Combined Effects of Non-statin Treatments on Apolipoprotein A-I Up-Regulation (CENTAUR): A Feasibility Study

Inclusion Criteria

• Men/women aged 18-80 years.
• Low HDL-C, adjusted for baseline statin use
• Not on statin: Men with HDL = 3.5
• Able to understand and agree to informed consent
• Women of child-bearing age must test negative on a urine pregnancy test and agree to use reliable birth control during the study and for 1 month after last dose of study drugs. Reliable methods include oral contraceptives, a barrier method, intrauterine device, partner with vasectomy, or abstinence.
• Willing to be available for study duration and follow study procedures

Exclusion Criteria

• Subjects with following lipoprotein disorders:
• Patients on high-potency lipid-lowering regimen, defined as two or more prescription lipid-altering medications (excluding fish oils) where one is a high-dose statin (40 mg/day of rosuvastatin, 80 mg/day of other approved statins). Those on combination therapy with a lower statin dose or those taking high-dose statin monotherapy (excluding fish oils) may participate. Patients will switch to atorvastatin 10 mg and/or wash off other lipid medications to participate
• LDL > 190 mg/dL
• TG > 750 mg/dL or pancreatitis from triglyceridemia, regardless of current TG levels
• Dysbetalipoproteinemia (VLDL/TG > 0.3 -AND- TG > 200 mg/dL).
• Use of non-statin lipid therapy prior to study initiation is exclusionary if (n.b. washout of non-statins is permitted):
• Niacin > 250 mg/ day within 6 weeks: Advicor, Niaspan, Niacor, Simcor, Slo-Niacin, or supplemental niacin
• Fibrates within 12 weeks: fenofibrate (Antara, Lofibra, Tricor, Triglide), gemfibrozil (Lopid), or clofibrate
• Enterically active drugs within 4 weeks: colestipol, cholestyramine, colesevelam, ezetimibe, orlistat.
• Red yeast rice during the treatment phase of the study (i.e. must be switched to study statin)
• Fish oil > 2 g/day within 4 weeks: Lovaza (née Omacor), numerous supplements
• Altered dose of a selective estrogen receptor modulator (SERM) within 4 weeks
• Intolerance to statin, fibrate, aspirin, deuterated leucine, or niacin
• Contraindications to medications, including chronic muscle disease, history of rhabdomyolysis, moderate-severe gout, severe peptic ulcer disease, bleeding disorders, and aspirin-sensitive asthma.
• Diabetics, or fasting glucose > 110 mg/dL on two different days during screening, or use of anti-diabetic medications within 6 weeks of screening visit
• Chronic renal insufficiency, nephrotic syndrome, or current serum creatinine > 2.5 mg/dL, or GFR 2 X the upper limit of normal (ULN), albumin of 1.5 X ULN, partial thromboplastin time (PTT) > 1.5 X ULN, or current active hepatobiliary disease
• Hemoglobin (Hgb) 14 drinks/week
• Women who are pregnant, plan to conceive, or breast-feed
• Any serious or unstable medical or psychological conditions that, in investigator's opinion would compromise subject safety or successful participation.
• Currently adhering to, planning to adhere to or used within 3 months prior to screening, supplements intended for weight loss or adopt diets with aggressive carbohydrate restrictions, such as but not limited to Atkins or South Beach diets.
• Currently taking Vitamin A supplements (multivitamins allowed)(washout permitted)
• Excluded concomitant medications
• Immunosuppressants within 2 months prior to screening or are likely to require such treatment during the course of the study
• Warfarin.
• Disinclination to dairy products (e.g. inviolable dietary restrictions or lactose intolerance to an 8oz glass of milk despite lactase supplementation) Lactase supplementation is allowed during the study.
• Regular consumers of grapefruit juice, or currently taking medications metabolized by CYP 3A4 (cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone)
• History of pancreatitis or gallbladder disease
• History of coronary heart disease
• History of intolerance/adverse reaction to