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

Phase 2WithdrawnNCT01209715

University of Miami

Overview

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.

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

Allocation

RANDOMIZED

Masking

DOUBLE

Conditions

COPD

Interventions

PlaceboDRUG

participants will be assigned to 3-weeks treatment of inhaled placebo twice a day

Fluticasone /salmeterolDRUG

Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Miami School of Medicine

Miami, Florida, United States

Outcomes

Primary Outcomes

long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.

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.

Time frame: 3 weeks

Secondary Outcomes

acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.

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

Time frame: 30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG

Data from ClinicalTrials.gov

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