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

NCT ID: NCT01216735

Last Updated: 2016-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-09-30

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.

Conditions

Tobacco Abuse Smoke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

smokers, 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) . The subjects and the investigators will be blinded to the random choice of inhaler.

Group Type: ACTIVE_COMPARATOR

Fluticasone

Intervention Type: DRUG

220 ug twice a day for 3 weeks

Placebo

Intervention Type: DRUG

Placebo for 3 weeks

smokers Placebo first, then 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.

Group Type: PLACEBO_COMPARATOR

Fluticasone

Intervention Type: DRUG

220 ug twice a day for 3 weeks

Placebo

Intervention Type: DRUG

Placebo for 3 weeks

health non-smokers

The healthy non-smokers will have only visit 1 and no intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Fluticasone

220 ug twice a day for 3 weeks

Intervention Type: DRUG

Placebo

Placebo for 3 weeks

Intervention Type: DRUG

Other Intervention Names

flovent; sugar pill

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Adam Wanner

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adam Wanner, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

Human Research Laboratory - University of Miami

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16608935 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18467553 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16414297 (View on PubMed)

Other Identifiers

GSK 11340

Identifier Type: OTHER

Identifier Source: secondary_id

20070896

Identifier Type: -

Identifier Source: org_study_id