High-Density Lipoprotein (HDL) Cholesterol Increased Plaque Stabilization in the Elderly (NIA-Plaque)

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Atherosclerosis; Cardiovascular Disease	Drug: any statin; Drug: niacin; Drug: Placebo	Phase 3

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:

1. to determine the effects of statin plus placebo vs. statin plus niacin therapy on plaque size and composition,
2. 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,
3. 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	145 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	HDL Increased Plaque Stabilization in the Elderly
Study Start Date :	September 2003
Actual Primary Completion Date :	December 2008
Actual Study Completion Date :	December 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; any 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; any 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

Outcome Measures

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Primary Outcome Measures :

1. Changes in Plaque Architecture and Composition Directly Measured by Magnetic Resonance Imaging (MRI) in the Aorta and Carotid Arteries [ Time Frame: 18 months ]
   The primary endpoint is Changes in plaque architecture and composition directly measured by magnetic resonance imaging (MRI) in the aorta and carotid arteries.

Secondary Outcome Measures :

1. Multiple Combined Events ( Cardiovascular and Cerebrovascular Events as Well as Myocardial Revascularization) [ Time Frame: 18 months ]
   Cerebrovascular events (newly diagnosed) such as Stroke and Myocardial revascularization (specifically coronary artery bypass grafting, percutaneous coronary interventions, carotid endarterectomy) were recorded

Eligibility Criteria

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Ages Eligible for Study:	65 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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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:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00127218 History of Changes
Other Study ID Numbers:	NA_00035188; 5R01AG021570-03 ( U.S. NIH Grant/Contract )
First Posted:	August 5, 2005
Results First Posted:	November 9, 2015
Last Update Posted:	November 6, 2017
Last Verified:	October 2017

Keywords provided by Johns Hopkins University:

atherosclerotic plaque; MRI; inflammatory markers; statins

Additional relevant MeSH terms:

Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Atorvastatin Calcium; Rosuvastatin Calcium; Simvastatin; Pravastatin; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Niacin; Niacinamide	Nicotinic Acids; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Enzyme Inhibitors; Vasodilator Agents; Vitamin B Complex; Vitamins; Micronutrients; Growth Substances; Physiological Effects of Drugs