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

Peripheral Arterial Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01391377
• Other study ID #: 126-11
• Status: Terminated
• Phase: N/A
• First received: April 5, 2011
• Last updated: February 25, 2013
• Start date: July 2011
• Est. completion date: December 2014

Study information

• Verified date: February 2013
• Source: Bayside Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustralia: National Health and Medical Research Council
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Niacin/Laropiprant combination
Niacin 1g / Laropiprant 20mg for 4 weeks followed by Niacin 2g / Laropiprant 20mg for 4 weeks
• Sugar pill
Placebo

Locations

Country	Name	City	State
Australia	Baker IDI Heart and diabetes research institute	Melbourne	Victoria

Sponsors (2)

Lead Sponsor	Collaborator
Bayside Health	National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	Plasma Monocyte Activation	Cd11b expression on peripheral blood monocytes will be measured as a marker of monocyte activation.	8 weeks after recruitment	No
Secondary	Plasma Neutrophil Adhesion to Immobilized Fibrinogen		8 weeks after recruitment	No
Secondary	Platelet Aggregation Assays		8 weeks after recruitment	No
Secondary	Plasma Thrombotic Markers		8 weeks after recruitment	No
Secondary	Size distribution and composition of HDL		8 weeks after recruitment	No
Secondary	Ex vivo cholesterol efflux		8 weeks after recruitment	No
Secondary	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	No