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

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01048502
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), GlaxoSmithKline (Industry)
• Enrollment: 100
• Location: 1
• Arms: 4
• Duration (Months): 15.9
• Patients Per Site Per Month: 6.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Drug: Fenofibrate (Tricor) tablets; Drug: Placebo; Drug: Lovaza	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia: The FFAME Study
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fenofibrate (Tricor) (145 mg/day) 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; One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks
Placebo Comparator: Placebo 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; 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
Experimental: Lovaza (900 mg/day) 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; 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.
Experimental: Lovaza (3,600 mg/day) Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 8 weeks.	Drug: 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Changes in Inflammatory Parameter (Plasma TNF-α Levels) After Treatment With Fenofibrate or Placebo. [baseline and 6-8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical and Translational Research Center (CTRC); Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Muredach P Reilly, MB, MSCE, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01048502
• Other Study ID Numbers: 810598; P50HL083799
• First Posted: Jan 13, 2010
• Last Update Posted: Feb 19, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by University of Pennsylvania: healthy volunteer
• Additional relevant MeSH terms: Endotoxemia; Cardiovascular Diseases; Fenofibrate

Study Results

Participant Flow

Recruitment Details	100 subjects were enrolled; 80 completed the study.

Arm/Group Title	Fenofibrate (Tricor) (145 mg/Day)	Placebo	Lovaza (900 mg/Day)	Lovaza (3,600 mg/Day)
Arm/Group Description	Participants will be given 1 fenofibrate (Tricor) 145mg and 4 fish oil placebos - supplies of study drug will be provided to last 8 weeks. Fenofibrate (Tricor) tablets: One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks	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. 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	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. 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.	Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 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.
Period Title: Overall Study
STARTED	24	23	28	25
COMPLETED	20	16	23	21
NOT COMPLETED	4	7	5	4

Baseline Characteristics

Arm/Group Title	Fenofibrate (Tricor) (145 mg/Day)	Placebo	Lovaza (900 mg/Day)	Lovaza (3,600 mg/Day)	Total
Arm/Group Description	Participants will be given 1 fenofibrate (Tricor) 145mg and 4 fish oil placebos - supplies of study drug will be provided to last 8 weeks. Fenofibrate (Tricor)tablets: One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks	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. 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	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. 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.	Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 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.	Total of all reporting groups
Overall Participants	24	23	28	25	100
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	25.58	25.96	26.68	24.68	25.75
Sex: Female, Male (Count of Participants)
Female	11 45.8%	12 52.2%	12 42.9%	12 48%	47 47%
Male	13 54.2%	11 47.8%	16 57.1%	13 52%	53 53%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 12.5%	5 21.7%	3 10.7%	4 16%	15 15%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	5 20.8%	4 17.4%	8 28.6%	5 20%	22 22%
White	16 66.7%	14 60.9%	17 60.7%	16 64%	63 63%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Effect of Omega-3 Fatty Acid Supplementation on Cytokine Production (Plasma Levels of TNFα) During an in Vivo Inflammatory Challenge (LPS).
Time Frame	randomization and 8 weeks post

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Lovaza (900 mg/Day)	Lovaza (3,600 mg/Day)
Arm/Group Description	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. 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	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. 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.	Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 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.
Measure Participants	16	23	21
TNF-α at randomization	0.95	1.26	1.14
TNF-α 8 weeks post randomization	1.12	1.25	0.99

2. Secondary Outcome

Title	Changes in Inflammatory Parameter (Plasma TNF-α Levels) After Treatment With Fenofibrate or Placebo.
Time Frame	baseline and 6-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fenofibrate (Tricor) (145 mg/Day)	Placebo
Arm/Group Description	Participants will be given 1 fenofibrate (Tricor) 145mg and 4 fish oil placebos - supplies of study drug will be provided to last 8 weeks. Fenofibrate (Tricor)tablets: One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks	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. 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
Measure Participants	20	16
TNF-α at randomization	1.2 (0.5)	1.5 (1.2)
TNF-α 6-8 weeks post randomization	1.1 (0.4)	0.2 (1.1)

Adverse Events

Arm/Group Title	Tricor (145 mg/Day)		Placebo		Lovaza (900 mg/Day)		Lovaza (3,600 mg/Day)
Arm/Group Description	Participants will be given 1 Tricor 145mg and 4 fish oil placebos - supplies of study drug will be provided to last 8 weeks. Fenofibrate tablets: One 145 mg tablet taken once daily, in the evening, with food, for 6 to 8 weeks		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. 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		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. 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.		Participants will be given 4 Lovaza capsules and 1 Fenofibrate placebo - supplies of study drug will be provided to last 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.
All Cause Mortality
	Tricor (145 mg/Day)		Placebo		Lovaza (900 mg/Day)		Lovaza (3,600 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tricor (145 mg/Day)		Placebo		Lovaza (900 mg/Day)		Lovaza (3,600 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)		0/28 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Tricor (145 mg/Day)		Placebo		Lovaza (900 mg/Day)		Lovaza (3,600 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)		3/23 (13%)		8/28 (28.6%)		8/25 (32%)
Blood and lymphatic system disorders
> 2g drop in Hgb from baseline	1/24 (4.2%)	1	1/23 (4.3%)	1	4/28 (14.3%)	4	1/25 (4%)	1
General disorders
cold/allergy symptoms	3/24 (12.5%)	3	2/23 (8.7%)	2	4/28 (14.3%)	4	7/25 (28%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.