Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Asthma Clinical Trial

Official title:

Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01219738
• Other study ID #: 20071068
• Secondary ID: IRUSBUPF0002
• Status: Completed
• Phase: N/A
• First received: October 12, 2010
• Last updated: January 7, 2015
• Start date: July 2008
• Est. completion date: August 2012

Study information

• Verified date: January 2015
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Budesonide 360ug
A single inhaled dose of 360ug budesonide from a DPI.
• Budesonide 720ug
A single inhaled dose of 720ug budesonide from a DPI.
• Budesonide 1440ug
A single dose of 1440ug of the budesonide from DPI.
• Budesonide720ug 4 times
720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.
• Placebo
A single inhaled dose of placebo from a DPI.

Locations

Country	Name	City	State
United States	Pulmonary Human Research Laboratory, University of Miami, Miller School of Medicine	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	AstraZeneca

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Airway Blood Flow (Qaw)	Qaw will be measured before and up to 6 hours 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.	participants will be followed for 6 hours after budesonide dose	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	FEV1 will be measured before and up to 6 hours 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.	participant will be followed up to 6 hours after budesonide dose	No