Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia
Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia
The purpose of this study is to better understand the anti-inflammatory benefits of two
 prescription medicines that are currently used to help people with cholesterol problems.

 Fish oil, from eating certain kinds of fish and from supplement pills, has been used to help
 control cholesterol and reduce inflammation (the body's response to injury or sickness).
 Lovaza® is the brand name for prescription strength fish oil pills. In this study, we will be
 looking at how Lovaza® works to help reduce inflammation in healthy volunteers.

 Tricor® is the brand name for prescription fenofibrate pills. Fenofibrate is a prescription
 medicine that many doctors give to people with high triglyceride (fat in the blood) levels.
 In this study, we will be looking at how Tricor® works to help reduce inflammation in healthy
 volunteers.

 Endotoxin or lipopolysaccharide (LPS) is a small part of bacteria (that is no longer living)
 that can cause many of the effects similar to bacterial infections in humans. However, it can
 be administered in very small amounts to produce a mild immune response much the same as a
 'flu' like illness. Within 1 ½ -3 hours after giving LPS by vein, a response consisting of
 fever, chills, headache, nausea and vomiting and generalized aches and pains will occur which
 lasts up to 6-8 hours. In addition to the flu like symptoms, the response causes temporary
 changes in cholesterol, triglycerides and blood sugar. Different people respond differently
 to LPS. We are using LPS in this study to bring on a temporary inflammatory response in the
 body and to compare the responses of people who receive Lovaza® or Tricor® to the responses
 of people who receive a placebo (pill that does not contain medicine).
Inclusion Criteria:

 -  Men and non-pregnant/lactating women between the ages of 18 and 45.

 -  Body Mass Index (BMI) ≥18 and ≤30

 -  Participants who are able to give written informed consent and willing to comply with
 all study-related procedures.

 Exclusion Criteria:

 -  Known clinically manifest atherosclerotic cardiovascular disease, including coronary
 disease, cerebrovascular disease, or peripheral vascular disease

 -  History of diabetes mellitus

 -  Fasting glucose >126mg/dL at screening

 -  History of a non-skin malignancy within the previous 5 years

 -  Renal insufficiency as defined by creatinine outside of lab defined normal range or
 eGFR <60 ml/Kg/min at Screening Visit

 -  History of liver disease or abnormal Liver Function Tests (LFTs) (aspartate
 aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase,
 gamma-glutamyl transpeptidase (GGT) > 1.5x upper limit of normal (ULN); bilirubin > 2x
 ULN) at Screening Visit

 -  Men who are unwilling to limit alcohol consumption to < 14 alcoholic drinks per week
 or < 4 alcoholic drinks per occasion (American Medical Association/National Institute
 on Alcohol Abuse and Alcoholism (AMA / NIAAA) criteria for "at risk" usage levels)
 while participating in the study

 -  Women who are unwilling to limit alcohol consumption to < 7 alcoholic drinks per week
 or < 3 alcoholic drinks per occasion (AMA / NIAAA criteria for "at risk" usage levels)
 while participating in the study

 -  Total white blood cell count less than or equal to 3.0 THO/uL

 -  Hemoglobin less than 11.0 g/dL

 -  Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory
 condition or minor active infection

 -  Self-reported history of HIV positive

 -  First degree family history of premature cardiovascular disease event (father or
 brother if diagnosed at before 55 years of age; mother or sister if diagnosed before
 65 years of age)

 -  Patients who have undergone any organ transplant

 -  Individuals who currently use tobacco products or have done so in the previous 30 days

 -  Treatment with aspirin, Nonsteroidal Anti-inflammatory Drugs (NSAIDs),
 cyclooxygenase-2 (COX-2) inhibitors, steroids or any immunomodulatory therapy 2 weeks
 prior to the Screening Visit

 -  Treatment with statins, fibrates or niacin 4 weeks prior to the Screening Visit.

 -  Current daily use of Vitamin C > 1000 mg, Beta carotene > 1000 IU, vitamin A > 5000
 IU, vitamin E > 400 IU, and selenium > 200 mcg

 -  Participants who are unwilling to eliminate omega-3 fatty acid (eicosapentaenoic acid
 (EPA) + docosahexaenoic acid (DHA)) supplements and/or fortified food, or have their
 usual intake of high omega-3 fish (tuna and other non-fried fish) be > 3 to 4 servings
 per month as assessed by a simple screening questionnaire

 -  Positive urine pregnancy test result.

 -  Participation in another clinical trial within the previous 6 weeks prior to the
 Screening Visit.

 -  Poorly controlled blood pressure (BP > 160/110) or on any anti-hypertensive
 medications.

 -  A diagnosis of metabolic syndrome using updated 2004 National Cholesterol Education
 Program Adult Treatment Panel III (NCEP ATPIII) criteria.

 -  Any medical condition or abnormal laboratory value that is judged clinically
 significant by an investigator