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

May 27, 2016 updated by: Adam Wanner, University of Miami
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.

Study Overview

Status

Completed

Conditions

Intervention / 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 Type

Interventional

Enrollment (Actual)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Human Research Laboratory - University of Miami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Fluticasone
220 ug twice a day for 3 weeks
Other Names:
  • flovent
Drug: Placebo
Placebo for 3 weeks
Other Names:
  • sugar pill
Placebo Comparator: 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.
Drug: Fluticasone
220 ug twice a day for 3 weeks
Other Names:
  • flovent
Drug: Placebo
Placebo for 3 weeks
Other Names:
  • sugar pill
No Intervention: health non-smokers
The healthy non-smokers will have only visit 1 and no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Albuterol Induced Change in Qaw Before and After Fluticasone or Placebo
Time Frame: 3 weeks treatment period of ICS 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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Collaborators

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

October 6, 2010

First Submitted That Met QC Criteria

October 6, 2010

First Posted (Estimate)

October 7, 2010

Study Record Updates

Last Update Posted (Estimate)

June 29, 2016

Last Update Submitted That Met QC Criteria

May 27, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070896
  • GSK 11340 (Other Identifier: Sponsor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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