The LIMIting AAA with meTformin (LIMIT) Trial

使用二甲双胍限制 AAA (LIMIT) 试验

• 批准号: 10650132
• 负责人: RONALD L DALMAN
• 金额: $ 172.82万
• 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/10650132
• 关键词: Abdominal Aortic Aneurysm; Address; Adult; American; Analysis of Variance; Aneurysm; Aortic Aneurysm; Biological Process; Blood specimen; Cardiovascular Diseases; Cardiovascular Manifestation; Cardiovascular system; Caring; Centrifugation; Cessation of life; Clinical Trials; Computerized Medical Record; Concurrent Review; Data; Diabetes Mellitus; Diameter; Diet Modification; Disease; Disease Management; Disease Progression; Dose; Drug usage; FRAP1 gene; Goals; Growth; Health Benefit; Hematology; Human Biology; Hypoglycemic Agents; Individual; Intervention; Location; Macrophage; Medical; Medical Records; Medicare; Metabolic; Metformin; Monitor; Nuclear; Operative Surgical Procedures; Oral; Participant; Pathway interactions; Patients; Periodicals; Pharmaceutical Preparations; Physical Examination; Placebos; Prevalence; Production; Protein Family; Public Health; Quality of life; Randomized; Reactive Oxygen Species; Recommendation; Retrospective Studies; Risk; Risk Reduction; 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; non-diabetic; novel; novel therapeutic intervention; premature; prevent; primary endpoint; programs; progression risk; prospective; prospective test; repaired; resilience; response; safety assessment; 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)疾病是导致成人过早死亡的常见原因。 美国人。到目前为止，还没有医学(例如，非手术)疗法被证明在限制AAA疾病方面有效 进展，或降低AAA破裂或动脉瘤相关猝死的风险。 认识到糖尿病患者患AAA的可能性较小，当糖尿病患者出现时， 腹主动脉扩大不那么迅速，破裂不那么频繁，为医用腹主动脉疾病引入了新的可能性 管理层。最近的回顾性研究表明，世界上最常用的口服二甲双胍 降糖剂可能与AAA扩大率降低有关。然而到目前为止，这种能力 二甲双胍抑制AAA疾病的作用还没有得到科学、严格、前瞻性的评估。 根据现有的观测证据和为支持这一提议而产生的新的初步数据， 我们的基本假设是二甲双胍治疗将安全地抑制AAA疾病的进展。 糖尿病患者。为了验证这一假设，本文提出了两个具体目标。第一个目标是评估 二甲双胍在非糖尿病腹主动脉瘤患者中的耐受性和安全性。容忍度将由 连续管理生活质量调查并跟踪参与者的遵从性和保留率。安全将是 通过每半年进行一次检查、审查原始病历、补充血液学和 根据需要进行代谢小组调查。第二个目的是测试二甲双胍XR(缓释)的能力。 将现有中小型AAA的年平均扩张率降低≥30% 与安慰剂相比。为此，480名参与者将被随机分成1：1的二甲双胍或安慰剂。这个 主要终点将是24个月内平均最大正交AAA直径的增加，如 由计算机体层摄影术(CTA)确定。这些目标的成功实现将推进 对AAA病的认识以及二甲双胍治疗的翻译效用 非糖尿病患者的心血管疾病。 这些目标具体涉及NIH的战略愿景目标：1)了解人类生物学，2) 减少人类疾病，3)促进翻译研究，以及1)理解的目标 正常的生物功能和韧性，2)研究新发现的病理生物学机制，3) 开发和优化新的治疗策略来预防、治疗和治愈HLBS疾病。