Asthma
Conditions
Keywords
Asthma, airway blood flow, budesonide, glucocorticosteroid.
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).
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.
Interventions
DRUGBudesonide 360ug
A single inhaled dose of 360ug budesonide from a DPI.
DRUGBudesonide 720ug
A single inhaled dose of 720ug budesonide from a DPI.
DRUGBudesonide 1440ug
A single dose of 1440ug of the budesonide from DPI.
DRUGBudesonide720ug 4 times
720ug of budesonide will be inhaled by the subjects 4 times, separated by 30 minutes.
DRUGPlacebo
A single inhaled dose of placebo from a DPI.
Sponsors
AstraZeneca
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Airway Blood Flow (Qaw) | 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
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asthma asthmatic subject received different doses of inhaled budesonide
Budesonide: A single inhaled dose of 360ug budesonide from a DPI.
Budesonide: A single inhaled dose of 720ug budesonide from a DPI.
Budesonide: A single dose of 1440ug of the budesonide from DPI.
Budesonide: 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. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Asthma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 43 years |
| Airway blood flow | 52.3 μl/min/ml STANDARD_DEVIATION 3.5 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
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.
Time frame: participants will be followed for 6 hours after budesonide dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide 360ug | Airway Blood Flow (Qaw) | 22.3 percentage of change from baseline | Standard Error 2.1 |
| Budesonide 720ug | Airway Blood Flow (Qaw) | 29.4 percentage of change from baseline | Standard Error 2.7 |
| Budesonide 1440ug | Airway Blood Flow (Qaw) | 34.1 percentage of change from baseline | Standard Error 2.5 |
| Budesonide 720ug 4 Times | Airway Blood Flow (Qaw) | 28.2 percentage of change from baseline | Standard Error 1.9 |
| Placebo | Airway Blood Flow (Qaw) | 5.1 percentage of change from baseline | Standard Error 2.4 |
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.
Time frame: participant will be followed up to 6 hours after budesonide dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide 360ug | Forced Expiratory Volume in 1 Second (FEV1) | 0.1 percentage of change from baseline | Standard Error 0.6 |
| Budesonide 720ug | Forced Expiratory Volume in 1 Second (FEV1) | 3.2 percentage of change from baseline | Standard Error 1.9 |
| Budesonide 1440ug | Forced Expiratory Volume in 1 Second (FEV1) | 1.6 percentage of change from baseline | Standard Error 1.8 |
| Budesonide 720ug 4 Times | Forced Expiratory Volume in 1 Second (FEV1) | 3.2 percentage of change from baseline | Standard Error 2.4 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) | 0.8 percentage of change from baseline | Standard Error 2.8 |