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.
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