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

This study has been terminated.
(Tredaptive has been suspended worldwide)
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Bayside Health
ClinicalTrials.gov Identifier:
NCT01391377
First received: April 5, 2011
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Peripheral Arterial Disease
Drug: Niacin/Laropiprant combination
Drug: Sugar pill

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of Chronic High-density Lipoprotein (HDL) Elevation With Extended Release Niacin on Peripheral Arterial Disease

Resource links provided by NLM:


Further study details as provided by Bayside Health:

Primary Outcome Measures:
  • Plaque composition [ Time Frame: 8 weeks after recruitment. ] [ Designated as safety issue: No ]
    After femoral arthrectomy the excised plaque will analysed for histological studies, for lipid content, immunohistochemistry, macrophage content and size and VCAM-1 staining.


Secondary Outcome Measures:
  • Plasma Monocyte Activation [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
    Cd11b expression on peripheral blood monocytes will be measured as a marker of monocyte activation.

  • Plasma Neutrophil Adhesion to Immobilized Fibrinogen [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
  • Platelet Aggregation Assays [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
  • Plasma Thrombotic Markers [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
  • Size distribution and composition of HDL [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
  • Ex vivo cholesterol efflux [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
  • Plasma lipid parameters and inflammatory markers [ Time Frame: 8 weeks after recruitment ] [ Designated as safety issue: No ]
    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.


Enrollment: 7
Study Start Date: July 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Tredaptive
Placebo Comparator: Sugar Pill (Placebo) Drug: Sugar pill
Placebo
Other Names:
  • Placebo
  • Sugar pill

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01391377

Locations
Australia, Victoria
Baker IDI Heart and diabetes research institute
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Bayside Health
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Bronwyn Kingwell, Bsc, PhD Baker IDI
  More Information

No publications provided

Responsible Party: Bayside Health
ClinicalTrials.gov Identifier: NCT01391377     History of Changes
Other Study ID Numbers: 126-11
Study First Received: April 5, 2011
Last Updated: February 25, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council

Keywords provided by Bayside Health:
HDL
High density Lipoprotein
Peripheral arterial disease
Tredaptive
Niacin
Laropiprant
Plaque
Atherosclerosis
Lipid content

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Niacin
Nicotinic Acids
Niacinamide
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014