Ramipril Treatment of Claudication

• Status: Unknown status
• Trial end date: 2020-03-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Nebraska
• Treatments: Ramipril

Criteria

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 thromboembolic disease or acute trauma,

3. Walking capacity significantly limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology,

4. Current use of either ACE inhibitors or angiotensin II receptor blockers,

5. Chronic kidney disease with estimated Glomerular Filtration Rate < 30 ml/min/1.73 m2,

6. History of bilateral severe renal artery stenosis and 7) History of angioedema related to previous ACE-inhibitor treatment or known hypersensitivity to ramipril or other ACE inhibitors.