Study of Soy Isoflavones in Asthma (SOYA)

大豆异黄酮治疗哮喘的研究 (SOYA)

• 批准号: 8501636
• 负责人: Lewis J Smith
• 金额: $ 10.02万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8501636
• 关键词: 12 year old; Adrenal Cortex Hormones; Animals; Antioxidants; Asthma; Biological Markers; Breathing; C-reactive protein; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Complex; Data Coordinating Center; Diet; Dietary Practices; Dietary Supplementation; Dietary intake; Disease; Drug usage; Effectiveness; Environmental Risk Factor; Epidemiology; Exhalation; Forced expiratory volume function; Genetic; Genistein; Goals; Health Care Costs; Health Services Accessibility; Healthcare; Human; In Vitro; Individual; Inflammation; Intake; Interleukin-6; Lead; Leukotriene C4; Leukotriene E4; Leukotrienes; Link; Masks; Measures; Morbidity - disease rate; Myofibroblast; Nitric Oxide; Nutrient; Outcome; Outcome Measure; Participant; Pathway interactions; Patients; Peak Expiratory Flow; Pharmaceutical Preparations; Placebo Control; Placebos; Plasma; Prevalence; Public Health; Public Health Schools; Pulmonary Function Test/Forced Expiratory Volume 1; Quality of life; Randomized; Randomized Controlled Clinical Trials; Reporting; Research Design; Respiratory physiology; Role; Severities; Severity of illness; Symptoms; Testing; United States; Vitamins; airway inflammation; cost; daidzein; dietary supplements; effective therapy; eosinophil; glycitein; health related quality of life; human study; improved; isoprostaglandin F2alpha type-III; novel; peripheral blood; primary outcome; public health relevance; research study; secondary outcome; soy; soy protein isolate; treatment response; urinary

DESCRIPTION (provided by applicant): 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.

描述(由申请人提供)： 这是针对哮喘(大豆)中大豆异黄酮类成分研究的领先临床中心的申请。它与约翰霍普金斯大学彭博公共卫生学院的罗伯特·怀斯博士提交的数据协调中心(DCC)申请有关。哮喘是一种常见疾病，对发病率和医疗费用有重大影响。尽管哮喘的患病率和严重程度在过去几十年中有所增加，但具体原因仍不清楚。一种可能的机制是改变饮食。然而，旨在确定可能导致疾病严重程度增加的关键营养素或抗氧化维生素的流行病学和干预性研究得出了不一致的结果。我们最近报道并证实了大豆染料木素摄入量低与更严重的哮喘之间的联系。我们随后发现(1)大豆异黄酮染料木素抑制了两条可能导致哮喘严重程度的关键途径，即人外周血嗜酸细胞白三烯(LT)C4合成和肌成纤维细胞分化，以及(2)大豆异黄酮补充剂减少哮喘患者呼出的一氧化氮(FeNO)和体外LTC4合成。我们现在提出一项临床试验，以检验这一新的假设，即饮食中补充大豆异黄酮是控制不佳的哮喘患者的有效治疗方法。这项研究将包括380名饮食大豆摄入量低、年龄在12岁或以上的患者，他们正在服用吸入皮质类固醇和/或白三烯调节剂，并未充分控制哮喘。参与者将被随机分配到每天100毫克的大豆异黄酮补充剂(包含染料木素、大豆苷元和大豆黄素)或安慰剂治疗6个月。主要结果指标是一秒用力呼气量(FEV1)，这是肺功能的客观指标。次要结果包括呼吸道炎症的生物标志物(FeNO，呼出的呼吸冷凝物8-异前列腺素)、哮喘症状的测量(例如，哮喘控制评分、非计划的医疗接触、生活质量)和哮喘加重。三级结果包括全身炎症的生物标志物(外周血嗜酸粒细胞计数、C反应蛋白和白细胞介素6水平)。治疗反应将与血浆金雀异黄素浓度相关。这项试验的结果将增加对饮食在哮喘中的作用的了解；可能会为哮喘患者找到一种新的、安全的和相对便宜的治疗方法；并可能对美国的公共健康产生重大影响。公共卫生相关性：这项研究的影响可能很大，因为饮食可能会影响哮喘的严重程度，而哮喘是一种常见疾病。我们小组的初步研究表明，低大豆摄入量与更严重的哮喘有关，还表明大豆异黄酮补充剂可以改善哮喘。主要的大豆异黄酮类(染料木素和大豆苷元)可以安全地作为长期补充剂服用，而且它们的成本大大低于目前大多数用于哮喘的药物治疗。