Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
University of Nebraska
Summary
Peripheral artery disease (PAD) is a manifestation of atherosclerosis that produces progressive narrowing and occlusion of the arteries supplying the lower extremities. The most common clinical manifestation of PAD is claudication, i.e., a severe functional limitation identified as gait dysfunction and walking-induced leg muscle pain relieved by rest. The standard therapies for claudication include the medications cilostazol and pentoxifylline, supervised exercise therapy and operative revascularization. Recent data demonstrated that 24 weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor Ramipril produces improvements in the walking performance of patients with claudication that are higher than those of cilostazol and pentoxifylline and similar to those produced by supervised exercise therapy and operative revascularization. The mechanisms by which Ramipril therapy produces this impressive improvement in the functional capacity of claudicating patients remain unknown. The Investigators hypothesize that treatment of claudicating PAD patients with Ramipril will improve walking performance and quality of life by improving the myopathy of the gastrocnemius. Improved myopathy is a consequence of reduced oxidative damage, reduced TGF-β1 production by vascular smooth muscle cells and reduced collagen deposition in the affected gastrocnemius.
Description
This is an interventional study of PAD patients that exhibit claudication. The purpose of this study is to determine the potential mechanisms by which Ramipril vastly improves the walking performance of these patients. The study will be achieved through these specific aims: Specific Aim #1: Test the hypothesis that Ramipril-mediated improvements of walking parameters among patients with PAD correlate with improvements in both the morphometrics and biochemistry of myofibers in the gastrocnemius of the impaired limb. Specific Aim #2: Test the hypothesis that Ramipril-mediated improvements of w…
Eligibility
- Age range
- 18–90 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. A positive history of chronic claudication, 2. Exercise-limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon, 3. Arterial occlusive disease per ankle Brachial index measurements and/or other imaging modalities, 4. Stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks. Exclusion Criteria: 1. Rest pain or tissue loss due to PAD (Fontaine stage III and IV), 2. acute lower extremity ischemic event secondary to thromboemb…
Interventions
- DrugRamipril
Ramipril therapy will start at 2.5mg/day for 1 week. Then 5mg/day for 1 week and will be increased to 10mg/day by the third week. The patients will stay on Ramipril 10mg/day for 22 weeks.
Location
- VA Medical CenterOmaha, Nebraska