Acute Effect of Mometasone on Beta-adrenergic Airway and Airway Vascular Relaxation in Severe Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional

Summary: 
      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
      bronchodilation.

      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.
    

Detailed description: 
      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.

      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.

      Each subject will make 8 visits to the research laboratory.

      Procedures:

      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
      co-administration.
    

Intervention name(s): placebo; mometasone 400 mcg; mometasone 200 mcg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): placebo inhalation before albuterol.; mometasone inhalation before albuterol.; 200ug mometasone before albuterol.
Other intervention name(s): Asmanex placebo; Asmanex; Asmanex
Intervention MeSH terms: Mometasone Furoate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: asthma,; inhaled corticosteroids,; airway blood flow,; mometasone,; albuterol; spirometry