Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide - Full Text View

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 noraderenergic 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:

MedlinePlus related topics: Asthma

Drug Information available for: Budesonide

U.S. FDA Resources

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

Estimated Enrollment:	20
Study Start Date:	July 2008
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (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

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

Contacts

Contact: Eliana Mendes, MD	(305) 243-2568	emendes@med.miami.edu
Contact: Adam Wanner, MD	(305) 2432568	awanner@miami.edu

Locations

United States, Florida
Pulmonary Human Research Laboratory, University of Miami, Miller School of Medicine	Recruiting
Miami, Florida, United States, 33136
Contact: Eliana Mendes, MD 305-243-2568 emendes@med.miami.edu
Contact: Adam Wanner, MD (305) 243-2568 awanner@miami.edu
Principal Investigator: Eliana Mendes, MD

Sponsors and Collaborators

University of Miami

AstraZeneca

Investigators

Principal Investigator:

Eliana Mendes, MD

University of Miami

More Information

Publications:

Horvath G, Sutto Z, Torbati A, Conner GE, Salathe M, Wanner A. Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L829-37. Epub 2003 Jun 13.

Horvath G, Lieb T, Conner GE, Salathe M, Wanner A. Steroid sensitivity of norepinephrine uptake by human bronchial arterial and rabbit aortic smooth muscle cells. Am J Respir Cell Mol Biol. 2001 Oct;25(4):500-6.

Mendes ES, Pereira A, Danta I, Duncan RC, Wanner A. Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids. Eur Respir J. 2003 Jun;21(6):989-93.

Brieva JL, Danta I, Wanner A. Effect of an inhaled glucocorticosteroid on airway mucosal blood flow in mild asthma. Am J Respir Crit Care Med. 2000 Jan;161(1):293-6.

Responsible Party:	Adam Wanner, University of Miami
ClinicalTrials.gov Identifier:	NCT01219738 History of Changes
Other Study ID Numbers:	IRUSBUPF0002
Study First Received:	October 12, 2010
Last Updated:	October 12, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:

Asthma, airway blood flow, budesonide, glucocorticosteroid.

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Bronchodilator Agents

Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 23, 2013