Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia

NCT01048502 | Completed Results DMC

• 2 other identifiers: 810598P50HL083799
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Cardiovascular Disease

Keywords

healthy volunteer

Outcome Measures

Primary Outcomes (1)

• The Effect of Omega-3 Fatty Acid Supplementation on Cytokine Production (Plasma Levels of TNFα) During an in Vivo Inflammatory Challenge (LPS).

  randomization and 8 weeks post

Secondary Outcomes (1)

• Changes in Inflammatory Parameter (Plasma TNF-α Levels) After Treatment With Fenofibrate or Placebo.

  baseline and 6-8 weeks

Study Arms (4)

Fenofibrate (Tricor) (145 mg/day)

EXPERIMENTAL

Participants will be given 1 fenofibrate (Tricor) 145mg and 4 fish oil placebos - supplies of study drug will be provided to last 8 weeks.

Drug: Fenofibrate (Tricor) tablets

Placebo

PLACEBO COMPARATOR

Participants will be given 5 placebo pills (4 fish oil placebo and 1 fenofibrate placebo) - supplies of study drug will be provided to last 8 weeks.

Drug: Placebo

Lovaza (900 mg/day)

EXPERIMENTAL

Participants will be given 1 Lovaza capsule, 3 Fish oil placebo capsules, and 1 Fenofibrate placebo - supplies of study drug will be provided to last 8 weeks.

Drug: Lovaza

Lovaza (3,600 mg/day)

EXPERIMENTAL

Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 8 weeks.

Drug: Lovaza

Interventions

Fenofibrate (Tricor) tablets DRUG

One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks

Fenofibrate (Tricor) (145 mg/day)

Placebo DRUG

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

Placebo

Lovaza DRUG

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.

Lovaza (3,600 mg/day); Lovaza (900 mg/day)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Clinical and Translational Research Center (CTRC); Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Ferguson JF, Xue C, Hu Y, Li M, Reilly MP. Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans. J Nutr Biochem. 2016 Apr;30:126-32. doi: 10.1016/j.jnutbio.2015.12.010. Epub 2016 Jan 11.

  PMID: 27012629 DERIVED

• Mulvey CK, Ferguson JF, Tabita-Martinez J, Kong S, Shah RY, Patel PN, Master SR, Usman MH, Propert KJ, Shah R, Mehta NN, Reilly MP. Peroxisome Proliferator-Activated Receptor-alpha Agonism With Fenofibrate Does Not Suppress Inflammatory Responses to Evoked Endotoxemia. J Am Heart Assoc. 2012 Aug;1(4):e002923. doi: 10.1161/JAHA.112.002923. Epub 2012 Aug 24.

  PMID: 23130172 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Fenofibrate; Tablets; Omacor

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Muredach Reilly
• Organization: UPenn

muredach@mail.med.upenn.edu

215-573-1214

Study Officials

• Muredach P Reilly, MB, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 13, 2010
• Study Start: January 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: February 19, 2016
• Results First Posted: February 19, 2016

Record last verified: 2016-01

Locations

US (1)