Conditions: Arterial Occlusive Disease Intermittent Claudication Insulin Resistance
Keywords: peripheral arterial disease intermittent claudication
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 76
Healthy volunteers: yes

Brief summary:
This trial will test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in subjects with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function.

Detailed description:
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 adults with stable intermittent claudication who are not taking insulin or insulin-sensitizing medications, such as thiazolidinediones) 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.

Arms:
arm 1: Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. arm 2: Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo. arm 3: Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.

Interventions: intervention 1: atorvastatin and pioglitazone intervention 2: atorvastatin/placebo intervention 3: pioglitazone/placebo intervention 4: placebo/placebo
Intervention descriptions: intervention 1: atorvastatin 80 mg orally once daily (to reduce inflammation) and pioglitazone 30 mg orally once daily (to improve insulin sensitivity) intervention 2: atorvastatin 80 mg orally once daily and matching placebo orally twice daily intervention 3: pioglitazone 30 mg orally once daily and matching placebo orally once daily intervention 4: placebo orally three times daily

Protocol document: