Acute bronchoconstrictor and bronchodilator responses to placebo have been documented in short-term experimental exposures in selected asthmatics. However, it is not known if the often-observed improvement in asthma seen in placebo-treated patients in clinical trials is the result of non-specific factors such as better monitoring, natural disease history, or regression to the mean. If placebo effects do account for this response, then it might be possible to use strategies that improve placebo responses to improve the response to active treatments. This application proposes to conduct a multicenter clinical trial enrolling 600 participants randomly allocated to receive either placebo capsules or active drug (Montelukast, a leukotriene antagonist). Participants will be further randomized to receive their treatment either in a neutral fashion, or in a context that is crafted to increase the expectancy that the active treatment is highly effective, i.e. enhancing the """"""""meaning"""""""" inherent in the treatment. In addition to this 2 x 2 factorial design, a fifth group will be randomly allocated to receive usual care (no treatment) but will be followed with the same data collection schedule as the other groups. The primary outcome measure is peak expiratory flow. Secondary outcomes include asthma symptoms, exacerbations, quality of life, and health care use. This trial will answer the following questions: 1) Is there a true placebo response in asthma that is not due to non-specific factors? 2) Can the placebo effect in asthma be augmented by interventions that increase expectancy of benefit? 3) Can interventions that increase expectancy augment the effect of active treatment? 4) Are placebo effects additive or interactive with treatment effects? Secondary questions that will be addressed include the delineation of outcome measures that may be differentially responsive to placebo or expectancy effects; whether health beliefs and self-efficacy might identify patients susceptible to such effects; and whether beliefs and attitudes of caregivers might affect interactions with patients that influence placebo responses in asthmatics. Understanding the placebo response can lead to improvements in research and treatment of asthma.
