Acute Effect of Mometasone on Beta-adrenergic Airway and Airway Vascular Relaxation in Severe Asthma
Information source: University of Miami
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: Mometasone 200 mcg (Drug); placebo (Drug); mometasone 400 mcg (Drug)
Sponsored by: University of Miami
Official(s) and/or principal investigator(s):
Adam Wanner, Principal Investigator, Affiliation: University of Miami
Glucocorticosteroids inhibit the disposal of organic cations by blocking organic cation
transporters expressed by non-neuronal cells, thereby interfering with the inactivation of
the organic cations by intracellular enzymes. Beta2-adrenergic agonists are organic cations,
and the concentration of inhaled beta2-adrenergic agonists at beta2-adrenergic receptor
sites on smooth muscle is likely to be increased by inhaled glucocorticosteroids (ICS) by
the ICS' effect on the glucocorticosteroid-sensitive organic cation transporters. The
investigators have shown in human airway vascular smooth muscle cells that the
glucocorticosteroid action on organic cation uptake occurs within minutes, does not involve
gene transcription or protein synthesis, is not mediated through classical steroid
receptors, and is cell membrane-linked.
In the present proposal, the investigators wish to use different single doses of
mometasone, a clinically effective ICS, administered with or at different times before
albuterol inhalation in subjects with moderate persistent asthma who are obstructed at the
time of study.
With this approach the investigators will test the hypothesis that a single inhalation of
mometasone causes an acute, transient, dose-dependent potentiation of beta2-adrenergic
If the hypothesis that a single dose of mometasone acutely potentiates beta2-adrenergic
bronchodilation is correct, the results would have a significant impact on treatment
strategies involving ICSs and beta2-adrenergic agonists in patients with asthma.
Official title: Acute Effect of Mometasone Furoate DPI on Beta-adrenergic Airway and Airway Vascular Relaxation in Moderately Severe Asthma
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator)
Primary outcome: Albuterol-induced Change in FEV1
Secondary outcome: Albuterol Induced Percent Change in Qaw
Fifteen non-smokers (males and females between the ages of 18 and 65 years) with
physician-diagnosed moderate persistent asthma will be recruited for the study. The subjects
will be allowed to use inhaled controller (including ICS) and rescue medication. At study
entry, all asthmatic subjects must be clinically stable, and have a forced
pre-bronchodilator one-second expired volume (FEV1) of < 75% predicted.
Approval for the protocol will be requested from the University of Miami Institutional
Review Board. All subjects will provide written informed consent.
- Cardiovascular disease and use of cardiovascular medications
- Use of oral controller medication for asthma (methylxanthines, systemic
glucocorticosteroids, leukotriene modifiers)
- An acute respiratory infection within 4 weeks before enrollment.
Each subject will make 8 visits to the research laboratory.
Visit 1 (screening visit): On this visit, after having signed the consent form, the subjects
will perform spirometry before and 15 min after inhaling 180 µg albuterol from a HFA-MDI
using a spacer.
Visit 2-8: Subjects that qualify for the study will be asked to return for 7 more visits for
the following treatment protocols:
- Inhalation of 400 µg mometasone 30 min before inhalation of 180 µg albuterol
- Inhalation of mometasone placebo 30 min before inhalation of 180 µg albuterol
- Simultaneous inhalation of 400 µg mometasone and 180 µg albuterol
- Simultaneous inhalation of mometasone placebo and 180 µg albuterol
Systemic blood pressure, pulse, O2 saturation, spirometry and airway blood flow ( Qaw) will
be measured before mometasone or placebo inhalation, and before and 15 min after albuterol
inhalation except on the day when mometasone and albuterol are co-administered; on that day
the measurements will be made before and 15 min after the mometasone/albuterol
Minimum age: 18 Years.
Maximum age: 65 Years.
Inclusion Criteria: Fifteen non-smokers (males and females between the ages of 18 and 65
years) with physician-diagnosed moderate persistent asthma and FEV1 < 75% of predicted.
Exclusion Criteria: Cardiovascular disease and use of cardiovascular medications,
pregnancy, use of oral controller medication for asthma (methylxanthines, systemic
glucocorticosteroids, leukotriene modifiers), an acute respiratory infection within 4
weeks before enrollment
Locations and Contacts
Human Research Laboratory- University of Miami School of Medicine, Miami, Florida 33136, United States
Starting date: October 2010
Last updated: November 17, 2014