ARREST PAD (Peripheral Arterial Disease)

Mass General Brigham

Status and phase: Completed; Phase 3; Phase 2

Conditions: Intermittent Claudication; Insulin Resistance; Arterial Occlusive Disease

Treatments: Drug: placebo/placebo; Drug: pioglitazone/placebo; Drug: atorvastatin and pioglitazone; Drug: atorvastatin/placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00153166

R01HL075771 (U.S. NIH Grant/Contract)

2003P-001501

Details and patient eligibility

About

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.

Full 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.

Enrollment: 76 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• symptomatic intermittent claudication for >= 6 months
• resting ankle/brachial index (ABI) <=0.90
• maximal treadmill walking time between 1-20 minutes
• >= 20% decrease in ABI post treadmill exercise
• 4 week statin wash-out prior to initial study testing (if applicable)

Exclusion criteria

• myocardial infarction or coronary artery bypass surgery within past 6 months
• lower extremity revascularization (surgical or percutaneous) within past 6 months
• transient ischemic attack or ischemic stroke within past 6 months
• pregnancy
• uncontrolled hypertension (systolic pressure > 180mmHg and/or diastolic pressure > 100mmHg
• serum creatinine >2.5
• hepatic transaminases (AST, ALT) > 3x upper limit of normal (ULN)
• creatine kinase > 5x ULN
• known hypersensitivity to HMG-CoA reductase inhibitors
• insulin dependent Type 2 diabetes
• current treatment with thiazolidinedione

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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76 participants in 3 patient groups

Patients with PAD (Including diabetics)

Experimental group

Description:

Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.

Treatment:

Drug: placebo/placebo

Drug: atorvastatin/placebo

Drug: atorvastatin and pioglitazone

Drug: pioglitazone/placebo

PAD (Excluding Diabetics)

Active Comparator group

Description:

Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.

Treatment:

Drug: placebo/placebo

Drug: atorvastatin/placebo

Drug: atorvastatin and pioglitazone

Drug: pioglitazone/placebo

Healthy Controls

Active Comparator group

Description:

Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.

Treatment:

Drug: placebo/placebo

Drug: atorvastatin/placebo

Drug: atorvastatin and pioglitazone

Drug: pioglitazone/placebo