Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Smokers |
Drug: Fluticasone Drug: Placebo |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers |
- Flow-mediated brachial artery vasodilation [ Time Frame: 3 weeks treatment period of ICS. ] [ Designated as safety issue: No ]Flow-mediated vasodilation response in the brachial artery will be measured before, after a 3-week treatment period with ICS.
- Flow-mediated brachial vasodilation [ Time Frame: 3 weeks of placebo treatment ]Flow-mediated vasodilation response in the brachial artery will be measured before, after a 3-week treatment period with placebo.
- Flow-mediated brachial artery vasodilation [ Time Frame: 3 weeks after washout of medication ICS ] [ Designated as safety issue: No ]Flow-mediated vasodilation response in the brachial artery will be measured before, after a 3-week washout treatment period with ICS.
- changes in Airway Blood Flow (Qaw) [ Time Frame: after 3 weeks treatment with ICS ] [ Designated as safety issue: No ]Airway blood flow will be measured before and after a 3 week-treatment period with inhaled corticosteroid.
- changes in Airway blood flow [ Time Frame: 3 week treatment with matching placebo ] [ Designated as safety issue: No ]Airway blood flow will be measured before and after a 3 week-treatment period with placebo
- changes in Airway Blood Flow [ Time Frame: 3 weeks after washout of treatment ] [ Designated as safety issue: No ]Airway blood flow will be measured before and after a 3 week-treatment washout period with inhaled corticosteroid.
- inflammatory markers on blood [ Time Frame: 3 weeks of ICS treatment ] [ Designated as safety issue: No ]Inflammatory markers( IL-6 and CRP) will be measured before and after a 3 week-treatment period with inhaled corticosteroid.
- Inflammatory markers [ Time Frame: 3 week-treatment with matching placebo ] [ Designated as safety issue: No ]Inflammatory markers( IL-6 and CRP) will be measured before and after a 3 week-treatment period with placebo
- Inflammatory markers after washout period [ Time Frame: 3 weeks of ICS washout treatment ] [ Designated as safety issue: No ]Inflammatory markers( IL-6 and CRP) will be measured before and after a 3 week washout treatment of inhaled corticosteroid.
| Enrollment: | 50 |
| Study Start Date: | September 2008 |
| Study Completion Date: | September 2010 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Fluticasone effect
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.
|
Drug: Fluticasone
220 ug twice a day administered as a metered dose inhaled (MDI)
|
|
Placebo Comparator: 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.
|
Drug: Placebo
Placebo MDI
|
Detailed Description:
Cigarette smoking is associated with attenuated vascular relaxation responses in the systemic circulation. Theoretically, this defect could be related to abnormal vascular smooth muscle function or decreased stimulated endothelial NO release, a phenomenon that has been termed endothelial dysfunction.
The investigators have reported that endothelium-dependent vasodilation is blunted in the airway circulation of ex-smokers with COPD and healthy current smokers, and that treatment with an ICS reversibly restores endothelium-dependent vasodilation as assessed with inhaled albuterol. These observations raised the question if ICS could also restore endothelial function in the extrapulmonary circulation of healthy smokers.
The investigators propose to assess albuterol and nitroglycerin blood flow responses as well as flow-mediated blood flow responses in the brachial artery. The primary endpoints will be brachial artery vasodilation responses to sublingual nitroglycerin (400 µg) and flow-mediated vasodilation of the brachial artery using the reactive hyperemia test. To determine if the airway and systemic vascular response are similar, airway blood flow responses to albuterol will be assessed as well. In addition, venous blood will be obtained for serum C-reactive protein and IL-6 assays as elevations of these inflammatory markers have been associated with cardiovascular disease and reported in smokers and patients with COPD. Furthermore, these markers may be sensitive to ICS treatment.
Eligibility| Ages Eligible for Study: | 30 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Fifteen healthy current smokers with a >10 pack-year history of smoking and 15 healthy never-smokers
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.
Contacts and Locations| United States, Florida | |
| Human Research Laboratory - University of Miami | |
| Miami, Florida, United States, 33136 | |
| Principal Investigator: | Adam Wanner, MD | University of Miami |
More Information
Publications:
| Responsible Party: | Adam Wanner, MD, University of Miami |
| ClinicalTrials.gov Identifier: | NCT01216735 History of Changes |
| Other Study ID Numbers: | GSK 11340 |
| Study First Received: | October 6, 2010 |
| Last Updated: | October 6, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Miami:
|
smokers inhaled corticosteroids brachial flow airway blood flow |
albuterol spirometry endothelial dysfunction |
Additional relevant MeSH terms:
|
Fluticasone Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions |
Anti-Asthmatic Agents Respiratory System Agents Therapeutic Uses Dermatologic Agents Anti-Allergic Agents Anti-Inflammatory Agents |
ClinicalTrials.gov processed this record on May 19, 2013