Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eliana Mendes, University of Miami
ClinicalTrials.gov Identifier:
NCT01219738
First received: October 12, 2010
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

Glucocorticosteroids recently have been shown to have non-genomic actions that are plasma membrane-mediated and do not require gene transcription and translation. One of these non-genomic effects is the inhibition of adrenergic agonist transport into airway vascular smooth muscle cells with an increase of adrenergic agonist concentrations at adrenergic receptor sites and enhance the physiological effects of endogenous adrenergic agonists (e.g. locally released norepinephrine from noradrenergic neurons) or exogenous adrenergic agonists (e.g. inhaled beta-adrenergic agonists).


Condition Intervention
Asthma
Drug: Budesonide
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Airway Blood Flow (Qaw) [ Time Frame: 15 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 15 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 30 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 30 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 60 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 60 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 90 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 90 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 180 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 180 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 240 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 240 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.

  • Airway Blood Flow (Qaw) [ Time Frame: 360 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    Qaw will be measured before and at 360 min after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo from a DPI, using a double-blinded randomized design on different days.


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 15 after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 15 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 30 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 30 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 60 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 60 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 90 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 90 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 180 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 180 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 240 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 240 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo

  • Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: 360 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo ] [ Designated as safety issue: No ]
    FEV1 will be measured before and at 360 minutes after a single inhaled dose of 360ug, 720ug, and 1440ug budesonide or placebo


Enrollment: 20
Study Start Date: July 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 360ug of budesonide
A single inhaled dose of 360ug of budesonide from a DPI.
Drug: Budesonide
A single inhaled dose of 360ug budesonide from a DPI.
Active Comparator: 720ug of budesonide
A single inhaled dose of 720ug of budesonide from a DPI
Drug: Budesonide
A single inhaled dose of 720ug budesonide from a DPI.
Active Comparator: 1440ug budesonide
A single inhaled dose of 1440ug budesonide from a DPI.
Drug: Budesonide
A single dose of 1440ug of the budesonide from DPI.
Active Comparator: 2880ug of budesonide
720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.
Drug: Budesonide
720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.
Placebo Comparator: Placebo
A single inhaled dose of placebo from a DPI.
Drug: Placebo
A single inhaled dose of placebo from a DPI.

Detailed Description:

Inhaled glucocorticosteroids typically are not recommended for the treatment of acute asthma attacks. This practice is based on the fact that glucocorticosteroids by themselves do not cause rapid bronchodilation. However, the acute inhibition of adrenergic agonist disposal by the non-genomic action of glucocorticosteroids could lead to bronchial vasoconstriction by locally released norepinephrine thereby decongesting the airway wall, and potentiate the bronchodilator effect of a concomitantly administered beta-adrenergic agonist through the same mechanism. The purpose of this study is to assess the vasoconstrictive effects of single and repetitive high-dose budesonide inhalations in moderate to severe asthmatics who use inhaled glucocorticosteroids regularly. As a secondary endpoint, airway inflammation and airway function will also be measured with the expectation that acute improvements in airflow might be detectable as a result of airway decongestion, notably in subjects with moderately severe asthma who have lower baseline lung function.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Twenty lifetime nonsmokers moderate or severe asthmatics; FEV1≥50 of predicted on the screening day

Exclusion Criteria:

Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women; Cardiovascular disease and/or use of cardiovascular medication; Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance; Acute respiratory infection and or acute exacerbation of asthma within four weeks prior to the study; Use of systemic glucocorticosteroids within 4 weeks prior to the study; Daily ICS dose (fluticasone or budesonide) > 500ug; Diabetes mellitus

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01219738

Locations
United States, Florida
Pulmonary Human Research Laboratory, University of Miami, Miller School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
AstraZeneca
Investigators
Principal Investigator: Eliana Mendes, MD University of Miami
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eliana Mendes, University of Miami
ClinicalTrials.gov Identifier: NCT01219738     History of Changes
Other Study ID Numbers: IRUSBUPF0002
Study First Received: October 12, 2010
Last Updated: February 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
Asthma, airway blood flow, budesonide, glucocorticosteroid.

Additional relevant MeSH terms:
Budesonide
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014