...
Detailed description
Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality. Of the many potential predisposing factors, sepsis and pneumonia represent the two main causes of ARDS. In spite of an increase in survival in recent years mortality in patients with ARDS is still estimated around 30 to 40%. In this context, development of effective preventive strategies in patients at high risk of development of ARDS is of paramount importance. Unfortunately, the results of studies evaluating prophylactic regimens for ARDS have been mostly disappointing.
The gaseous molecule carbon monoxide (CO) has been traditionally viewed as a toxic metabolic and industrial waste. However, recent studies have demonstrated an important physiologic role of CO in many biological systems. Specifically, strong anti-inflammatory, anti-oxidant and anti-thrombotic effects of CO gas administration and heme oxygenase activation (the enzyme that generates endogenous CO gas) have been demonstrated in several animal models.
Previous studies conducted in our department have demonstrated that bronchoscopic instillation of endotoxin (LPS) in healthy volunteers elicits a compartmentalized pulmonary inflammatory response, serving as an excellent model to evaluate interventions directed towards suppression of lung inflammation at its earliest stages.
In the current single blinded, randomized, placebo controlled study, we are planning to evaluate the effects of inhaled carbon monoxide on local pulmonary inflammatory responses following endotoxin administration. Healthy subjects will undergo local endotoxin instillation, breathe CO or room air through a mask for 6 hours, and then a repeat bronchoscopy with lavage will be done at 6 hours to assess the ability of CO to suppress local inflammation in the lung.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- All volunteer subjects, employees and non-employees, must 18 to 40 years of age and must be able to provide informed, written consent for participation in this study. We will not directly advertise the study to employees to avoid the potential for coercion. Eligibility in the study is determined prior to enrollment on the basis of the following inclusion and exclusion criteria.
- medical history and physical examination, nonsmoker, no concurrent medications including aspirin or nonsteroidal anti-inflammatory drugs, no active medical problems
- complete blood count with differential and platelet counts
- serum chemistries including creatinine, blood urea nitrogen, glucose, liver enzymes and function tests, electrolytes, prothrombin time, partial thromboplastin time, carboxyhemoglobin measured by venous co-oxymetry.
- urinalysis
Key exclusion criteria (6 listed)
- active tobacco use
- baseline caroxyhemoglobin greater than 2%
- pregnancy
- lactation
- medical history of recent clinically significant asthma allergy to both sulfa- and penicillin-based drugs
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 |
|---|---|---|
| Bronchoscopy | Procedure or surgery | – |
| Bronchoalveolar lavage | Procedure or surgery | – |
| Endotoxin | Drug | – |
| Carbon Monoxide | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 7842182Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301. doi: 10.1164/ajrccm.151.2.7842182.
- Background: PubMed 3484443Baumann WR, Jung RC, Koss M, Boylen CT, Navarro L, Sharma OP. Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital. Crit Care Med. 1986 Jan;14(1):1-4. doi: 10.1097/00003246-198601000-00001.
- Background: PubMed 7815658Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA. 1995 Jan 25;273(4):306-9.
- Derived from this study: PubMed 35868533Zhang T, Zhang G, Chen X, Chen Z, Tan AY, Lin A, Zhang C, Torres LK, Bajrami S, Zhang T, Zhang G, Xiang JZ, Hissong EM, Chen YT, Li Y, Du YN. Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells. Cancer Lett. 2022 Oct 10;546:215831. doi: 10.1016/j.canlet.2022.215831. Epub 2022 Jul 19.
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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. This study is not recruiting at the moment.
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 1 study testing Bronchoscopy, Bronchoalveolar lavage and Endotoxin in people with Respiratory Distress Syndrome, Adult, 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 10 inclusion and 6 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: finished, as of the sponsor's last update on 17 Dec 2019. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094406, which also lists 4 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 17 Dec 2019.