Healthy ControlsPhase 1NCT00838851
Response of Airway Cells to 20,000 EU of Endotoxin in Normal Adults
A Phase 1 study testing Clinical Center Reference Endotoxin (CCRE) in people with Healthy Controls, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to determine the range of neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Controls
- What is being tested?
- Clinical Center Reference Endotoxin (CCRE)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2003to Jul 2012
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Inclusion: Healthy, non-allergic, non-asthmatic 18-50 year old males and females with a < 0.5 pack year history of tobacco use who have a negative allergy skin test, normal lung function, defined as (Knudsen 1976/1984 predicted set):
- FVC of > 80 % of that predicted for gender, ethnicity, age and height
- FEV1 of > 80 % of that predicted for gender, ethnicity, age and height
- FEV1/FVC ratio of > 75% of that predicted for gender, ethnicity , age and height
- Oxygen saturation of > 94 %,
- Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg),
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- Symptom Score no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score. No score may be greater than 2,
- Negative methacholine inhalation challenge.
- On the day of a challenge, body temperature must be no greater than 37.8 degrees, measured orally.
Who cannot join
- A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or asthma, hypertension).
- Allergy to any medications which may be used in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose).
- Positive pregnancy test within 48 hours of the time of challenge.
- Medications which may impact the results of the endotoxin challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
- Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 2 weeks.
- Unspecified illnesses, which in the judgment of the investigator increase the risk associated with endotoxin inhalation challenge, will be a basis for exclusion.
- Persons employed within the past 6 months in an occupation with high risk for endotoxin exposure (specifically persons working in a swine confinement facility, cotton storage or grain storage site)
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Center for Environmental Medicine, Asthma and Lung Biology
Chapel Hill, North Carolina, 27599-7310
About this study
Official title: Range of Neutrophil Response to 20,000 EU of Clinical Center Reference Endotoxin in Normal Adult
The purpose of this study is to determine the range of neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU).
Read the detailed description
Twenty-four or forty-eight hours (study day 1) prior to the inhalation challenge, subjects will undergo a physical examination of the ears, nose, throat and chest and will have an assessment of vital signs (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, symptom score assessment and undergo spirometry to rule out acute illness prior to challenge. All female volunteers will undergo a urine pregnancy test. A similar examination will take place immediately prior to inhalation challenge with 20,000 EU of CCRE, as well as 30, 60, 120, 180, 240, 300 and 360 minutes and 24 hours after challenge (with the exception of a pregnancy test which will only be administered prior to sputum induction on study day 1). Induced sputum will be 24 to 48 hours prior to challenge, and again six hours after challenge on Study day 2. Sputum will be analyzed for PMN content, CD14 expression on airway macrophages and monocytes, soluble CD14 levels, cytokine levels in sputum and products of inflammatory cells (eosinophil, cationic protein, myeloperoxidase). Blood will be collected for a CBC and differential when the pre- challenge induced sputum is obtained and again 6 hours after challenge and 24 hours after challenge. Blood lymphocytes from a 10 ml aliquot will be assessed for lymphocyte subset and activation markers, as well as proliferative and cytokine responses. Blood will also be collected and will be assessed by whole blood assays for markers of inflammatory and immune activation (CD11b, CD14, CD64, CD16, HLA-DR, CD45, CD3, CD80, CD86, CD83, CD40) and function (phagocytosis and oxidative burst) by three color flow cytometry. Plasma will be separated from 4 ml and frozen at 70° C for future analysis of mediators of interest, such as cytokines, as well as other systemic effects of endotoxin.
Subjects will then be discharged to home with contact information for study staff. If a volunteer has an unexpected complication such as shortness of breath, decrease in pulmonary function, unstable vital signs or other he or she will be admitted to the GCRC for overnight observation. The next morning (study day 3) subjects will return to the CEMALB for a final set of vital signs, spirometry, symptom scoring, a venipuncture and an examination by a study physician.
Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4 days) after challenge.
Each sheet will include the name and phone number of the study coordinator and study MD. Sample home symptom scoring sheets and instructions are included with this protocol.
Between 48 and 96 hours after challenge, each volunteer will be called to determine their status, inquiring about symptoms, symptom scoring, and need for medication and/or physician visits.
Between 7 and 10 days of the challenge dose, each subject will be asked to return for a study discontinuation visit. At that time temperature, pulse, systolic and diastolic BP, respiratory rate, FVC and FEV1 and SpO2 (oxygen saturation), and symptoms scores will be assessed and, if abnormal, medical evaluation as directed by the study physician will be undertaken.
