Acute Airway Vascular Smooth Muscle Effects of Inhaled Budesonide

University of Miami

Status: Completed

Conditions: Asthma

Treatments: Drug: Budesonide 360ug; Drug: Budesonide720ug 4 times; Drug: Placebo; Drug: Budesonide 720ug; Drug: Budesonide 1440ug

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01219738

20071068

IRUSBUPF0002 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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20 participants in 5 patient groups, including a placebo group

budesonide 360ug

Experimental group

Description:

asthmatic subject received different doses of inhaled budesonide in random other

Treatment:

Drug: Budesonide 360ug

budesonide 720ug

Experimental group

Description:

asthmatic subject received different doses of inhaled budesonide in random other

Treatment:

Drug: Budesonide 720ug

budesonide 1440ug

Experimental group

Description:

asthmatic subject received different doses of inhaled budesonide in random other

Treatment:

Drug: Budesonide 1440ug

placebo

Placebo Comparator group

Description:

asthmatic subject received inhaled placebo

Treatment:

Drug: Budesonide720ug 4 times

Budesonide720ug 4 times

Experimental group

Description:

asthmatic subject received 720ug of inhaled budesonide 4 times separated by 30 minutes.

Treatment:

Drug: Placebo