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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01391377




Registration number
NCT01391377
Ethics application status
Date submitted
5/04/2011
Date registered
12/07/2011
Date last updated
27/02/2013

Titles & IDs
Public title
Effects of Niacin on Good Cholesterol in People With Peripheral Arterial Disease
Scientific title
The Effects of Chronic High-density Lipoprotein (HDL) Elevation With Extended Release Niacin on Peripheral Arterial Disease
Secondary ID [1] 0 0
126-11
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral Arterial Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Niacin/Laropiprant combination
Treatment: Drugs - Sugar pill

Active Comparator: Niacin / Laropiprant -

Placebo Comparator: Sugar Pill (Placebo) -


Treatment: Drugs: Niacin/Laropiprant combination
Niacin 1g / Laropiprant 20mg for 4 weeks followed by Niacin 2g / Laropiprant 20mg for 4 weeks

Treatment: Drugs: Sugar pill
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
8 weeks after recruitment.
Secondary outcome [1] 0 0
Plasma Monocyte Activation - Cd11b expression on peripheral blood monocytes will be measured as a marker of monocyte activation.
Timepoint [1] 0 0
8 weeks after recruitment
Secondary outcome [2] 0 0
Plasma Neutrophil Adhesion to Immobilized Fibrinogen
Timepoint [2] 0 0
8 weeks after recruitment
Secondary outcome [3] 0 0
Platelet Aggregation Assays
Timepoint [3] 0 0
8 weeks after recruitment
Secondary outcome [4] 0 0
Plasma Thrombotic Markers
Timepoint [4] 0 0
8 weeks after recruitment
Secondary outcome [5] 0 0
Size distribution and composition of HDL
Timepoint [5] 0 0
8 weeks after recruitment
Secondary outcome [6] 0 0
Ex vivo cholesterol efflux
Timepoint [6] 0 0
8 weeks after recruitment
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
8 weeks after recruitment

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Baker IDI Heart and diabetes research institute - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Bayside Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01391377
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bronwyn Kingwell, Bsc, PhD
Address 0 0
Baker IDI
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01391377