ARREST PAD (Peripheral Arterial Disease)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00153166
First received: September 8, 2005
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Arterial Occlusive Disease
Intermittent Claudication
Insulin Resistance
Drug: atorvastatin and pioglitazone
Drug: atorvastatin/placebo
Drug: pioglitazone/placebo
Drug: placebo/placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Lower Extremity Skeletal Muscle Glucose Uptake [ Time Frame: 60 minutes ] [ Designated as safety issue: No ]
    Net calf skeletal muscle glucose uptake determined by Patlak modeling.


Secondary Outcome Measures:
  • 'M' = Whole Body Insulin Sensitivity [ Time Frame: every 5 minutes for 20 minutes ] [ Designated as safety issue: No ]
    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.


Enrollment: 76
Study Start Date: January 2004
Study Completion Date: December 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with PAD (Including diabetics)
Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.
Drug: atorvastatin and pioglitazone
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
Drug: atorvastatin/placebo
atorvastatin 80 mg orally once daily and matching placebo orally twice daily
Other Name: atorvastatin: lipitor
Drug: pioglitazone/placebo
pioglitazone 30 mg orally once daily and matching placebo orally once daily
Other Name: pioglitazone: actos
Drug: placebo/placebo
placebo orally three times daily
Active Comparator: PAD (Excluding Diabetics)
Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.
Drug: atorvastatin and pioglitazone
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
Drug: atorvastatin/placebo
atorvastatin 80 mg orally once daily and matching placebo orally twice daily
Other Name: atorvastatin: lipitor
Drug: pioglitazone/placebo
pioglitazone 30 mg orally once daily and matching placebo orally once daily
Other Name: pioglitazone: actos
Drug: placebo/placebo
placebo orally three times daily
Active Comparator: Healthy Controls
Randomized to either atorvastatin and pioglitazone, atorvastatin/placebo, pioglitazone/placebo, or placebo/placebo.
Drug: atorvastatin and pioglitazone
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
Drug: atorvastatin/placebo
atorvastatin 80 mg orally once daily and matching placebo orally twice daily
Other Name: atorvastatin: lipitor
Drug: pioglitazone/placebo
pioglitazone 30 mg orally once daily and matching placebo orally once daily
Other Name: pioglitazone: actos
Drug: placebo/placebo
placebo orally three times daily

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

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153166

Locations
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Mark Creager, M.D. Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Mark Alan Creager, MD, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00153166     History of Changes
Obsolete Identifiers: NCT00225940
Other Study ID Numbers: 2003P-001501, R01HL075771
Study First Received: September 8, 2005
Results First Received: April 24, 2013
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:
peripheral arterial disease
intermittent claudication

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Insulin Resistance
Intermittent Claudication
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Signs and Symptoms
Vascular Diseases
Atorvastatin
Pioglitazone
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypoglycemic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014