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| ID | Type | Description | Link |
|---|---|---|---|
| GSK 11340 | Other Identifier | Sponsor |
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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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The hypothesis underlying the proposed study is that the blunted endothelium-dependent vasodilation seen in the airway of current smokers is also present in the brachial artery, and that the same inhaled corticosteroid (ICS) treatment regime that reversed endothelial function in the airway of current smokers will also restore endothelium-dependent relaxation in the brachial artery. Non-smokers will be used as controls and will not receive any intervention or treatment.
Cigarette smoking can lead to systemic endothelial dysfunction. Since the airway circulation is exposed to a high concentration of cigarette smoke constituents, we reasoned that airway vascular endothelial dysfunction could be present in healthy smokers without systemic endothelial dysfunction.
The purpose of this study was to compare airway and systemic endothelial function and measure markers of systemic inflammation in lung-healthy current smokers. Since endothelial dysfunction in smokers has been related to systemic inflammation, we also investigated its response to an inhaled glucocorticosteroid (ICS).
Vascular endothelial function was assessed in the airway by the airway blood-flow (Qaw) response to inhaled albuterol (ΔQaw) and in the extrapulmonary circulation by brachial arterial flow-mediated vasodilation (FMD). Venous blood was collected for C-reactive protein and IL-6.
Qaw was measured with a noninvasive inhaled soluble gas uptake technique. The uptake of the gas from the anatomical deadspace reflecting airways perfused by the airway circulation was quantitated.
Qaw was express as μL/min normalized for anatomical deadspace: μL/min/mL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| smokers, Fluticasone first, then Placebo | Active Comparator | The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI) . The subjects and the investigators will be blinded to the random choice of inhaler. |
|
| smokers Placebo first, then Fluticasone | Placebo Comparator | The current smokers will be given a 3-week treatment course of inhaled placebo MDI. The subjects and the investigators will be blinded to the random choice of inhaler. |
|
| health non-smokers | No Intervention | The healthy non-smokers will have only visit 1 and no intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluticasone | Drug | 220 ug twice a day for 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | Airway Blood flow (Qaw) will be measured before and 15 minutes after albuterol inhalation (delta Qaw). | 3 weeks treatment period of ICS or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | Flow-mediated vasodilation response in the brachial artery will be measured before and 15 minutes.after albuterol inhalation | 3 weeks of treatment |
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Inclusion Criteria:
For both healthy non-smokers and healthy current smokers:
normal spirometry Healthy current smokers: history of >10 pack-year smoking
Exclusion Criteria:
Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. Cardiovascular disease and/or use of cardiovascular medications. Subjects with known beta-adrenergic agonist or nitroglycerin intolerance. A physician diagnosis of chronic airway disease (asthma, COPD, bronchiectasis, cystic fibrosis).
Acute respiratory infection within four weeks prior to the study. Use of any airway medication. FEV1 < 80% of predicted and FEV1/FVC < 0.7. A body mass index > 30.
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| Name | Affiliation | Role |
|---|---|---|
| Adam Wanner, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Human Research Laboratory - University of Miami | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16608935 | Background | Mendes ES, Campos MA, Wanner A. Airway blood flow reactivity in healthy smokers and in ex-smokers with or without COPD. Chest. 2006 Apr;129(4):893-8. doi: 10.1378/chest.129.4.893. | |
| 18467553 | Background | Mendes ES, Horvath G, Rebolledo P, Monzon ME, Casalino-Matsuda SM, Wanner A. Effect of an inhaled glucocorticoid on endothelial function in healthy smokers. J Appl Physiol (1985). 2008 Jul;105(1):54-7. doi: 10.1152/japplphysiol.90334.2008. Epub 2008 May 8. |
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17 Non-smokers were enrolled to provide baseline measures and did not receive any intervention or treatment
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| ID | Title | Description |
|---|---|---|
| FG000 | Fluticasone First, Then Placebo | The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI) or placebo. The subjects and the investigators will be blinded to the random choice of inhaler. Fluticasone: 220 ug twice a day administered as a metered dose inhaled (MDI) or matching placebo |
| FG001 | Placebo First, Then Fluticasone | The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI) or placebo. The subjects and the investigators will be blinded to the random choice of inhaler. Fluticasone: 220 ug twice a day administered as a metered dose inhaled (MDI) or matching placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (3 Weeks) |
| |||||||||||||
| Washout (3 Weeks) |
| |||||||||||||
| Second Intervention (3 Weeks) |
|
32 participants were enrolled divided in two groups smokers and controls
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| ID | Title | Description |
|---|---|---|
| BG000 | Smokers | The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI). The subjects and the investigators will be blinded to the random choice of inhaler. Fluticasone: 220 ug twice a day administered as a metered dose inhaled (MDI) |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo | Airway Blood flow (Qaw) will be measured before and 15 minutes after albuterol inhalation (delta Qaw). | Posted | Mean | Standard Error | % change | 3 weeks treatment period of ICS or placebo |
|
The AEs were collected during the duration of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fluticasone | The current smokers will be given a 3-week treatment course of inhaled fluticasone (220 ug fluticasone twice a day administered as a MDI). The subjects and the investigators will be blinded to the random choice of inhaler. Fluticasone: 220 ug twice a day for 3 weeks Placebo: Placebo for 3 weeks |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adam Wanner, MD | University of Miami | (305) 243-2568 | awanner@med.miami.edu |
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| ID | Term |
|---|---|
| D000068298 | Fluticasone |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Placebo | Drug | Placebo for 3 weeks |
|
|
| 16414297 | Background | Wanner A, Campos MA, Mendes E. Airway blood flow reactivity in smokers. Pulm Pharmacol Ther. 2007;20(2):126-9. doi: 10.1016/j.pupt.2005.12.004. Epub 2006 Jan 18. |
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|
| NOT COMPLETED |
|
| Non-smokers |
this group served as controls for baseline data. No intervention or treatment were assigned to this group. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Airway blood flow (Qaw) | Mean | Standard Deviation | um/ml/ul |
|
|
|
| Secondary | Flow-mediated Brachial Vasodilation (FMD% Peak Delta) | Flow-mediated vasodilation response in the brachial artery will be measured before and 15 minutes.after albuterol inhalation | Posted | Mean | Standard Error | % change | 3 weeks of treatment |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Placebo | The current smokers will be given a 3-week treatment course of inhaled placebo MDI. The subjects and the investigators will be blinded to the random choice of inhaler. Fluticasone: 220 ug twice a day for 3 weeks Placebo: Placebo for 3 weeks | 0 | 15 | 0 | 15 |
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| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002241 | Carbohydrates |