Clinical trial NCT00127218: High-Density Lipoprotein (HDL) Cholesterol Increased Plaque Stabilization in the Elderly
Official title: HDL Increased Plaque Stabilization in the Elderly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerosis
Cardiovascular Disease
Keywords: atherosclerotic plaque
MRI
inflammatory markers
statins
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2005-08-05
Enrollment: 145
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Changes in Plaque Architecture and Composition Directly Measured by Magnetic Resonance Imaging (MRI) in the Aorta and Carotid Arteries
timeFrame: 18 months
Secondary outcomes:
measure: Multiple Combined Events ( Cardiovascular and Cerebrovascular Events as Well as Myocardial Revascularization)
timeFrame: 18 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Unversity School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Joao AC Lima, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/s0002-9149(98)00448-2.
citation: 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. doi: 10.1161/01.cir.99.6.736.
citation: 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. doi: 10.1056/NEJMoa011090.