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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Inflammatory Responses	Drug: 4 g prescription omega-3 concentrate; Drug: Placebo	Not Applicable

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.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	21 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Basic Science
Official Title:	Effects of a Prescription Omega-3 Fatty Acid Concentrate in a Placebo-controlled Trial of Human Endotoxemia
Study Start Date :	May 2014
Actual Primary Completion Date :	April 2015
Actual Study Completion Date :	April 2015

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Placebo Comparator: Placebo; Identical olive oil capsules	Drug: Placebo; olive oil; Other Name: No other name (control)
Experimental: Omega-3; 4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks)	Drug: 4 g prescription omega-3 concentrate; 4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks; Other Names: Lovaza; Omacor

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change in C Reactive Protein (CRP) [ Time Frame: 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 :

1. Tumor Necrosis Factor-α (TNF-α) [ Time Frame: 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
2. Interleukin-6 (IL-6) [ Time Frame: 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

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	20 Years to 45 Years (Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

The specific exclusion criteria are:

1. Previous history of vasovagal reactions or unprovoked fainting (I.e. fainting as a result of prolonged standing, exercise)
2. Resting heart rate < 55 bpm
3. History of atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
4. History of diabetes mellitus (and/or a fasting glucose >126 mg/dL at screening)
5. 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
6. Self-reported history of allergy to fish
7. History of a non-skin malignancy within the previous 5 years
8. Renal insufficiency as defined by creatinine outside of lab defined normal range at Screening Visit
9. History of liver disease or abnormal LFTs (AST, ALT, Alk. Phos., GGT > 1.5x ULN; bilirubin > 2x ULN) at Screening Visit
10. Total white blood cell count less than or equal to 3.0 THO/uL
11. Hemoglobin less than 11.0 g/dL
12. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection
13. Self-reported history of HIV positive
14. Participants who have undergone any organ transplant
15. Individuals who currently use tobacco products or have done so in the previous 30 days.
16. Participants who are unwilling to discontinue use of nutritional supplements, herbs or vitamins unless approved by study staff.
17. 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
18. Elevated blood pressure (BP > 159/99) or use of any anti-hypertensive medications.
19. Latex allergy
20. Unwillingness to refrain from blood donation for 2 months prior to and following endotoxin administration
21. Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator
22. Inability to take study capsules
23. History of severe, repeated headaches
24. History of migraine
25. Medical condition that causes severe nausea or vomiting
26. Low resting blood pressure (SBP < 90 mmHg)
27. History of atrial fibrillation/flutter
28. Abnormal coagulation parameters (platelet count, prothrombin time with INR), documented coagulation abnormality, or use of anticoagulant medication
29. High LDL-C (> or = 160 mg/dL)

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Pennsylvania
Penn State University
University Park, Pennsylvania, United States, 16802

Sponsors and Collaborators

Penn State University

Pronova BioPharma

Investigators

Principal Investigator:	Gordon Jensen, MD, PhD	Penn State University

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Penny Kris-Etherton, Distinguished Professor of Nutrition, Penn State University
ClinicalTrials.gov Identifier:	NCT01813110 History of Changes
Other Study ID Numbers:	PRONOVA
First Posted:	March 18, 2013
Results First Posted:	August 1, 2017
Last Update Posted:	January 23, 2018
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Penny Kris-Etherton, Penn State University:

inflammation; omega-3; fish oil