Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation

Not Applicable

Completed

Conditions: Inflammatory Responses

Interventions: Drug: Placebo
Drug: 4 g prescription omega-3 concentrate

Registration Number: NCT01813110

Lead Sponsor: Penn State University

Brief Summary: The purpose of this study is to assess whether the marine omega-3 fatty acids can attenuate inflammatory responses to endotoxin challenge.

Detailed Description: Controlled endotoxin infusion has been used widely as a model system to evaluate anti-inflammatory mediators and therapies in a controlled, in vivo setting. It is well established that infusion of bacterial endotoxin (also known as lipopolysaccharide or LPS) in humans results in a marked increase in inflammatory cytokines, most notably TNF-α, IL-1, IL-6 and IL-8, CRP, granulocyte colony stimulating factor (GCSF); eicosanoids, such as prostaglandin (PG) E2 and other mediators. Administration of endotoxin, even at a low dose (0.6 ng/kg) elevates circulating concentrations of inflammatory cytokines, and mimics the inflammatory effects of chronic diseases. This model has been used for decades and has proved to be safe and informative for evaluating anti-inflammatory therapeutic interventions on human inflammation and downstream consequences.

Prolonged or chronic inflammation is involved in the etiology of several diseases such as cardiovascular disease (CVD), diabetes, rheumatoid arthritis, cancer, and neurodegenerative diseases such as Alzheimer's disease. The evidence base clearly demonstrates benefits of diet in ameliorating inflammation and reducing the burden of chronic disease. With respect to marine-derived omega-3 fatty acids and various markers of inflammation related to cardiovascular disease (CVD), both population studies and randomized controlled supplementation trials have yielded mixed results. It is well established that these omega-3 fatty acids are precursors of series-3 prostanoids, thromboxanes, 5-series leukotrienes, and novel lipid mediators such as resolvins and protectins that have anti-inflammatory effects. We hypothesize that supplementation of omega-3 fatty acids will blunt the response to an inflammatory stimulus and/or enhance the resolution phase.

We propose to test this hypothesis using an in vivo endotoxin challenge with a pharmacological dose of omega-3 fatty acid ethyl esters (P-OM3, 3.4 g/d EPA + DHA) in healthy volunteers. Our proposed approach is novel in that we will provoke an in vivo inflammatory response by infusing human subjects with a low dose (0.6 ng/kg body weight) of sterile endotoxin (lipopolysaccharide \[LPS\]) in contrast to studies that have attempted to reverse established inflammatory pathology. Results from our proposed research will advance our understanding of the effect of omega-3 fatty acids on prevention/attenuation of an inflammatory response.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 21

Inclusion Criteria

Men between the ages of 20 and 45.
BMI ≥20 and ≤30
Participants who are able to give written informed consent and willing to comply with all study-related procedures.
Any race or ethnic background is acceptable
Non-smoking

The specific exclusion criteria are:

Previous history of vasovagal reactions or unprovoked fainting (I.e. fainting as a result of prolonged standing, exercise)
Resting heart rate < 55 bpm
History of atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
History of diabetes mellitus (and/or a fasting glucose >126 mg/dL at screening)
Chronic anti-inflammatory medication use or treatment with aspirin, NSAIDs, COX-2 inhibitors; steroids or any immunomodulatory therapy 2 weeks prior to the screening visit
Self-reported history of allergy to fish
History of a non-skin malignancy within the previous 5 years
Renal insufficiency as defined by creatinine outside of lab defined normal range at Screening Visit
History of liver disease or abnormal LFTs (AST, ALT, Alk. Phos., GGT > 1.5x ULN; bilirubin > 2x ULN) at Screening Visit
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
Participants who have undergone any organ transplant
Individuals who currently use tobacco products or have done so in the previous 30 days.
Participants who are unwilling to discontinue use of nutritional supplements, herbs or vitamins unless approved by study staff.
Participants who are unwilling to eliminate omega-3 fatty acid (EPA + DHA) supplements and/or fortified food, or have a usual intake of high omega-3 fish (tuna and other non-fried fish) > 2 servings per week
Elevated blood pressure (BP > 159/99) or use of any anti-hypertensive medications.
Latex allergy
Unwillingness to refrain from blood donation for 2 months prior to and following endotoxin administration
Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator
Inability to take study capsules
History of severe, repeated headaches
History of migraine
Medical condition that causes severe nausea or vomiting
Low resting blood pressure (SBP < 90 mmHg)
History of atrial fibrillation/flutter
Abnormal coagulation parameters (platelet count, prothrombin time with INR), documented coagulation abnormality, or use of anticoagulant medication
High LDL-C (> or = 160 mg/dL)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Identical olive oil capsules
Omega-3	4 g prescription omega-3 concentrate	4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks)

Primary Outcome Measures

Name	Time	Method
Change in C Reactive Protein (CRP)	24 hours post endotoxin administration, following each 8 week intervention	Change in blood levels of CRP at 24 hours post endotoxin administration, after each 8 week intervention

Secondary Outcome Measures

Name	Time	Method
Tumor Necrosis Factor-α (TNF-α)	2 hours post endotoxin administration, following each 8 week intervention	Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention
Interleukin-6 (IL-6)	2 hours post endotoxin administration, following each 8 week intervention	Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention