Effects of Lovaza on High Density Lipoprotein (HDL) Composition and Function in Hypertriglyceridemia

• HDL cholesterol composition by density subfraction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  HDL composition by density gradient ultracentrifugation
• Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  Transaminases and glucose levels

Study hypothesis: Lovaza (purified prescription fish oil) is likely to help HDL (the "good cholesterol") work better.

Study summary: We are testing effects of Lovaza versus placebo, on various aspects of HDL and other lipoproteins, in patients with high triglyceride levels.

Study funding: This study is being funded by an investigator-initiated research grant from Glaxo Smith Kline.

• Drug: Lovaza (Omega-3 acid ethyl esters)
  1g capsules, 4 capsules po daily
  Other Name: Lovaza
• Drug: Placebo
  Placebo matching active lovaza, 1 g capsules, 4 capsules po daily

• Experimental: Lovaza
  Lovaza 4g po qd
  Intervention: Drug: Lovaza (Omega-3 acid ethyl esters)
• Placebo Comparator: Placebo
  Matching placebo
  Intervention: Drug: Placebo

Inclusion criteria:

• Fasting TG 500-2000 mg/dL (off of TG-lowering medications—see below)
• Age 35-75 years

Exclusion criteria:

• Use of Lovaza (2g/d or more) or high-dose dietary supplement omega-3 oil (4g/d or more) in the past 2 months
• Use of lipid therapy (statin, ezetimibe, fibrate, BAS, or niacin at therapeutic dose, 1g/d or higher) in the past 3 weeks (washout of prior therapy permitted)
• Anticipated need to change type or dose of BP medicine (all types allowed), of lipid-active diabetes medication (thiazolidinedione), of oral estrogen (BCP or HRT), or glucocorticoid during the study (16 + 2 weeks = 18 weeks total)
• Excess ethanol consumption (regular intake >4 drinks/d, or binges of >8 drinks at once for men, half these levels for women)
• Poorly controlled diabetes mellitus (A1c >9%)
• History of acute or chronic pancreatitis
• Use of exenatide (Byetta) or sitagliptin (Januvia), medications believed to increase the risk of acute pancreatitis
• History of significant unexplained or uncontrolled bleeding or bruising
• Poorly controlled blood pressure (>140/90mmHg, with or without treatment)
• Poorly controlled thyroid disease (TSH outside of normal range)
• Hepatic disease (ALT > 2.5x ULN, Dx of hepatitis or cirrhosis)
• Any contraindication or prior adverse reaction to Lovaza
• Active cancer (except basal cell or squamous cell skin cancer)
• Pregnancy, plan/desire to become pregnant, breast feeding
• Inability or unwillingness to provide informed consent