The LIMIting AAA with meTformin (LIMIT) Trial

使用二甲双胍限制 AAA (LIMIT) 试验

• 批准号: 10274809
• 负责人: RONALD L DALMAN
• 金额: $ 172.93万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10274809
• 关键词: Abdominal Aortic Aneurysm; Address; Adult; American; Analysis of Variance; Aneurysm; Aortic Aneurysm; Biological Process; Blood specimen; Caliber; Cardiovascular Diseases; Cardiovascular Manifestation; Cardiovascular system; Caring; Centrifugation; Cessation of life; Clinical Trials; Computerized Medical Record; Concurrent Review; Data; Diabetes Mellitus; Diet Modification; Disease; Disease Management; Disease Progression; Dose; Drug usage; FRAP1 gene; Goals; Growth; Health Benefit; Hematology; Human Biology; Hypoglycemic Agents; Individual; Intervention; Location; Medical; Medical Records; Medicare; Metabolic; Metformin; Monitor; Nuclear; Operative Surgical Procedures; Oral; Participant; Pathway interactions; Patients; Periodicity; Pharmaceutical Preparations; Physical Examination; Placebos; Prevalence; Production; Protein Family; Public Health; Quality of life; Randomized; Reactive Oxygen Species; Retrospective Studies; Risk; Rupture; Ruptured Abdominal Aortic Aneurysm; Safety; Source; Strategic vision; Stratification; Sudden Death; Surveys; Test Result; Testing; Translational Research; United States National Institutes of Health; X-Ray Computed Tomography; angiogenesis; cost; cost estimate; diabetes management; diabetic; diabetic patient; disability; gastrointestinal; human disease; macrophage; non-diabetic; novel; novel therapeutic intervention; premature; prevent; primary endpoint; programs; prospective; prospective test; repaired; resilience; response; screening; theories; treatment effect

Project Summary Abdominal aortic aneurysm (AAA) disease is a common cause of premature death in adult Americans. To date, no medical (e.g., non-surgical) therapies have proven effective at limiting AAA disease progression, or reducing the risk of AAA rupture or aneurysm-related sudden death. The recognition that diabetic individuals are less likely to develop AAAs and when present in diabetics, AAAs enlarge less rapidly and rupture less frequently, introduces new possibilities for medical AAA disease management. Recent retrospective studies suggest that metformin, the world’s most commonly prescribed oral hypoglycemic agent, may be associated with reduced rates of AAA enlargement. To date, however, the ability of metformin to suppress AAA disease has not been evaluated in a scientifically rigorous, prospective fashion. Building off existing observational evidence and novel preliminary data, generated to support this proposal, it is our fundamental hypothesis that metformin therapy will safely suppress AAA disease progression in non- diabetic patients. To test this hypothesis, two Specific Aims are proposed. The First Aim will evaluate the tolerability and safety of metformin in nondiabetic patients with AAA disease. Tolerance will be assessed by the serial administration of quality of life surveys and tracking participant compliance and retention. Safety will be assessed by semi-annual examinations, review of the source medical record, supplementary hematologic and metabolic panel surveys as needed. The Second Aim will test the ability of metformin XR (extended release) to reduce the average annual rate of enlargement of existing small to intermediate size AAAs by ≥ 30% compared to placebo. For this Aim, 480 participants will be randomized 1:1 to metformin or placebo. The primary endpoint will be the increase in mean maximal orthogonal AAA diameter through 24 months, as determined by computed tomographic aortography (CTA). Successful completion of these Aims will advance the understanding of AAA disease as well as the translational utility of metformin therapy to treat cardiovascular diseases in nondiabetic patients. These Aims specifically address the NIH Strategic Vision Goals of 1) understanding human biology, 2) reducing human disease, and 3) advancing translational research, as well as Objectives of 1) understanding normal biologic function and resilience, 2) investigating newly discovered pathobiological mechanisms, and 3) developing and optimizing novel therapeutic strategies to prevent, treat and cure HLBS diseases.

项目摘要 腹主动脉瘤（AAA）疾病是成人过早死亡的常见原因 美国人。迄今 进展，或降低AAA破裂或与动脉瘤相关的猝死的风险。 认识到糖尿病患者不太可能发展AAA，并且在糖尿病患者中存在时， AAAS大的速度较差，破裂的频率较低，引入了医学AAA病的新可能性 管理。最近的回顾性研究表明，二甲双胍是世界上最常见的口头规定的 降血糖剂可能与AAA膨胀率降低有关。但是，迄今为止的能力 二甲双胍以抑制AAA疾病的疾病尚未以科学严格的潜在方式进行评估。 建立现有的观察证据和新颖的初步数据，以支持该提案， 我们的基本假设是，二甲双胍疗法将安全抑制非AAA疾病进展 糖尿病患者。为了检验这一假设，提出了两个具体目标。第一个目标将评估 二甲双胍在非糖尿病患者患有AAA疾病的患者中的耐受性和安全性。公差将由 生活质量调查以及跟踪参与的依从性和保留率的连续管理。安全将是 通过半年度考试评估，审查源医疗记录，补充血液学和 代谢面板根据需要进行调查。第二个目标将测试二甲双胍XR的能力（扩展释放） 为了将现有小型至中级AAA的平均每年膨胀率降低≥30％ 与安慰剂相比。为此，将480名参与者随机分配给二甲双胍或安慰剂。这 主要终点将是平均最大正交AAA直径到24个月的增加，AS 由计算机断层学（CTA）确定。这些目标的成功完成将促进 对AAA疾病的理解以及二甲双胍治疗的转化效用 非糖尿病患者的心血管疾病。 这些目的专门针对NIH战略愿景目标1）了解人类生物学，2） 减少人类疾病，3）进行转化研究，以及目标1）理解 正常的生物学功能和弹性，2）研究新发现的病原体机制，3） 制定和优化新型的治疗策略，以预防，治疗和治愈HLBS疾病。