Clinical trial NCT00153166: ARREST PAD (Peripheral Arterial Disease)
Official title: The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Arterial Occlusive Disease
Intermittent Claudication
Insulin Resistance
Keywords: peripheral arterial disease
intermittent claudication
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2005-09-12
Enrollment: 76
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lower Extremity Skeletal Muscle Glucose Uptake
timeFrame: 60 minutes
Secondary outcomes:
measure: 'M' = Whole Body Insulin Sensitivity
timeFrame: every 5 minutes for 20 minutes
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Mark Creager, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pande RL, Brown J, Buck S, Redline W, Doyle J, Plutzky J, Creager MA. Association of monocyte tumor necrosis factor alpha expression and serum inflammatory biomarkers with walking impairment in peripheral artery disease. J Vasc Surg. 2015 Jan;61(1):155-61. doi: 10.1016/j.jvs.2014.06.116. Epub 2014 Aug 2.