Range of Neutrophil Response to 20,000 EU of Clinical Center Reference Endotoxin in Otherwise Healthy Smokers

Study Overview
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Brief Summary
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Endotoxin is a component of outdoor air pollution, an air contaminant found in a number of different workplaces, and is even found in homes. The endotoxin used for this study is obtained from the National Institutes of Health, and is called Clinical Center Reference Endotoxin, or CCRE. The purpose of this Phase 1 research study is to identify a dose of inhaled endotoxin that is safe (does not cause prolonged cough, shortness of breath or other problems), but causes changes in sputum cell samples that the scientists can measure. Phase 1 research studies like this one are not intended to be a treatment, but are a scientific investigation. Eventually, with these types of studies we will be able to examine why some people are more sensitive to endotoxin. Scientists at other universities have found that while most people do not have a considerable lung response to endotoxin at doses as high as 60,000 EU (endotoxin units), a few respond to as little as a total dose of 4500 EU. Our study is designed to identify if using a dose of 20,000 EU causes changes in the lung cells but does not cause symptoms in our study subjects. In our previous studies in our lab, using an endotoxin from another source, we have used higher doses (15,000 EUs) in subjects with asthma with no major problems, and we have used 10,000 EUs of CCRE in subjects who are current smokers without seeing any problems.

Detailed Description
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We are looking for people who currently smoke a minimum of a half a pack of cigarettes each day. You must not have any other health problems, be pregnant or nursing a baby, or actively trying to become pregnant or to father a child.

Official Title
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Range of Neutrophil Response to 20,000 EU of Clinical Center Reference Endotoxin in Otherwise Healthy Smokers

Conditions
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Healthy Smokers

Intervention / Treatment
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* Biological: CCRE inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: current smoker healthy Exclusion Criteria: no asthma no chronic health conditions no daily cough not pregnant or nursing a baby not actively trying to get pregnant or father a child

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Otherwise healthy smokers | Biological: CCRE inhalation<br>* 20,000 EU CCRE given as a one-time challenge<br>* Other names: CCRE (LPS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify a dose of inhaled CCRE that is well tolerated and that induces measurable increases in neutrophil content of induced sputum that can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin. |  | post exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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current, no health problems, no daily cough from smoking