Asthma
Conditions
Keywords
asthma, corticosteroids, bronchodilator, airway blood flow
Brief summary
The addition of an inhaled long-acting beta-adrenergic agonist to an inhaled glucocorticosteroid improves disease control in persistent asthma. This observation has supported the use of long-acting beta-adrenergic agonist/glucocorticosteroid combination preparations for the management of asthma. Currently, salmeterol/fluticasone and formoterol/budesonide are available for clinical use. The long-term beneficial clinical effects of the two drug classes seem to be synergistic, and several mechanisms of glucocorticoid-beta-adrenergic agonist interactions involving gene transcription have been invoked to explain this phenomenon.This study, wish to address the question whether glucocorticoids can acutely potentiate the bronchodilator response to a long-acting beta-adrenergic agonist.We expect that in patients with asthma, the short-term bronchodilator effect of salmeterol is enhanced by the addition of fluticasone, which by itself has no short-term bronchodilator effect. To test this premise, we will assess the respective short-term effects of salmeterol (50 µg), fluticasone (250 µg), salmeterol/fluticasone (50/250 µg), and placebo/placebo on spirometric parameters. Airway Blood flow will also be measured to ensure that vasoconstriction does not occur.
Detailed description
Fourteen lifetime nonsmokers with a physician diagnosis of asthma will be recruited for the study. All subjects will be allowed to use short-acting beta-adrenergic agonists as rescue medication. Inclusion criteria: 1. Males and females, 18 to 65 years of age. 2. FEV1 60-85% of predicted on the screening day. Exclusion criteria: 1. Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. 2. Cardiovascular disease and/or use of cardiovascular medications 2\. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above
Interventions
DRUGfluticasone
220- mcg once
placebo inhalation once
DRUGSalmeterol
50 mcg salmeterol once
inhalation of 250 mcg of fluticasone combined with 50 mcg of salmeterol
Sponsors
GlaxoSmithKline
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females, 18 to 65 years of age. 2. FEV1 60-85% of predicted on the screening day. -
Exclusion criteria
1\. Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women. 2. Cardiovascular disease and/or use of cardiovascular medications 3. Subjects with known beta-adrenergic agonist or glucocorticosteroid intolerance 4. Acute respiratory infection within four weeks prior to the study 5. Use, within two weeks prior to the study, of any anti-asthma medication not mentioned above \-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Change From Baseline in Airway Blood Flow (Qaw) | maximum change in Qaw within 240 minutes post drug inhalation |
Participant flow
Recruitment details
Subjects were recruited from our Asthma Database. Subjects with asthma who are in our database have previously agreed to serve as potential subjects in future studies. These subjects have signed an informed consent (approved by UM IRB) to be included in this database.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants participant received in random order one of the four treatments ( fluticasone, salmeterol, fluticasone+salmeterol or placebo) | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Airway blood flow (Qaw) | 54.8 µl.min-1.ml-1 STANDARD_DEVIATION 2.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Maximum Change From Baseline in Airway Blood Flow (Qaw)
Time frame: maximum change in Qaw within 240 minutes post drug inhalation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluticasone | Maximum Change From Baseline in Airway Blood Flow (Qaw) | -11.0 change from baseline ( µl/min/ml) | Standard Error 2.9 |
| Placebo | Maximum Change From Baseline in Airway Blood Flow (Qaw) | 14.1 change from baseline ( µl/min/ml) | Standard Error 1.9 |
| Salmeterol | Maximum Change From Baseline in Airway Blood Flow (Qaw) | 23.9 change from baseline ( µl/min/ml) | Standard Error 3.6 |
| Fluticasone/Salmeterol | Maximum Change From Baseline in Airway Blood Flow (Qaw) | 25.5 change from baseline ( µl/min/ml) | Standard Error 4.7 |
Comparison: mean difference from baseline relative to placebop-value: <0.001ANOVA
Comparison: mean difference from baseline relative to placebop-value: <0.001ANOVA
Comparison: mean difference from baseline relative to placebop-value: >0.05ANOVA