- Conditions
- Healthy Controls
- Being tested
- Clinical Center Reference Endotoxin (CCRE)
- Keywords
- endotoxin, CCRE, LPS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical Center Reference Endotoxin (CCRE)Biological
Also called LPS
Inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE)
| Study group | Role | What they receive |
|---|---|---|
| CCRE | Experimental | Not described Receives: Biological: Clinical Center Reference Endotoxin (CCRE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU),
Measured: 0-24 hours post challenge
Secondary outcomes (1)
changes in PFT's and vital signs
Measured: 0-21 days post challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2009 (estimated)
- Study startAug 2003
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: no further funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ControlsStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- Responsible party
- Principal investigator, David B. Peden, MD, University of North Carolina, Chapel Hill
- Investigators
- David B Peden, MD, MS, Principal investigator, University of North Carolina at Chapel Hill, Dept of Pediatrics / Center for Environmental Medicine, Asthma and Lung Biology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00838851
- Sponsor's protocol ID
- 03-1523 (GCRC 2040)
- Other IDs
- 1RC1ES018417
- Status last verified
- Oct 2012
- First submitted
- 6 Feb 2009
- Last updated
- 8 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Range of Neutrophil Response to 20,000 EU of Clinical Center Reference Endotoxin in Normal Adult
- ClinicalTrials.gov ID
- NCT00838851
- Acronym / sponsor ID
- 03-1523 (GCRC 2040)
- Conditions
- Healthy Controls
- Keywords
- endotoxin, CCRE, LPS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: no further funding
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- Study start
- Aug 2003
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 9 Feb 2009 (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.
The purpose of this study is to determine the range of neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU).
Detailed description
Twenty-four or forty-eight hours (study day 1) prior to the inhalation challenge, subjects will undergo a physical examination of the ears, nose, throat and chest and will have an assessment of vital signs (temperature, pulse, respiratory rate, blood pressure), oxygen saturation, symptom score assessment and undergo spirometry to rule out acute illness prior to challenge. All female volunteers will undergo a urine pregnancy test. A similar examination will take place immediately prior to inhalation challenge with 20,000 EU of CCRE, as well as 30, 60, 120, 180, 240, 300 and 360 minutes and 24 hours after challenge (with the exception of a pregnancy test which will only be administered prior to sputum induction on study day 1). Induced sputum will be 24 to 48 hours prior to challenge, and again six hours after challenge on Study day 2. Sputum will be analyzed for PMN content, CD14 expression on airway macrophages and monocytes, soluble CD14 levels, cytokine levels in sputum and products of inflammatory cells (eosinophil, cationic protein, myeloperoxidase). Blood will be collected for a CBC and differential when the pre- challenge induced sputum is obtained and again 6 hours after challenge and 24 hours after challenge. Blood lymphocytes from a 10 ml aliquot will be assessed for lymphocyte subset and activation markers, as well as proliferative and cytokine responses. Blood will also be collected and will be assessed by whole blood assays for markers of inflammatory and immune activation (CD11b, CD14, CD64, CD16, HLA-DR, CD45, CD3, CD80, CD86, CD83, CD40) and function (phagocytosis and oxidative burst) by three color flow cytometry. Plasma will be separated from 4 ml and frozen at 70° C for future analysis of mediators of interest, such as cytokines, as well as other systemic effects of endotoxin.
Subjects will then be discharged to home with contact information for study staff. If a volunteer has an unexpected complication such as shortness of breath, decrease in pulmonary function, unstable vital signs or other he or she will be admitted to the GCRC for overnight observation. The next morning (study day 3) subjects will return to the CEMALB for a final set of vital signs, spirometry, symptom scoring, a venipuncture and an examination by a study physician.
Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4 days) after challenge.
Each sheet will include the name and phone number of the study coordinator and study MD. Sample home symptom scoring sheets and instructions are included with this protocol.
Between 48 and 96 hours after challenge, each volunteer will be called to determine their status, inquiring about symptoms, symptom scoring, and need for medication and/or physician visits.
Between 7 and 10 days of the challenge dose, each subject will be asked to return for a study discontinuation visit. At that time temperature, pulse, systolic and diastolic BP, respiratory rate, FVC and FEV1 and SpO2 (oxygen saturation), and symptoms scores will be assessed and, if abnormal, medical evaluation as directed by the study physician will be undertaken.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CCRE | Experimental | Biological: Clinical Center Reference Endotoxin (CCRE) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Inclusion: Healthy, non-allergic, non-asthmatic 18-50 year old males and females with a < 0.5 pack year history of tobacco use who have a negative allergy skin test, normal lung function, defined as (Knudsen 1976/1984 predicted set):
- Oxygen saturation of > 94 %,
- Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg),
- Symptom Score no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score. No score may be greater than 2,
- Negative methacholine inhalation challenge.
Key exclusion criteria (7 listed)
- A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or asthma, hypertension).
- Allergy to any medications which may be used in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose).
- Positive pregnancy test within 48 hours of the time of challenge.
- Medications which may impact the results of the endotoxin challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics).
- Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 2 weeks.
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 |
|---|---|---|
| Clinical Center Reference Endotoxin (CCRE)Also: LPSInhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE) | Biological | CCRE |
Primary outcome
Neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU),
Time frame: 0-24 hours post challenge
1 secondary outcome
changes in PFT's and vital signs
Time frame: 0-21 days post challenge
Results and safety
The study was stopped early (reason given: no further funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2012.
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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.
David B Peden, MD, MS principal investigator
University of North Carolina at Chapel Hill, Dept of Pediatrics / Center for Environmental Medicine, Asthma and Lung Biology
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 Clinical Center Reference Endotoxin (CCRE) in people with Healthy Controls, run by University of North Carolina, Chapel Hill 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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 8 Oct 2012. 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 was stopped early (reason given: no further funding). Results are not available in the source record.
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?
Neutrophil response (influx of PMNs to the airways as determined in sputum) after inhalation of CCRE (20,000 EU), (time frame: 0-24 hours post challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2012.