Study of Biomarkers of Airway Inflammation (0000-128)

Study Overview
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Brief Summary
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This study will evaluate the effects of inhaled fluticasone on cell counts and inflammatory mediators measured in sputum of healthy volunteers following exposure to inhaled lipopolysaccharide.

Official Title
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A Randomized Clinical Trial to Assess the Effects of Inhaled Fluticasone on Sputum Neutrophils After Low-dose Inhaled Endotoxin Challenge in Healthy Subjects

Conditions
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Airway Inflammation

Intervention / Treatment
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* Drug: fluticasone propionate
* Drug: Comparator: Placebo to fluticasone
* Drug: Comparator: Lipopolysaccharide (LPS)
* Drug: Comparator: albuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects who can have children must have a negative pregnancy test at screening and agree to use two methods of birth control throughout the study Male subjects with female partner(s) who can have children agree to use an acceptable method of birth control throughout the study Subject is a nonsmoker Subject is in generally good health Subject is willing to comply with the diet, alcohol, and caffeine study restrictions Exclusion Criteria: Subject is a nursing mother Subject has taken oral corticosteroids within 8 weeks or inhaled/nasal corticosteroids within 4 weeks of screening Subject has nasal polyps, recent nasal surgery, or an ongoing upper or lower respiratory tract infection Subject has a recent history of allergic rhinitis at screening Subject has any respiratory disease at screening Subject has daily phlegm or a chronic cough Subject is unable to refrain from the use of any prescription or non-prescription drugs or herbal remedies during the study Subject consumes excessive amounts of alcohol or caffeine Subject has had major surgery, or donated or lost 1 unit of blood within 4 weeks of screening Subject has a history of stroke, seizures, or major neurological disorders Subject regularly uses illicit drugs or has a history of drug/alcohol abuse Subject received a vaccination within 3 weeks of screening

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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: Comparator: Placebo to fluticasone<br>* Single dose of placebo to fluticasone (9 x 0 mcg) by metered dose inhaler in one of three treatment periods<br>Drug: Comparator: Lipopolysaccharide (LPS)<br>* 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods<br>Drug: Comparator: albuterol<br>* Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.<br>|
| Active Comparator: 2<br>Fluticasone 440 mcg | Drug: fluticasone propionate<br>* Single dose of fluticasone 440 mcg (2 x 220 mcg) or 1980 mcg (9 x 220 mcg) by metered dose inhaler in two of three treatment periods<br>Drug: Comparator: Lipopolysaccharide (LPS)<br>* 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods<br>Drug: Comparator: albuterol<br>* Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.<br>|
| Active Comparator: 3<br>Fluticasone 1980 mcg | Drug: fluticasone propionate<br>* Single dose of fluticasone 440 mcg (2 x 220 mcg) or 1980 mcg (9 x 220 mcg) by metered dose inhaler in two of three treatment periods<br>Drug: Comparator: Lipopolysaccharide (LPS)<br>* 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods<br>Drug: Comparator: albuterol<br>* Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum percent neutrophils |  | 6 hours following inhaled LPS challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum absolute neutrophils (per mL) |  | 6 hours following inhaled LPS challenge | 
| Sputum levels of IL1beta and IL8 |  | 6 hours following inhaled LPS challenge | 
| Sputum mRNA expression levels of CD14 and IL1beta |  | 6 hours following inhaled LPS challenge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sputum inflammatory biomarkers