Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation

This study has been completed.
Sponsor:
Collaborator:
USDA Beltsville Human Nutrition Research Center
Information provided by (Responsible Party):
Penny Kris-Etherton, Penn State University
ClinicalTrials.gov Identifier:
NCT01078909
First received: March 1, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response to in vivo and ex vivo endotoxin challenge as measured by the production over time of several inflammatory markers.


Condition Intervention Phase
Cardiovascular Disease
Inflammation
Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • Change in Inflammatory Markers [ Time Frame: Baseline (before LPS administration), 1, 2, 3, 4, 6, 12, and 24 hrs post LPS administration; 2, 3 and 5 days post LPS administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Lipid Mediators [ Time Frame: 1, 2, 3 and 5 days post LPS administration ] [ Designated as safety issue: No ]

Enrollment: 116
Study Start Date: October 2011
Study Completion Date: April 2014
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 300mg Fish Oil (EPA + DHA) Supplement Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
Other Names:
  • Omega-3 Fatty Acids
  • Fish Oil
Experimental: 600mg Fish Oil (EPA+DHA) Supplement Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
Other Names:
  • Omega-3 Fatty Acids
  • Fish Oil
Experimental: 900mg Fish Oil (EPA + DHA) Supplement Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
Other Names:
  • Omega-3 Fatty Acids
  • Fish Oil
Experimental: 1800mg Fish Oil (EPA + DHA) Supplement Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
Other Names:
  • Omega-3 Fatty Acids
  • Fish Oil
Placebo Comparator: Placebo Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
Other Names:
  • Omega-3 Fatty Acids
  • Fish Oil

Detailed Description:

Inflammation is an important biological process initiated by the immune system in response to injury, irritation or infection. 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 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.

Some studies have demonstrated a dose-response relationship between dietary eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and increased membrane (phospholipid) EPA and DHA. Red blood cell (RBC) EPA + DHA content has been proposed as a potential, modifiable marker for coronary heart disease (CHD) risk. It is well established that these 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 nutritionally-relevant intakes of omega-3 fatty acids are able to blunt the usual response to an inflammatory stimulus. We propose to test this hypothesis using both in vivo (i.v. endotoxin challenge) and ex vivo (endotoxin-stimulated monocytes) models in a 6-month, dose-response study with marine-derived omega-3 fatty acid supplements in healthy volunteers.

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men and non-pregnant/lactating women between the ages of 20 and 45
  • BMI >19.9 and <30.0
  • Able to give written informed consent and willing to comply with all study- related procedures.

Exclusion Criteria:

  • Previous history of heart disease or diabetes
  • Renal Insufficiency
  • Chronic anti-inflammatory use
  • Systolic blood pressure < 90
  • Individuals currently using tobacco products or have done so in the previous 30 days
  • Individuals taking Omega-3 fatty acid supplements or their usual intake of fish is greater than 3-4 servings per month.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078909

Locations
United States, Pennsylvania
Penn State University
University Park, Pennsylvania, United States, 16802
Sponsors and Collaborators
Penn State University
USDA Beltsville Human Nutrition Research Center
Investigators
Principal Investigator: Gordon L Jensen, MD, PhD Penn State University
  More Information

No publications provided by Penn State University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Penny Kris-Etherton, Distinguished Professor of Nutrition, Penn State University
ClinicalTrials.gov Identifier: NCT01078909     History of Changes
Other Study ID Numbers: PKE LPS
Study First Received: March 1, 2010
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Penn State University:
Cardiovascular disease
Inflammation
Fish Oil
Omega-3 Fatty Acids
LPS
Endotoxin

Additional relevant MeSH terms:
Cardiovascular Diseases
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014