Study to Evaluate the Effect of Simvastatin, Losartan and Pioglitazone on Patients With Peripheral Arterial Disease. (LEAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00720577
Recruitment Status : Completed
First Posted : July 23, 2008
Last Update Posted : July 23, 2008
FoxHollow Technologies
Merck Sharp & Dohme Corp.
Information provided by:

Brief Summary:
Part A. The purpose of this study is to assess the effects of 6 weeks of treatment with, simvastatin, losartan or pioglitazone compared to placebo on the RNA expression profile of lower extremity peripheral arterial atherosclerotic plaque. Part B. The effect of simvastatin, losartan or pioglitazone compared to placebo on protein and lipid biomarkers in lower extremity peripheral arterial atherosclerotic plaque.

Condition or disease Intervention/treatment Phase
Peripheral Arterial Disease Drug: Simvastatin Drug: Losartan Drug: Pioglitazone Early Phase 1

Detailed Description:
This is a multi-center, randomized, double-blind, placebo-controlled, 6 week study. The study consists of 3 separate sub-studies in which patients undergoing bilateral lower extremity peripheral artery atherectomy will receive one of three FDA approved drugs known to have beneficial effect on the risk of cardiovascular disease. Patients will be selected for the particular sub-study based on a series of entry criteria and then randomized to the particular agent or placebo for 6-weeks.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Two-Part,Multicenter,Randomized,Double-Blind,Placebo-Controlled,Study to Evaluate the Effect of Simvastatin,Losartan,and Pioglitazone on Cardiovascular Disease Biomarkers in Lower Extremity Atherosclerotic Plaque Excised From Patients w/PAD
Study Start Date : December 2005
Actual Primary Completion Date : July 2007
Actual Study Completion Date : August 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1 Drug: Simvastatin
40 Mg. tablet, 1 tablet daily
Other Name: HMG-CoA reductase

Active Comparator: 2 Drug: Losartan
50 mg., tablets, 1 tablet once daily
Other Name: Cozaar

Active Comparator: 3 Drug: Pioglitazone
30 mg, tablet, 1 tablet once daily
Other Name: Systematic (IUPAC)

Primary Outcome Measures :
  1. Evaluate RNA expression profiles, protein and lipid biomarkers, and gene expression profiling on pts receiving simvastatin, losartan or pioglitazone. [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Evaluate plaque characteristics in 3 patient subsets and Left and Right extremity comparisons. [ Time Frame: 6 weeks ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men and women =90 years of age.
  • Bilateral lower extremity PAD requiring revascularization. Both extremities must have at least 1denovo atherosclerotic lesion
  • Able to space bilateral atherectomy procedures by at least 6 weeks.
  • Willing to provide informed consent to participation in genetic studies.
  • Simvastatin Substudy
  • LDL-C >100 mg/dL and <250 mg/dL TG<350 mg/dL
  • Not currently receiving or having taken a statin (simvastatin, lovastatin, rosuvastatin, atorvastatin, or pravastatin) or a combination product containing a statin for the previous 3 months.
  • Losartan Substudy
  • Diagnosis of hypertension with systolic blood pressure >120 mm Hg but <160 mm Hg, and diastolic blood pressure >80 mm Hg but <100 mm Hg.
  • Not currently receiving or having taken an ACEi or ARB.
  • Pioglitazone Substudy
  • Type II diabetes mellitus
  • HbA1c >5.5% and < 8.5%
  • Otherwise on a stable glucose lowering regimen where no changes are expected in oral regimen, or where no changes in insulin doses of more than 10 U are expected.
  • Not currently receiving or having taken a thiazolidinedione (rosiglitazone or pioglitazone) or a combination product containing a thiazolidinedione or the previous 12 months.

Exclusion Criteria:

  • Patient is pregnant, breast-feeding, or expecting to conceive during the study including the 14-day post study follow-up.
  • current condition, therapy, lab abnormality, mental legal incapacitation that in the investigator's judgment might confound the results of the study.
  • Patient is currently participating in or has participated in a study with an investigational compound within 30 days of Visit 1.
  • Patient has donated and/or received blood (including phlebotomy of >300 mL) within 2 months prior to study.
  • Surgery or significant trauma within 2 months prior to Visit 1.
  • Patient is a user of recreational or illicit drugs or has had a recent history <1yr drug/alcohol abuse>2 alcoholic drinks per day).
  • Patient was <80% compliant with dosing during the placebo run-in period AND, in the opinion of the investigator, believed to be unable to maintain at least an 80% compliance with dosing during the active study dosing period.
  • Patient has history of myocardial infarction, stroke, coronary artery bypass surgery or other coronary, carotid, or cerebral revascularization procedure,unstable angina, or angioplasty within 1 month of Visit 1. - Patient has chronic heart failure defined by New York Heart Association NYHA) Classes III or IV.
  • Known clinically significant AV conduction disturbances or arrhythmias
  • Patient has unstable hypertension (e.g., sitting systolic blood pressure >160 mm Hg or diastolic >100 mm Hg) at Visit 1.
  • Any known clinically important bleeding or platelet disorder.
  • Patient has history of ileal bypass, gastric bypass, other significant condition associated with malabsorption.
  • Patient is HIV or hepatitis B positive.
  • Patients with significantly elevated TSH at Visit 1 may be entered after consultation with and approval by the SPONSOR. Patients with a history of hypothyroidism, who are on a stable dose of thyroxine with normal TSH level at Visit 1 may be included.
  • Patients on cyclical estrogen medications (Estrogen Replacement Therapy ERT] or oral contraceptives). Patients on non-cyclical estrogen replacement therapy or Selective Estrogen Receptor Modulator (SERM) may be included, but must be on a stable dose for at least 8 weeks prior.
  • Patients with active neoplastic disease which compromises their general health, or who currently require chemotherapy or radiation therapy, or who have completed chemotherapy or radiation therapy within 3 months prior.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00720577

Sponsors and Collaborators
FoxHollow Technologies
Merck Sharp & Dohme Corp.
Principal Investigator: David Kandzari, MD Duke University

Responsible Party: Neil Hattangadi M.D. , Vice President, Molecular Programs, FoxHollow Technologies ( Ev3) Identifier: NCT00720577     History of Changes
Other Study ID Numbers: FHT-P-05-005
First Posted: July 23, 2008    Key Record Dates
Last Update Posted: July 23, 2008
Last Verified: July 2008

Keywords provided by ev3:
Peripheral Arterial Disease
Lower extremity peripheral arterial atherosclerotic plaque
RNA Expression
Lipid Biomarkers

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Plaque, Atherosclerotic
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists