High-Density Lipoprotein (HDL) Cholesterol Increased Plaque Stabilization in the Elderly - Full Text View

Sponsor:	Johns Hopkins University
Collaborator:	National Institute on Aging (NIA)
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00127218

Purpose

The purpose of this study is to investigate the added benefits of increased high-density lipoprotein (HDL) cholesterol serum levels over and above those achieved by lipid lowering therapy guided by current guidelines, in older individuals with cardiovascular disease.

Condition	Intervention	Phase
Atherosclerosis Cardiovascular Disease	Drug: any statin Drug: niacin Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	HDL Increased Plaque Stabilization in the Elderly

Resource links provided by NLM:

MedlinePlus related topics: Atherosclerosis Cholesterol Statins

Drug Information available for: Niacin Simvastatin Pravastatin Pravastatin sodium Fluvastatin Niacinamide Atorvastatin Atorvastatin calcium Rosuvastatin calcium Rosuvastatin Niacin hydrochloride

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

Changes in plaque architecture and composition directly measured by magnetic resonance imaging (MRI) in the aorta and carotid arteries [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to multiple combined events ( cardiovascular and cerebrovascular events, myocardial revascularization as well as all cause and cardiovascular death) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment:	160
Study Start Date:	September 2003
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 statin plus niacin	Drug: any statin Participants will be provided a prescription for fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily, atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily for 18 months Other Names: fluvastatin (Lescol) pravastatin (Pravachol) simvastatin (Vytorin) atorvastatin (Lipitor) rosuvastatin (Crestor) Drug: niacin long-acting niacin daily for 18 months
Placebo Comparator: 2 statin plus placebo	Drug: any statin Participants will be provided a prescription for fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily, atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily for 18 months Other Names: fluvastatin (Lescol) pravastatin (Pravachol) simvastatin (Vytorin) atorvastatin (Lipitor) rosuvastatin (Crestor) Drug: Placebo matching placebo pill daily for 18 months

Arms

Assigned Interventions

Experimental: 1

statin plus niacin

Drug: any statin

Participants will be provided a prescription for fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily, atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily for 18 months

Other Names:

fluvastatin (Lescol)
pravastatin (Pravachol)
simvastatin (Vytorin)
atorvastatin (Lipitor)
rosuvastatin (Crestor)

Drug: niacin

long-acting niacin daily for 18 months

Placebo Comparator: 2

statin plus placebo

Drug: any statin

Participants will be provided a prescription for fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily, atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily for 18 months

Other Names:

fluvastatin (Lescol)
pravastatin (Pravachol)
simvastatin (Vytorin)
atorvastatin (Lipitor)
rosuvastatin (Crestor)

Drug: Placebo

matching placebo pill daily for 18 months

Detailed Description:

The hypothesis being tested is that the current standard lipid lowering therapy, combined with a 20 percent or greater increase in serum HDL induced by long-acting niacin, reduces plaque size in older individuals with cardiovascular disease. The specific aims of testing this hypothesis are:

to determine the effects of statin plus placebo vs. statin plus niacin therapy on plaque size and composition,
to determine whether alterations of inflammatory markers of atherosclerosis induced by lipid lowering therapy parallel alterations of plaque architecture and composition in older patients with cardiovascular disease,
to determine the effects of these interventions on the incidence of cardiovascular and cerebrovascular events.

The results of the trial will be directly applicable to developing strategies for plaque stabilization in the elderly who suffer the most from the severe complications of advanced cardiovascular atherosclerosis.

A total of 144 participants aged 65 and older with cardiovascular or cerebrovascular disease will be recruited. Participants will be randomized to receive either statin plus niacin or statin plus a placebo for 18 months. Participants will be provided a prescription for fluvastatin 80 mg to be taken on a daily basis, or they may continue their ongoing or any other cholesterol-lowering drugs such as pravastatin 80 mg daily, simvastatin 20 mg daily, atorvastatin up to 20 mg daily or rosuvastatin up to 20 mg daily. Ten visits are expected, initially every 4 weeks for dose adjustment. Then visits will be every 6 months; MRI, Inflammatory Markers tests, and other lab tests will be done at baseline and the visits at months 6, 12, and 18.

Eligibility

Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Aged 65 or older
Documented clinical cardiovascular or cerebrovascular disease due to atherosclerosis
Candidate for lipid lowering therapy; no contraindication to fluvastatin, niacin or aspirin therapy
Low-density lipoprotein (LDL) cholesterol below 150 mg/dl if untreated or below 125 mg/dl on statin monotherapy
Willing to discontinue present therapy if private physician agrees with enrollment
Eligible to undergo trans-esophageal magnetic resonance imaging (MRI); no contraindications to Gadolinium-DTPA, the contrast agent used
Willing to sign Informed Consent

Exclusion Criteria:

Ineligibility for MRI procedure due to pacemaker, metal implants, or other ferromagnetic devices
Claustrophobia
Previously documented esophageal disease which would preclude trans-esophageal MRI
LDL-C greater than 150 mg/dl off lipid lowering therapy or daily statin therapy requiring doses greater than 20 mg of atorvastatin, 20 mg of simvastatin, 80 mg of lovastatin, 80 mg of pravastatin, 80 mg of extended release fluvastatin, or 20 mg of rosuvastatin
Contraindication or allergy to statins or aspirin
Current use of or known intolerance or allergy to Niaspan (a long-acting niacin)
Allergy or intolerance to Gadolinium-DTPA (MRI contrast agent)
Liver or kidney failure defined clinically and by laboratory data
Mental, neurologic or social condition preventing understanding of the rationale, procedures, risks and potential benefits associated with the trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127218

Locations

United States, Maryland
Johns Hopkins Unversity School of Medicine
Baltimore, Maryland, United States, 21218

Sponsors and Collaborators

Johns Hopkins University

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Joao AC Lima, MD, MBA

Johns Hopkins University

More Information

Publications:

Guyton JR, Goldberg AC, Kreisberg RA, Sprecher DL, Superko HR, O'Connor CM. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol. 1998 Sep 15;82(6):737-43.

Ballantyne CM, Herd JA, Ferlic LL, Dunn JK, Farmer JA, Jones PH, Schein JR, Gotto AM Jr. Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation. 1999 Feb 16;99(6):736-43.

Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001 Nov 29;345(22):1583-92.

Responsible Party:	Joao A.C. Lima, MD, MBA, Johns Hopkins University School of Medicine
ClinicalTrials.gov Identifier:	NCT00127218 History of Changes
Other Study ID Numbers:	AG0032, 5R01AG021570-03
Study First Received:	August 3, 2005
Last Updated:	August 27, 2010
Health Authority:	United States: Federal Government

Keywords provided by Johns Hopkins University:

atherosclerotic plaque
MRI
inflammatory markers
statins

Additional relevant MeSH terms:

Atherosclerosis
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Niacin
Simvastatin
Atorvastatin
Fluvastatin
Pravastatin
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
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
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012