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

Tobacco Abuse Smoke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01216735
• Other study ID #: 20070896
• Secondary ID: GSK 11340
• Status: Completed
• Phase: N/A
• First received: October 6, 2010
• Last updated: November 26, 2014
• Start date: September 2008
• Est. completion date: September 2010

Study information

• Verified date: November 2014
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Tobacco Abuse Smoke
• Tobacco Use Disorder

Intervention

Drug:
• Fluticasone
220 ug twice a day for 3 weeks
• Placebo
Placebo for 3 weeks

Locations

Country	Name	City	State
United States	Human Research Laboratory - University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Erratum in: Chest. 2006 Jul;130(1):308. — View Citation

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. — View Citation

Wanner A, Campos MA, Mendes E. Airway blood flow reactivity in smokers. Pulm Pharmacol Ther. 2007;20(2):126-9. Epub 2006 Jan 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	3 weeks treatment period of ICS or placebo	No
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	3 weeks of treatment	No