Metformin IN Asthma for overweight and obese individuals (MINA)

二甲双胍用于超重和肥胖人群的哮喘治疗 (MINA)

• 批准号: 10740950
• 负责人: MEREDITH C MCCORMACK
• 金额: $ 27.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740950
• 关键词: Address; Adherence; Adipose tissue; Adopted; Adoption; Adult; Allergic; Allergic inflammation; American; American Lung Association; Animal Model; Asthma; Blood Glucose; Body Weight; Body Weight decreased; Body mass index; Characteristics; Clinical Research; Clinical Trials; Collaborations; Confidence Intervals; Data; Diabetes Mellitus; Diagnosis; Disease; Enrollment; Futility; Glucose; Goals; Hyperinsulinism; Individual; Inflammation; Insulin Resistance; Interleukin-6; Link; Macrophage; Medicine; Metabolic; Metabolic Diseases; Metabolic Marker; Metformin; Modality; Morbidity - disease rate; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Outcome; Overweight; Participant; Patients; Persons; Pharmaceutical Preparations; Phenotype; Physicians; Physiological; Placebo Control; Population; Prediabetes syndrome; Randomized; Recording of previous events; Research Design; Research Methodology; Research Priority; Resistance; Risk; Role; Safety; Site; Telemedicine; Testing; Titrations; Transportation; United States; Universities; Visit; adherence rate; airway hyperresponsiveness; allergic airway inflammation; arm; asthma exacerbation; asthmatic patient; atopy; clinical care; cohort; college; design; effective therapy; epidemiologic data; epidemiology study; experience; improved; medication compliance; member; mouse model; obese patients; obese person; obesity-associated asthma; opportunity cost; patient oriented; people of color; pre-clinical; primary outcome; pulmonary function; pulmonary function decline; recruit; remote visit; respiratory smooth muscle; success; translational study; virtual

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.

项目概要/摘要 在美国 2.5 亿哮喘患者中，超过 40% 是肥胖者。 患有哮喘的人更有可能患上“肥胖相关哮喘”，这是一种容易恶化的表型 虽然减肥是一种有效的治疗方法，但很难实现和维持，并且 因此，针对这种流行的哮喘表型的有效且具体的治疗选择较少。 肥胖引起的代谢炎症、胰岛素抵抗和糖尿病前期可能可以解释一些过量的现象 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。 临床前数据表明，二甲双胍可以改善气道高反应性。 肥胖哮喘动物模型中的过敏性气道炎症，观察数据显示 二甲双胍的使用与哮喘恶化的风险之间呈负相关，这表明二甲双胍可能 对哮喘和体重指数升高的患者有益 该应用的目的是 对二甲双胍进行一项为期六个月、随机、安慰剂对照、平行组、两中心的试点试验 从贝勒医学院招募的患有医生诊断哮喘的超重和肥胖个体 试点随机对照试验将确定 (1) 利用远程研究设计的可行性。 研究参与方法和（2）二甲双胍对核心患者影响的初步估计 完成这些目标将有助于做出关键的决定。 超重和肥胖哮喘参与者中二甲双胍的多中心疗效 RCT 测试并提供信息 该项目将提供解决紧急问题的研究结果。 与数百万患有肥胖相关哮喘的美国人相关的研究重点。