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

Phase 2

Withdrawn

• Conditions: COPD
• Interventions: Drug: Placebo; Drug: Fluticasone /salmeterol

• Registration Number: NCT01209715
• Lead Sponsor: University of Miami

Brief Summary

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.

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 Timeline

• Study First Submitted: 2010-09-24
• Study First Submitted QC: 2010-09-24
• Study First Posted: 2010-09-27
• Study Start: 2010-10
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-31
• Last Update Posted: 2014-08-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Fluticasone /salmeterol	Participants will be treated with placebo twice a day for 3 weeks.
Matching Placebo	Placebo	Participants will be treated with placebo twice a day for 3 weeks.
Fluticasone/salmeterol	Fluticasone /salmeterol	Participants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Miami School of Medicine; 🇺🇸 Miami, Florida, United States