Clinical trial NCT01209715: Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD
Official title: Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COPD
Keywords: airway blood flow,
COPD,
endothelial dysfunction
inhaled corticosteroids
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2010-09-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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).

Eligibility criteria: 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

Primary outcomes:
measure: long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery.
timeFrame: 3 weeks
Secondary outcomes:
measure: acute effect of an ICS on bronchial endothelial function in stable glucocorticoid-naïve COPD patient.
timeFrame: 30 minutes and 120 minutes after inhaled albuterol and sub-lingual NTG
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
Study officials:
affiliation: University of Miami
name: Adam Wanner, MD
role: PRINCIPAL_INVESTIGATOR
References: