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Completed

NCT Number: NCT00153166

ARREST PAD (Peripheral Arterial Disease)

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.

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Key information

Conditions

Arterial Occlusive Disease Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Intermittent Claudication Metabolic Diseases Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Peripheral Arterial Disease Peripheral Vascular Diseases Signs and Symptoms Vascular Diseases

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

atorvastatin and pioglitazone

Drug

atorvastatin 80 mg orally once daily (to reduce inflammation) and pioglitazone 30 mg orally once daily (to improve insulin sensitivity)

Other names: atorvastatin: lipitor, pioglitazone: actos

atorvastatin/placebo

Drug

atorvastatin 80 mg orally once daily and matching placebo orally twice daily

Other names: atorvastatin: lipitor

pioglitazone/placebo

Drug

pioglitazone 30 mg orally once daily and matching placebo orally once daily

Other names: pioglitazone: actos

placebo/placebo

Drug

placebo orally three times daily

Primary outcomes

  1. Lower Extremity Skeletal Muscle Glucose Uptake

    Time frame: 60 minutes

    Net calf skeletal muscle glucose uptake determined by Patlak modeling.

Secondary outcomes

  1. 'M' = Whole Body Insulin Sensitivity

    Time frame: every 5 minutes for 20 minutes

    A hyperinsulinemic-euglycemic clamp was performed prior to and during FDG-PET imaging to measure insulin sensitivity and to standardize metabolic conditions. Subjects were required to fast for 8 hours prior to the study. Patients were given a primed insulin infusion of 2 mU/kg/min. Serum glucose measurements were made at five-minute intervals from an arterialized venous sample achieved by placing the hand in a warming box at 50°C. Blood glucose levels are checked every 5 minutes and 20% dextrose infusion is adjusted to maintain a serum glucose level of approximately 80 mg/dL. Subjects were considered to have achieved steady state when the dextrose infusion rate required to maintain a serum glucose level of 80 mg/dL varied by no greater than 5%. To compute the steady-state glucose disposal rate, we averaged the glucose infusion rates over the last 20 minutes of the clamp and applied a "space correction" to account for small changes in serum glucose levels over that time period.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication

Important dates

Study start
2004
Primary completion
2010
Study completion
2011
First posted
Sep 12, 2005
Registry last updated
Sep 30, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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