ARREST PAD (Peripheral Arterial Disease)

NCT00153166 | Completed Phase 2 Results DMC

• 2 other identifiers: 2003P-001501R01HL075771
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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.

Conditions

Arterial Occlusive Disease; Intermittent Claudication; Insulin Resistance

Keywords

peripheral arterial disease; intermittent claudication

Outcome Measures

Primary Outcomes (1)

• Lower Extremity Skeletal Muscle Glucose Uptake

  Net calf skeletal muscle glucose uptake determined by Patlak modeling.

  60 minutes

Secondary Outcomes (1)

• 'M' = Whole Body Insulin Sensitivity

  every 5 minutes for 20 minutes

Study Arms (3)

Patients with PAD (Including diabetics)

EXPERIMENTAL

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

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

PAD (Excluding Diabetics)

ACTIVE COMPARATOR

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

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

Healthy Controls

ACTIVE COMPARATOR

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

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

Interventions

atorvastatin and pioglitazone DRUG

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

Also known as: atorvastatin: lipitor, pioglitazone: actos

Healthy Controls; PAD (Excluding Diabetics); Patients with PAD (Including diabetics)

atorvastatin/placebo DRUG

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

Also known as: atorvastatin: lipitor

Healthy Controls; PAD (Excluding Diabetics); Patients with PAD (Including diabetics)

pioglitazone/placebo DRUG

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

Also known as: pioglitazone: actos

Healthy Controls; PAD (Excluding Diabetics); Patients with PAD (Including diabetics)

placebo/placebo DRUG

placebo orally three times daily

Healthy Controls; PAD (Excluding Diabetics); Patients with PAD (Including diabetics)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• week statin wash-out prior to initial study testing (if applicable)

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 25095746 DERIVED

MeSH Terms

Conditions

Arterial Occlusive Diseases; Intermittent Claudication; Insulin Resistance; Peripheral Arterial Disease

Interventions

Atorvastatin; Pioglitazone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Atherosclerosis; Arteriosclerosis

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Mark Creager
• Organization: Brigham and Women's Hospital

mcreager@partners.org

617-732-5267

Study Officials

• Mark Creager, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: January 1, 2004
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2011
• Last Updated: September 30, 2014
• Results First Posted: September 30, 2014

Record last verified: 2014-09

Locations

US (1)