Effects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT) (NASCIT)

Effects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT)-A Randomized Controlled Trial

Dyslipidaemia is characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-c), elevated triglycerides and an increase in low density lipoprotein (LDL-c) particles, and has been unequivocally established as a most important cardiovascular risk factor. While statins are effective in reducing plasma levels of LDL-c, these drugs have only modest effects on raising HDL-c (typically by less than 10%), even with aggressive statin therapy. However, increasing evidence suggests that low HDL-c might be at least as relevant as high LDL-c in promoting the development and progression of atherosclerosis. The beneficial effect of raising HDL-c on clinical outcome has already been demonstrated by several studies.

Nicotinic acid is the most potent agent available for raising plasma levels of HDL-c by up to 29% at clinically recommended doses, and substantially lowers triglycerides and LDL-c. Furthermore, nicotinic acid is also the most potent lipid lowering agent available that reduces Lp(a), an independent marker of cardiovascular risk. In a recent study patients with coronary artery disease had a 21% increase in HDL-c and a 13% decrease in triglycerides, and these beneficial effects on lipid status may have contributed to a stabilization or regression of carotid intima-media-thickness (IMT).The impact in patients with advanced atherosclerosis like peripheral artery disease (PAD) in unknown.

The investigators hypothesized that nicotinic acid in addition to statin therapy may inhibit progression of peripheral arterial atherosclerosis. Therefore, the aim of the present randomized controlled trial is to investigate the effects of nicotinic acid (daily dose starting with 500 mg, up to 2000mg) in addition to simvastatin (40 mg daily) versus simvastatin (40mg daily) monotherapy in patients with low serum HDL-C levels and PAD with respect to changes of carotid and femoral IMT, changes of patients´ lipid status and occurrence of major adverse cardiovascular events (MACE).

Study Overview

• Status: Unknown
• Conditions: Atherosclerosis; Dyslipidemia
• Intervention / Treatment: Drug: simvastatin; Drug: Nicotinic Acid

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University Vienna
    • Contact: Renate Koppensteiner, Prof. Dr.; Phone Number: 00431404004671; Email: renate.koppensteiner@meduniwien.ac.at
    • Sub-Investigator: Martin Schillinger, Prof. Dr.
    • Sub-Investigator: Jasmin Amighi, Dr.
    • Sub-Investigator: Schila Sabeti, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PAD defined as an ABI ≤0.9 or >1.3 in patients with low serum HDL cholesterol levels (<45mg/dL in men, <55 mg/dL in women)

Exclusion Criteria:

• Elevated liver enzymes (above 2 times the normal level)
• Skeletal muscle myopathy or elevated serum CK levels
• Allergy or hypersensibility to either statins or nicotinic acid
• Women of childbearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Nicotinic acid + Simvastatin	Drug: simvastatin; simvastatin 40 mg; Drug: Nicotinic Acid; daily dose starting with 500 mg, up to 2000mg
Active Comparator: 2; Simvastatin	Drug: simvastatin; simvastatin 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change of carotid and femoral IMT from baseline to 6 and 12 months follow up and occurrence of major adverse cardiovascular events (MACE)	6 and 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
changes of grey scale median (GSM) score from baseline to follow-up, and changes of serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides and lipoprotein (a).	6 and 12 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Renate Koppensteiner, Prof. Dr., Division of Angiology, Department of Internal Medicine II, Medical University Vienna

Study record dates

Study Major Dates

• Study Start: June 1, 2008

Study Registration Dates

• First Submitted: July 3, 2008
• First Submitted That Met QC Criteria: July 3, 2008
• First Posted (Estimate): July 9, 2008

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 20, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: peripheral artery disease; dyslipidemia; intima-media-thickness; progression of atherosclerosis; major cardiovascular events
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism Disorders; Peripheral Vascular Diseases; Peripheral Arterial Disease; Dyslipidemias; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Vitamins; Vitamin B Complex; Nicotinic Acids; Simvastatin; Niacinamide; Niacin
• Other Study ID Numbers: Version 1.0-2007