Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers

Not Applicable

Completed

• Conditions: Tobacco Abuse Smoke
• Interventions: Drug: Fluticasone; Drug: Placebo

• Registration Number: NCT01216735
• Lead Sponsor: University of Miami

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2008-09
• Primary Completion: 2009-12
• Study Completion: 2010-09
• Study First Submitted: 2010-10-06
• Study First Submitted QC: 2010-10-06
• Study First Posted: 2010-10-07
• Results First Submitted: 2014-09-05
• Results First Submitted QC: 2014-11-26
• Results First Posted: 2014-12-05
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-27
• Last Update Posted: 2016-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
smokers, Fluticasone first, then Placebo	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) . The subjects and the investigators will be blinded to the random choice of inhaler.
smokers Placebo first, then Fluticasone	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.
smokers, Fluticasone first, then Placebo	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.
smokers Placebo first, then Fluticasone	Fluticasone	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.

Primary Outcome Measures

Name	Time	Method
Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo	3 weeks treatment period of ICS or placebo	Airway Blood flow (Qaw) will be measured before and 15 minutes after albuterol inhalation (delta Qaw).

Secondary Outcome Measures

Name	Time	Method
Flow-mediated Brachial Vasodilation (FMD% Peak Delta)	3 weeks of treatment	Flow-mediated vasodilation response in the brachial artery will be measured before and 15 minutes.after albuterol inhalation

Trial Locations

Locations (1)

Human Research Laboratory - University of Miami; 🇺🇸 Miami, Florida, United States