Beta-2-agonists are effective in reducing airway narrowing in asthma and protecting against stimuli that produce bronchoconstriction. The combination of long-acting beta agonists (LABA) and inhaled corticosteroids (ICS) has become the most commonly used asthma controller medication class in the United States, but unfortunately, even when LABAs are added to ICS and used regularly, 58-81% of patients with asthma fail to achieve total control. Regular use of beta-agonists, both short and long-acting, reduces the ability of these agents to protect against the airway narrowing that occurs in asthma in response to bronchoconstrictor stimuli. We refer to this reduced effect as loss of bronchoprotection. In this proof of concept trial we aim to determine if alendronate, which diminishes beta-2 adrenergic receptor internalization, can reduce the loss of bronchoprotection that occurs with regular use of LABAs, even when used in combination with ICS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
78
University of Arizona College of Medicine
Tucson, Arizona, United States
University of California - San Francisco
San Francisco, California, United States
National Jewish Health
Denver, Colorado, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
University of Illinois at Chicago
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Brigham & Women's Hospital
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Wisconsin
Madison, Wisconsin, United States
Salmeterol Protected Methacholine Challenge PC20
Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.
Time frame: 8 weeks after randomization
Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density
Time frame: 8 weeks after randomization
Beta-2 Adrenergic Receptor Agonist-induced cAMP Production
Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.
Time frame: 8 weeks after randomization
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