This is the application for the Lead Clinical Center for the Study of Soy Isoflavones in Asthma (SOYA). It is linked to the Data Coordinating Center (DCC) application submitted by Dr. Robert Wise from the Johns Hopkins Bloomberg School of Public Health. Asthma is a common disease that has a major impact on morbidity and health care costs. Although the prevalence and severity of asthma have increased over the last several decades, the specific causes remain unknown. One possible mechanism is a change in diet. Yet, epidemiological and interventional studies designed to identify key nutrients or antioxidant vitamins that may be responsible for the increase in disease severity have produced inconsistent results. We recently reported and have since confirmed an association between low soy genistein intake and more severe asthma. We subsequently found that (1) the soy isoflavone genistein inhibits two key pathways that may contribute to asthma severity, human peripheral blood eosinophil leukotriene (LT) C4 synthesis and myofibroblast differentiation, and (2) a soy isoflavone supplement reduces exhaled nitric oxide (FeNO) and ex vivo LTC4 synthesis in patients with inadequately controlled asthma. We now propose a clinical trial to test the novel hypothesis that dietary supplementation with soy isoflavones is an effective treatment in patients with poorly controlled asthma. The study will include 380 patients with low dietary soy intake, 12 years of age or older, who are taking inhaled corticosteroids, leukotriene modifiers, or both and have inadequately controlled asthma. Participants will be randomly assigned to treatment with either a soy isoflavone supplement (containing genistein, daidzein and glycitein) 100 mg daily or placebo for six months. The primary outcome measure is forced expiratory volume in one second (FEV1), an objective measure of lung function. Secondary outcomes include biomarkers of airway inflammation (FeNO, exhaled breath condensate 8-isoprostane), measures of asthma symptoms (e.g., asthma control scores, unscheduled health care contacts, quality of life), and asthma exacerbations. Tertiary outcomes include biomarkers of systemic inflammation (peripheral blood eosinophil counts, C-reactive protein and interleukin-6 levels). Treatment response will be correlated with plasma genistein concentrations. The results of this trial will increase understanding of the role of diet in asthma;may identify a novel, safe and relatively inexpensive treatment for patients with asthma;and potentially have a major impact on public health in the United States. Public Health Relevance: The impact of this study is potentially large because diet may influence asthma severity and asthma is a common disease. Preliminary studies from our group have shown that low intake of soy is associated with more severe asthma and also suggest that soy isoflavone supplements can improve asthma. The major soy isoflavones (genistein and daidzein) can be safely given as supplements for prolonged periods, and their cost is substantially lower than most currently used drug treatments for asthma.
The impact of this study is potentially large because diet may influence asthma severity and asthma is a common disease. Preliminary studies from our group have shown that low intake of soy is associated with more severe asthma and also suggest that soy isoflavone supplements can improve asthma. The major soy isoflavones (genistein and daidzein) can be safely given as supplements for prolonged periods, and their cost is substantially lower than most currently used drug treatments for asthma.
| Smith, Lewis J; Kalhan, Ravi; Wise, Robert A et al. (2015) Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. JAMA 313:2033-43 |
