Metformin IN Asthma for overweight and obese individuals (MINA)

项目总结/摘要 在美国，2.5亿哮喘患者中有40%以上是肥胖者。肥胖个体 患有哮喘的人更有可能患上“肥胖相关性哮喘”，这是一种易于恶化的表型。 并且对治疗有抵抗力。虽然减肥是一种有效的治疗方法，但这很难实现和维持， 因此，对于这种流行的哮喘表型，几乎没有有效和特异性的治疗选择。 肥胖引起的代谢性炎症、胰岛素抵抗和糖尿病前期可能解释了一些过量的原因 肥胖相关哮喘的发病率。二甲双胍是2型糖尿病的一线治疗药物， 对待这些条件。临床前数据表明，二甲双胍可改善气道高反应性， 肥胖哮喘动物模型中的过敏性气道炎症，观察数据显示， 二甲双胍使用与哮喘加重风险之间呈负相关，表明二甲双胍可能 对哮喘和体重指数升高的患者有益。本申请的目的是 在受试者中进行一项为期6个月、随机、安慰剂对照、平行组、双中心的二甲双胍初探性试验 从贝勒医学院招募的超重和肥胖的哮喘患者 和约翰霍普金斯大学。试点RCT将确定（1）使用远程控制的研究设计的可行性 研究参与方法和（2）二甲双胍对核心患者影响的初步估计- 中心和生理结果。这些目标的完成将有助于决定继续进行一项关键的 在超重和肥胖哮喘患者中检测二甲双胍的多中心疗效RCT， 它的设计和招生策略的细节。该项目将提供解决紧急问题的调查结果 与数百万肥胖相关哮喘的美国人相关的研究优先事项。

PROJECT SUMMARY/ABSTRACT More than 40% of the 250 million people living with asthma in the United States are obese. Obese individuals with asthma are more likely to develop “obesity-associated asthma,” a phenotype that is exacerbation-prone and resistant to treatment. While weight loss is an effective treatment, this is difficult to attain and sustain, and consequently there are few effective and specific treatment options for this prevalent asthma phenotype. Obesity-induced metabolic inflammation, insulin resistance, and pre-diabetes may explain some of the excess morbidity of obesity-associated asthma. Metformin, the first-line treatment for type 2 diabetes, comprehensively treats these conditions. Preclinical data suggest that metformin improves airways hyperresponsiveness and allergic airway inflammation among animal models of obese asthma, and observational data have shown an inverse relationship between metformin use and risk of asthma exacerbation, suggesting that metformin may be beneficial among patients with asthma and elevated body mass index. The objective of this application is to conduct a pilot, six-month, randomized, placebo-controlled, parallel-arm, two-center trial of metformin among overweight and obese individuals with physician-diagnosed asthma recruited from Baylor College of Medicine and Johns Hopkins University. The pilot RCT will determine (1) feasibility of a study design that utilizes remote methods for research participation and (2) preliminary estimates of the effect of metformin on core patient- centered and physiologic outcomes. Completion of these aims will inform the decision to proceed with a pivotal multi-center efficacy RCT testing metformin among overweight and obese participants with asthma and inform specifics of its design and enrollment strategies. This project will provide findings that address an urgent research priority relevant to the millions of Americans with obesity-associated asthma.