ARREST PAD (Peripheral Arterial Disease)

Insulin Resistance Clinical Trial

Official title:

The Contribution of Inflammation and Insulin Resistance to Intermittent Claudication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00153166
• Other study ID #: 2003P-001501
• Secondary ID: R01HL075771
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 8, 2005
• Last updated: September 22, 2014
• Start date: January 2004
• Est. completion date: December 2011

Study information

• Verified date: September 2014
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00225940

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arterial Occlusive Disease
• Arterial Occlusive Diseases
• Insulin Resistance
• Intermittent Claudication
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• atorvastatin and pioglitazone
atorvastatin 80 mg orally once daily (to reduce inflammation) and pioglitazone 30 mg orally once daily (to improve insulin sensitivity)
• atorvastatin/placebo
atorvastatin 80 mg orally once daily and matching placebo orally twice daily
• pioglitazone/placebo
pioglitazone 30 mg orally once daily and matching placebo orally once daily
• placebo/placebo
placebo orally three times daily

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lower Extremity Skeletal Muscle Glucose Uptake	Net calf skeletal muscle glucose uptake determined by Patlak modeling.	60 minutes	No
Secondary	'M' = Whole Body Insulin Sensitivity	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.	every 5 minutes for 20 minutes	No