Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

• ClinicalTrials.gov Identifier: NCT01219738
• Recruitment Status: Completed
• First Posted: October 13, 2010
• Results First Posted: January 16, 2015
• Last Update Posted: January 16, 2015
• Sponsor: University of Miami
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Eliana Mendes, University of Miami

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Budesonide 360ug; Drug: Budesonide 720ug; Drug: Budesonide 1440ug; Drug: Budesonide720ug 4 times; Drug: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide
• Study Start Date: July 2008
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: budesonide 360ug; asthmatic subject received different doses of inhaled budesonide in random other	Drug: Budesonide 360ug; A single inhaled dose of 360ug budesonide from a DPI.; Other Name: Pulmicort Flexhaler
Experimental: budesonide 720ug; asthmatic subject received different doses of inhaled budesonide in random other	Drug: Budesonide 720ug; A single inhaled dose of 720ug budesonide from a DPI.; Other Name: Pulmicort Flexhaler
Experimental: budesonide 1440ug; asthmatic subject received different doses of inhaled budesonide in random other	Drug: Budesonide 1440ug; A single dose of 1440ug of the budesonide from DPI.; Other Name: Pulmicort Flexhaler
Placebo Comparator: placebo; asthmatic subject received inhaled placebo	Drug: Budesonide720ug 4 times; 720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.; Other Name: Pulmicort Flexhaler
Experimental: Budesonide720ug 4 times; asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.	Drug: Placebo; A single inhaled dose of placebo from a DPI.; Other Name: sugar pill

Outcome Measures

Primary Outcome Measures :

1. Airway Blood Flow (Qaw) [ Time Frame: participants will be followed for 6 hours after budesonide dose ]
   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.

Secondary Outcome Measures :

1. Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: participant will be followed up to 6 hours after budesonide dose ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mendes ES, Rebolledo P, Campos M, Wanner A. Immediate antiinflammatory effects of inhaled budesonide in patients with asthma. Ann Am Thorac Soc. 2014 Jun;11(5):706-11. doi: 10.1513/AnnalsATS.201307-220OC.

• Responsible Party: Eliana Mendes, University of Miami
• ClinicalTrials.gov Identifier: NCT01219738
• Other Study ID Numbers: 20071068; IRUSBUPF0002 ( Other Identifier: Sponsor )
• First Posted: October 13, 2010
• Results First Posted: January 16, 2015
• Last Update Posted: January 16, 2015
• Last Verified: January 2015

Keywords provided by Eliana Mendes, 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; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists