Vascepa to Accelerate Lipoprotein Uptake and Elimination

Inclusion Criteria

• 1. Triglyceridemia, defined as:
• statin-treated TG > 200 mg/dL -and/or-
• statin-treated TG > 150 mg/dL -plus- statin-treated HDL = 4 caps daily of prescription fish oil or >= 6 caps daily of supplemental fish oil).
• TG > 500 mg/dL as the average of valid, statin-treated values 6. BMI > 40 kg/m2 7. BMI 125 mg/dL 9. Known familial lipoprotein lipase impairment or deficiency (Fredrickson Type I), Apo C II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III).
• Severe allergy to fish, unless non-allergic response to fish oil is established (n.b. most fish allergies are to the proteins as opposed to the fats, so with highly-purified oils the risk of a true allergy is remote).
• Known intolerance or contraindication to Vascepa, and if the former is unknown, known intolerance or contraindication to fish oil 12. Any surgical or medical condition that may interfere with absorption, distribution, metabolism, or excretion of EPA or DHA.
• History of extreme triglyceridemia (TG > 1000 mg/dL) or pancreatitis from triglyceridemia, regardless of whether it is currently controlled.
• Medical condition that would prohibit fasting (e.g. diagnosis of insulinoma or postabsorptive hypoglycemia).
• Significant disinclination to dairy products (e.g. lactose intolerance, inviolable dietary restrictions). All participants will receive a test dose of the fat challenge during the screening visit, which consists of heavy cream and lactase enzyme. Many people with lactose intolerance successfully avert symptoms by correcting their lactase deficiency with lactase supplements. We will allow these people to participate because we will allow them to take their preferred brand and dose of lactase supplement beyond the lactase in the fat challenge if needed. However, we still require that they are able to tolerate the test dose given during screening.
• History of a non-skin malignancy within the previous 5 years. 17. Uncontrolled thyroid disease. 18. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition.
• Major surgery within the previous 6 weeks. 20. Subjects who have undergone any organ transplant. 21. History of illicit drug use within the past 3 years, or regular alcohol use of greater than 14 drinks per week. For clarity, illicit substances are per Federal law or regulations in effect at the time of first approval of this protocol.
• Women who are breast-feeding. 23. Women of childbearing potential must have a negative urine pregnancy test at screening and baseline visits and be willing to have additional urine pregnancy tests during the study.
• Sexually active subjects (both women and men) must be willing to use a medically accepted method of contraception from screening visit until month after last dose of study drug 25. Significant or unstable medical or psychological conditions, including known or suspected personality disorders, that could compromise the subject's safety or successful participation in the study in the opinion of the investigator.
• Subject-reported history of HIV and/or use of HIV medications 27. History of symptomatic gallstone disease unless definitively treated (e.g. condition successfully treated with cholecystectomy without recurrent or residual biliary disease).
• History of bariatric surgery or other major gastrointestinal surgery associated with major disruptions to drug absorption.
• Anticipation of major surgery during the screening or treatment periods of the study 30. Participants with the following conditions will opt out of heparin exposure for lipase determinations, but will be allowed to participate in the overall protocol.
• History of intolerance or adverse reaction to therapeutic or sub-therapeutic heparin regimens 32. History of intracerebral hemorrhage 33. History of significant GI bleed, unless definitively treated without recurrence 34. Women with dysfunctional uterine bleeding 35. Ind