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

COPD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01209715
• Other study ID #: 114279
• Status: Withdrawn
• Phase: Phase 2
• First received: September 24, 2010
• Last updated: July 31, 2014
• Start date: October 2010
• Est. completion date: May 2012

Study information

• Verified date: July 2014
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 ß2 - 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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• Placebo
participants will be assigned to 3-weeks treatment of inhaled placebo twice a day
• Fluticasone /salmeterol
Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo

Locations

Country	Name	City	State
United States	University of Miami School of Medicine	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 ?Qaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week washout period.	3 weeks	No
Secondary	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 (?Qaw) 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	No