Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia

Cardiovascular Disease Clinical Trial

— FFAME  

Official title:

Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia: The FFAME Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048502
• Other study ID #: 810598
• Secondary ID: P50HL083799
• Status: Completed
• Phase: N/A
• First received: January 11, 2010
• Last updated: January 21, 2016
• Start date: January 2010
• Est. completion date: May 2011

Study information

• Verified date: January 2016
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Endotoxemia

Intervention

Drug:
• Fenofibrate (Tricor) tablets
One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks
• Placebo
Two placebo capsules taken twice daily, morning and evening, with food and one placebo gel capsule taken once daily, in the evening, with food, for 6 to 8 weeks
• Lovaza
900 mg/day: One 900 mg capsule taken once daily, morning or evening; or 3,600 mg/day: Two 900 mg capsules taken twice daily, morning and evening; All capsules to be taken with food, for 6 to 8 weeks.

Locations

Country	Name	City	State
United States	Clinical and Translational Research Center (CTRC); Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	GlaxoSmithKline, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Effect of Omega-3 Fatty Acid Supplementation on Cytokine Production (Plasma Levels of TNFa) During an in Vivo Inflammatory Challenge (LPS).		randomization and 8 weeks post	No
Secondary	Changes in Inflammatory Parameter (Plasma TNF-a Levels) After Treatment With Fenofibrate or Placebo.		baseline and 6-8 weeks	No