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

This study has been withdrawn prior to enrollment.
(Due to the ubiquitous use of ICS in the treatment of COPD in 2012, it was hard to find the study population.)
Sponsor:
Information provided by (Responsible Party):
Adam Wanner, University of Miami
ClinicalTrials.gov Identifier:
NCT01209715
First received: September 24, 2010
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
COPD
Drug: Placebo
Drug: Fluticasone /salmeterol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • long term effect of a glucocorticoid/long-acting beta-agonist on endothelial function in the bronchial artery. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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


Enrollment: 0
Study Start Date: October 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Advair 250/50

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01209715

Locations
United States, Florida
University of Miami School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Adam Wanner, MD University of Miami
  More Information

No publications provided

Responsible Party: Adam Wanner, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT01209715     History of Changes
Other Study ID Numbers: 114279
Study First Received: September 24, 2010
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
airway blood flow,
COPD,
endothelial dysfunction
inhaled corticosteroids

Additional relevant MeSH terms:
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Adrenergic Agents
Salmeterol
Albuterol
Adrenergic beta-Agonists
Adrenergic Agonists
Glucocorticoids
Fluticasone, salmeterol drug combination
Fluticasone
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Tocolytic Agents
Reproductive Control Agents
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 27, 2014