ARREST PAD (Peripheral Arterial Disease)

People with peripheral arterial disease (PAD), an important clinical manifestation of
atherosclerosis, often suffer symptoms of intermittent claudication that impair their
walking ability and adversely affect their quality of life. People with PAD are also at
increased risk for adverse cardiovascular events, including myocardial infarction, stroke
and death. Unfortunately, medical therapies directed to the functional and limb-threatening
manifestations are limited. Little attention has been paid to the biologic processes that
cause PAD, and to atherogenic mechanisms that may preferentially affect the peripheral
circulation.

Vascular inflammation and insulin resistance are two important and interdependent conditions
that are associated with atherosclerosis. Subjects in this trial (160 non-diabetic adults
with stable intermittent claudication) will be randomized in a placebo-controlled, parallel
design manner, to atorvastatin 80 mg orally daily (to reduce inflammation) and pioglitazone
45 mg orally once daily (to improve insulin sensitivity). Forty healthy adult subjects, age
and gender-matched to a subset of the study group, will be enrolled to serve as a control
population. Primary and secondary study endpoints include: treadmill walking time,
endothelium-dependent vasodilation, and insulin-mediated skeletal muscle glucose uptake.