Clinical trial NCT01216735: Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers
Official title: Effect of an Inhaled Glucocorticosteroid (ICS) on Endothelial Dysfunction in Cigarette Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Abuse Smoke
Keywords: smokers
inhaled corticosteroids
brachial flow
airway blood flow
albuterol
spirometry
endothelial dysfunction
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-10-07
Enrollment: 32
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo
timeFrame: 3 weeks treatment period of ICS or placebo
Secondary outcomes:
measure: Flow-mediated Brachial Vasodilation (FMD% Peak Delta)
timeFrame: 3 weeks of treatment
Other outcomes:
Locations:
city: Miami
country: United States
facility: Human Research Laboratory - University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Adam Wanner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: 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.