The LIMIting AAA with meTformin (LIMIT) Trial
使用二甲双胍限制 AAA (LIMIT) 试验
基本信息
- 批准号:10054902
- 负责人:
- 金额:$ 153.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-21 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:Abdominal Aortic AneurysmAddressAdultAmericanAnalysis of VarianceAneurysmAortic AneurysmBiological ProcessBlood specimenCaliberCardiovascular DiseasesCardiovascular ManifestationCardiovascular systemCaringCentrifugationCessation of lifeClinical TrialsComputerized Medical RecordConcurrent ReviewDataDiabetes MellitusDiet ModificationDiseaseDisease ManagementDisease ProgressionDoseDrug usageFRAP1 geneGoalsGrowthHealth BenefitHematologyHuman BiologyHypoglycemic AgentsIndividualInterventionLocationMedicalMedical RecordsMedicareMetabolicMetforminMonitorNuclearOperative Surgical ProceduresOralParticipantPathway interactionsPatientsPeriodicityPharmaceutical PreparationsPhysical ExaminationPlacebosPrevalenceProductionProtein FamilyPublic HealthQuality of lifeRandomizedReactive Oxygen SpeciesRetrospective StudiesRiskRuptureRuptured Abdominal Aortic AneurysmSafetySourceStratificationSudden DeathSurveysTest ResultTestingTranslational ResearchUnited States National Institutes of HealthVisionX-Ray Computed Tomographyangiogenesiscostcost estimatediabetes managementdiabeticdiabetic patientdisabilitygastrointestinalhuman diseasemacrophagenon-diabeticnovelnovel therapeuticsprematurepreventprimary endpointprogramsprospectiveprospective testrepairedresilienceresponsescreeningtheoriestreatment effect
项目摘要
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
美国人到目前为止,没有医疗(例如,非手术)治疗已证明可有效限制AAA疾病
进展,或降低AAA破裂或动脉粥样硬化相关猝死的风险。
认识到糖尿病患者不太可能出现AAA,并且当糖尿病患者出现AAA时,
AAA扩大速度较慢,破裂频率较低,为医学AAA疾病带来了新的可能性
管理最近的回顾性研究表明,二甲双胍,世界上最常用的口服
降血糖剂,可能与AAA扩大率降低有关。然而,到目前为止,
二甲双胍抑制AAA疾病的作用尚未以科学严谨的前瞻性方式进行评估。
在现有观测证据和为支持这一提议而产生的新的初步数据的基础上,
我们的基本假设是二甲双胍治疗可以安全地抑制非腹主动脉瘤患者的疾病进展,
糖尿病患者为了验证这一假设,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AAA患者中的耐受性和安全性。耐受性将由
生活质量调查的连续管理和跟踪参与者的遵守和保留。安全将是
通过半年一次的检查、原始病历审查、补充血液学检查和
根据需要进行代谢小组调查。第二个目标将检测二甲双胍XR(缓释)的能力
将现有中小型AAA的平均年扩张率降低≥ 30%
与安慰剂相比。为此,480名受试者将以1:1的比例随机分配至二甲双胍组或安慰剂组。的
主要终点将是24个月内平均最大正交AAA直径的增加,
通过计算机断层摄影术(CTA)确定。这些目标的成功实现将推动
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)推进转化研究,以及1)了解
正常的生物功能和恢复力,2)研究新发现的病理生物学机制,以及3)
开发和优化新的治疗策略,以预防、治疗和治愈HLBS疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('RONALD L DALMAN', 18)}}的其他基金
The LIMIting AAA with meTformin (LIMIT) Trial
使用二甲双胍限制 AAA (LIMIT) 试验
- 批准号:
10274809 - 财政年份:2020
- 资助金额:
$ 153.25万 - 项目类别:
The LIMIting AAA with meTformin (LIMIT) Trial
使用二甲双胍限制 AAA (LIMIT) 试验
- 批准号:
10650132 - 财政年份:2020
- 资助金额:
$ 153.25万 - 项目类别:
Mechanisms and Significance of Angiogenesis in AAA Disease
AAA 疾病中血管生成的机制和意义
- 批准号:
8228228 - 财政年份:2012
- 资助金额:
$ 153.25万 - 项目类别:
Mechanisms and Significance of Angiogenesis in AAA Disease
AAA 疾病中血管生成的机制和意义
- 批准号:
8403798 - 财政年份:2012
- 资助金额:
$ 153.25万 - 项目类别:
Critical Role of Inflammatory Macrophages in AAA Pathogenesis
炎症巨噬细胞在 AAA 发病机制中的关键作用
- 批准号:
8312534 - 财政年份:2011
- 资助金额:
$ 153.25万 - 项目类别:
Critical Role of Inflammatory Macrophages in AAA Pathogenesis
炎症巨噬细胞在 AAA 发病机制中的关键作用
- 批准号:
8179456 - 财政年份:2011
- 资助金额:
$ 153.25万 - 项目类别:
2008 Stanford AAA Summit: Strategies for Multidisciplinary Research
2008 年斯坦福 AAA 峰会:多学科研究策略
- 批准号:
7614944 - 财政年份:2008
- 资助金额:
$ 153.25万 - 项目类别:
Stanford Career Development in Vascular Medicine
斯坦福血管医学职业发展
- 批准号:
8324232 - 财政年份:2007
- 资助金额:
$ 153.25万 - 项目类别:
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