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: July 11, 2012
Last verified: July 2012
  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:
  • Pain-free and maximal treadmill walking time [ Time Frame: after 3 months of study drug intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Endothelium-dependent vasodilation [ Time Frame: after 3 months of study drug intervention ] [ Designated as safety issue: No ]
  • Insulin-mediated skeletal muscle glucose utilization [ Time Frame: after 3 months of study drug intervention ] [ Designated as safety issue: No ]

Enrollment: 113
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
Active Comparator: 1 Drug: atorvastatin and pioglitazone
atorvastatin 80 mg daily and pioglitazone 45 mg daily
Other Name: Lipitor, Actos
Active Comparator: 2 Drug: atorvastatin/placebo
atorvastatin 80 mg daily and pioglitazone 45 mg daily
Active Comparator: 3 Drug: pioglitazone/placebo
atorvastatin 80 mg daily and pioglitazone 45 mg daily
Placebo Comparator: 4 Drug: placebo/placebo
placebo

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 non-diabetic adults with stable intermittent claudication) 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, RO1-HL075771
Study First Received: September 8, 2005
Last Updated: July 11, 2012
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:
Insulin Resistance
Peripheral Arterial Disease
Peripheral Vascular Diseases
Intermittent Claudication
Arterial Occlusive Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Atherosclerosis
Arteriosclerosis
Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms
Atorvastatin
Pioglitazone
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014