Effects of Niacin on Good Cholesterol in People With Peripheral Arterial Disease

The Effects of Chronic High-density Lipoprotein (HDL) Elevation With Extended Release Niacin on Peripheral Arterial Disease

Atherosclerosis is a disorder in the body that is characterized by cholesterol plaque formation in various arteries, causing narrowing of the artery and a limitation in blood flow. Depending on which artery the plaque is in, different clinical conditions occur. In adults common areas include in the heart arteries, in the neck arteries and in the aorta and lower leg arteries. When it affects the lower limbs it is known as peripheral arterial disease - PAD.

The main symptom of PAD is called "claudication" and is described as pain or discomfort in the legs when walking. The aim of PAD treatment is to improve walking distance and quality of life in those with intermittent claudication, and to decrease long term complications including illness and death.

An important controlling factor of these cholesterol plaques is a type of cholesterol called HDL (High density lipoprotein).

This study aims to look at the effect that raising HDL for a prolonged period has on blood markers of inflammation and on the cholesterol plaque composition in patients with PAD. This investigation will also have relevance to the effects of HDL elevation on plaque composition and inflammation in other areas of the body including the heart, neck and brain arteries.

Twenty (20) PAD patients with will be recruited into the study. The investigators anticipate recruitment of all 20 patients within 12 months. The 20 PAD patients all must have significant leg pains when walking, and after review by a doctor, be determined to have narrowings in the leg artery that they will plan to operate on. Patients will be randomized to either niacin (Tredaptive, 1g/day) or matching placebo for 8 weeks (prior to operation) After the 8 week period they will then go on to receive the normal interventional treatment as planned. Blood samples will be taken at enrollment and at the 8 week mark prior to surgery. The plaque that is removed at the time of operation will also be sent to the lab for analysis.

The investigators hope to show with this study that by raising the levels of HDL with extended release niacin, there are positive effects on the amount of cholesterol in the plaque, and on the markers in the blood of inflammation and thrombosis.

The hypothesis is that elevation of HDL with Niacin will have anti-atherosclerotic actions including: Lower plaque lipid content, Reduced plaque macrophage infiltration, Reduced monocyte activation, Reduced neutrophil adhesion, Inhibition of inflammation and Inhibition of thrombotic markers.

Study Overview

• Status: Terminated
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Drug: Sugar pill; Drug: Niacin/Laropiprant combination

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Baker IDI Heart and diabetes research institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age >40 years
• ankle-brachial index (ABI) of <0.9 at rest in at least one leg,
• symptom limiting intermittent claudication (unilateral or bilateral) and stable for the previous 6 months,
• superficial femoral artery disease amenable to percutaneous revascularisation,
• serum HDL <1.0 mmol/l
• a stable medication regime for at least 6 months

Exclusion Criteria:

• acute myocardial infarction or presentation with angina within 1 month of enrolment,
• serum creatinine >0.2mmol/l,
• significant co-morbidity with expected survival <6 months,
• current niacin or fibrate therapy
• unable to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Niacin / Laropiprant	Drug: Niacin/Laropiprant combination; Niacin 1g / Laropiprant 20mg for 4 weeks followed by Niacin 2g / Laropiprant 20mg for 4 weeks; Other Names: Tredaptive
Placebo Comparator: Sugar Pill (Placebo)	Drug: Sugar pill; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plaque composition	After femoral arthrectomy the excised plaque will analysed for histological studies, for lipid content, immunohistochemistry, macrophage content and size and VCAM-1 staining.	8 weeks after recruitment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Monocyte Activation	Cd11b expression on peripheral blood monocytes will be measured as a marker of monocyte activation.	8 weeks after recruitment
Plasma Neutrophil Adhesion to Immobilized Fibrinogen		8 weeks after recruitment
Platelet Aggregation Assays		8 weeks after recruitment
Plasma Thrombotic Markers		8 weeks after recruitment
Size distribution and composition of HDL		8 weeks after recruitment
Ex vivo cholesterol efflux		8 weeks after recruitment
Plasma lipid parameters and inflammatory markers	Lipid levels including total cholesterol, HDL, LDL and TGs, will be measured as well as ApoA1 protien and Plasma soluble ICAM-1 and soluble VCAM-1. TNF-A levels will also be measured and CRP.	8 weeks after recruitment

Collaborators and Investigators

• Sponsor: Bayside Health
• Collaborators: National Health and Medical Research Council, Australia
• Investigators: Principal Investigator: Bronwyn Kingwell, Bsc, PhD, Baker IDI

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: April 5, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Estimate): February 27, 2013
• Last Update Submitted That Met QC Criteria: February 25, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Peripheral arterial disease; Atherosclerosis; HDL; Niacin; Plaque; Laropiprant; High density Lipoprotein; Tredaptive; Lipid content
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Niacin
• Other Study ID Numbers: 126-11