Clinical trial NCT01391377: Effects of Niacin on Good Cholesterol in People With Peripheral Arterial Disease
Official title: The Effects of Chronic High-density Lipoprotein (HDL) Elevation With Extended Release Niacin on Peripheral Arterial Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Peripheral Arterial Disease
Keywords: HDL
High density Lipoprotein
Peripheral arterial disease
Tredaptive
Niacin
Laropiprant
Plaque
Atherosclerosis
Lipid content
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2011-07-12
Enrollment: 7
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Plaque composition
timeFrame: 8 weeks after recruitment.
Secondary outcomes:
measure: Plasma Monocyte Activation
timeFrame: 8 weeks after recruitment
measure: Plasma Neutrophil Adhesion to Immobilized Fibrinogen
timeFrame: 8 weeks after recruitment
measure: Platelet Aggregation Assays
timeFrame: 8 weeks after recruitment
measure: Plasma Thrombotic Markers
timeFrame: 8 weeks after recruitment
measure: Size distribution and composition of HDL
timeFrame: 8 weeks after recruitment
measure: Ex vivo cholesterol efflux
timeFrame: 8 weeks after recruitment
measure: Plasma lipid parameters and inflammatory markers
timeFrame: 8 weeks after recruitment
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Baker IDI Heart and diabetes research institute
state: Victoria
Study officials:
affiliation: Baker IDI
name: Bronwyn Kingwell, Bsc, PhD
role: PRINCIPAL_INVESTIGATOR
References: