Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD

July 31, 2014 updated by: Adam Wanner, University of Miami
In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in Qaw, ΔQaw). With this approach the investigators will test the hypothesis that in stable ICS-naïve COPD patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

To test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims:

  1. To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period.
  2. To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 min after a single medium dose of an ICS (220 μg fluticasone) in stable glucocorticoid- naïve COPD patients.

For both aims, the protocol design will be placebo-controlled and double-blind. For the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. The timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ICS protocol is based on the past experience with ICS on airway vascular function. Single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ICS withdrawal (16).

Study Type

Interventional

Phase

  • Phase 2

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
        • University of Miami School of Medicine

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -Diagnosis of COPD
  • Post-bronchodilator FEV1 of less than 75% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2).
  • At entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication.

Exclusion Criteria:

  • Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
  • Use of cardiovascular medications that cannot be held on the study days
  • Use of oral airway medications or anti-inflammatory agents
  • Subjects with known beta-adrenergic agonist or NTG intolerance
  • Acute respiratory infection within four weeks prior to the study
  • 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
Placebo Comparator: Matching Placebo
Participants will be treated with placebo twice a day for 3 weeks.
Drug: Placebo
participants will be assigned to 3-weeks treatment of inhaled placebo twice a day
Drug: Fluticasone /salmeterol
Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo
Other Names:
  • Advair 250/50
Active Comparator: Fluticasone/salmeterol
Participants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks.
Drug: Fluticasone /salmeterol
Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo
Other Names:
  • Advair 250/50

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
Time Frame: 3 weeks
To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) or placebo administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week washout period.
3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.
Time Frame: 30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG
To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 minutes after a single medium dose of an ICS (220 μg fluticasone)or placebo in stable glucocorticoid-naïve COPD patients
30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG

Collaborators and Investigators

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

Sponsor

University of Miami

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

October 1, 2010

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

September 24, 2010

First Submitted That Met QC Criteria

September 24, 2010

First Posted (Estimate)

September 27, 2010

Study Record Updates

Last Update Posted (Estimate)

August 1, 2014

Last Update Submitted That Met QC Criteria

July 31, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 114279

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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