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

NCT00720577 | Completed Early Phase 1

• 1 other identifier: FHT-P-05-005
• Study Type: interventional
• Target: 164
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Peripheral Arterial Disease

Keywords

Peripheral Arterial Disease; PAD; Lower extremity peripheral arterial atherosclerotic plaque; RNA Expression; Lipid Biomarkers

Outcome Measures

Primary Outcomes (1)

• Evaluate RNA expression profiles, protein and lipid biomarkers, and gene expression profiling on pts receiving simvastatin, losartan or pioglitazone.

  6 weeks

Secondary Outcomes (1)

• Evaluate plaque characteristics in 3 patient subsets and Left and Right extremity comparisons.

  6 weeks

Study Arms (3)

1

ACTIVE COMPARATOR

Drug: Simvastatin

2

ACTIVE COMPARATOR

Drug: Losartan

3

ACTIVE COMPARATOR

Drug: Pioglitazone

Interventions

Simvastatin DRUG

40 Mg. tablet, 1 tablet daily

Also known as: HMG-CoA reductase

1

Losartan DRUG

50 mg., tablets, 1 tablet once daily

Also known as: Cozaar

2

Pioglitazone DRUG

30 mg, tablet, 1 tablet once daily

Also known as: Systematic (IUPAC)

3

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medtronic Endovascular: lead
• FoxHollow Technologies: collaborator
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Simvastatin; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; Losartan; Pioglitazone

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Hydroxymethylglutaryl CoA Reductases; 3-Hydroxyacyl CoA Dehydrogenases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Biphenyl Compounds; Benzene Derivatives; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Thiazolidinediones; Thiazoles; Sulfur Compounds

Study Officials

• David Kandzari, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2008
• First Posted: July 23, 2008
• Study Start: December 1, 2005
• Primary Completion: July 1, 2007
• Study Completion: August 1, 2007
• Last Updated: May 14, 2021

Record last verified: 2008-07