MEDICAL THERAPY FOR NON-OPERATIVE CANDIDATES WITH ABDOMINAL AORTIC ANEURYSMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 腹主动脉瘤(AAA)与年龄、动脉粥样硬化和主动脉壁的退行性重构有关。AAAS在老年人群中发现，在高加索男性中最常见。这种疾病的第一个症状通常是致命的破裂。一组AAA患者有令人困惑的合并症，不能进行选择性手术修复。 最近的实验室研究表明，基质金属蛋白酶(MMPs)是AAA发生、生长和破裂的主要调节因子。动物研究表明，包括四环素在内的一组抗生素是有效的基质金属蛋白酶抑制剂。四环素类药物能有效地穿透和抑制退行性人腹主动脉系统组织环境中的MMPs。强力霉素是一种四环素类药物，具有从胃肠道吸收一致、半衰期长、通过肾脏和肝脏双重代谢、良好的安全性和无已知的心血管副作用等特点，可用于临床研究抑制AAA患者的基质金属蛋白酶。 这项研究针对的是任何年龄和任何种族的成年AAA患者，他们都不是手术对象。女性将被排除在外，因为雌激素被认为在AAA调节中起到保护作用。这项研究将是一项关于多西环素在减少30名患者AAA生长方面的疗效的双盲随机对照试验。20名患者将被给予多西环素，10名患者将被给予一种看起来像这种药物的非活性药片。受试者和调查人员都不知道哪个患者被分配了活性药物或非活性化合物。在获得知情同意并指定研究编号以保密后，患者将接受基线双工超声扫描(以获得AAA大小)，然后在此后每4个月进行一次，为期一年。受试者将每月在GCRC诊所进行随访，以获得学习药物并对调查做出回应。此外，患者将在基线访问时抽取血样，然后每4个月检测一次基质金属蛋白酶水平。令人感兴趣的主要终点将是动脉瘤大小的变化和一年内基质金属蛋白酶水平的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abdominal aortic aneurysms (AAAs) are associated with aging, atherosclerosis and degenerative remodeling of the aortic wall. AAAs are found in older populations and are most common in caucasian males. The first presentation of this disease is often a fatal rupture. A subgroup of patients with AAAs have confounding comorbidities which prohibit elective operative repair. Recent laboratory investigations have pointed toward matrix metalloproteinases (MMPs) as primary modulators in AAA development, growth, and rupture. Animal studies have shown a group of antibiotics, including the tetracyclines, to be potent MMP inhibitors. Tetracyclines effectively penetrate and suppress MMPs in the tissue environment of degenerative human AAAs. Doxycycline is a tetracycline which has features attractive for clinical studies of MMP inhibition in patients with AAAs: consistent absorption from the GI tract, a long half-life, dual metabolism via the kidneys and the liver, an excellent safety profile, and no known cardiovascular side effects. This study is directed at adult patients of any age and any ethnicity with infra-renal AAAs (>5cm) who are not operative candidates. Females will be excluded as estrogens are thought to play a protective role in AAA modulation. The study will be a double blind randomized control trial of doxycycline's efficacy in reducing AAA growth in 30 patients. Twenty patients will be given doxycycline and 10 will be given an inactive pill which looks like the drug. Neither the subjects nor the investigators will know which patient has been assigned active drug or the inactive compound. After obtaining informed consent, and assigning a research number in order to maintain confidentiality, the patients will undergo a baseline duplex ultrasound scan (to obtain AAA size), then every 4 months thereafter for 1 year. Subjects will follow-up in the GCRC clinic monthly to obtain study medications and respond to a survey. Additionally, patients will have blood samples drawn at the baseline visit, then every 4 months which will be tested for MMP levels. The main endpoints of interest will be change in the size of aneurysm and change in MMP levels over a one year period.'