The Effect of E-EPA on Circulating LDL and Plasma Lipid Metabolism (EPA&LDL)

The Effect of Ethyl Eicosapentaenoic Acid on Circulating Low-density Lipoproteins and Plasma Lipid Metabolism in Healthy Volunteers

40-70 healthy volunteers of ages 18 to 65 participate in a E-EPA-diet where 3,9 grams of E-EPA is added to their normal diet and lifestyles for a month. Blood samples will be collected before the study and at weeks 1 and 4 and also, two weeks after finishing the diet. Main study focuses are LDL aggregation susceptibility, lipid composition and proteoglycan binding affinity. In addition, important plasma lipid metabolism enzymes and lipid mediated resolvins are measured as well as several baseline characteristics.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Atherosclerosis; Low-density Lipoproteins Aggregation Susceptibility; Low-density Lipoprotein Lipid Composition
• Intervention / Treatment: Dietary supplement: Ethyl-Eicosapentaenoic Acid (E-EPA)

Detailed Description

Four grams of daily E-EPA was found to significantly decrease atherosclerotic cardiovascular diseases in the REDUCE-IT study. In the upcoming study the effect of E-EPA to low-density lipoprotein (LDL) aggregation susceptibility is measured using dynamic light scattering technique to continuously measure particles size while inducing aggregation. LDL Lipid composition is analyzed using electrospray mass spectrometer optimized for lipid measurements. Previously is reported that the aggregation susceptibility is affected by the lipid composition which is modifiable (Ruuth et. al. Eur.H.Journal 2018). Common disease factors such as total cholesterol, LDL, HDL, triglyserides, ApoB-100, ApoA-I, Lp(a) and different modified LDL levels are measured. Also, activities of lipid metabolism enzymes like PON-1, LCAT, CETP, PLTP and lipid mediated resolvins are looked into. Objective is to identify changes and possible pathways that are altered by the increase of E-EPA and to use the data to possibly explain the health benefits of EPA.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Wihuri Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy normolipidemic

Exclusion Criteria:

• Prescription of blood thinner medicine
• Circulating Low-density lipoprotein > 5mmol/l, Triglycerides >3mmol/l
• Chronic use of pain medication
• Fish allergy
• Pregnancy
• Breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E-EPA-diet group; All the study participants will receive the same treatment. 3.9g of E-EPA in capsules, which include 75µg of D3-vitamin, daily for 30 days.	Dietary supplement: Ethyl-Eicosapentaenoic Acid (E-EPA); 3,9 grams of EPA is added to participants' normal diet.; Other Names: E-EPA; Icosapentaenoic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL Aggregation susceptibility	Lowering in LDL aggregation susceptibility	30 days
Lowering total triglycerides	Lowering of total circulating triglycerides	30 days
EPA incorporation into LDL	Incorporation of EPA into circulating LDL lipid composition	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increases in EPA mediated resolvins	Increases in circulating resolvins, derived from EPA	30 days
Changes in lipid metabolizing enzymes	Changes in activities of circulating lipid metabolizing enzymes such as PON-1, LCAT, PLTP and CETP	30 days

Collaborators and Investigators

• Sponsor: Wihuri Research Institute
• Collaborators: Karolinska Institutet; University of Helsinki; Minerva Foundation Institute for Medical Research
• Investigators: Principal Investigator: Katariina Öörni, Ph.D, Wihuri Research Institute

Publications and helpful links

General Publications

• Ruuth M, Nguyen SD, Vihervaara T, Hilvo M, Laajala TD, Kondadi PK, Gistera A, Lahteenmaki H, Kittila T, Huusko J, Uusitupa M, Schwab U, Savolainen MJ, Sinisalo J, Lokki ML, Nieminen MS, Jula A, Perola M, Yla-Herttula S, Rudel L, Oorni A, Baumann M, Baruch A, Laaksonen R, Ketelhuth DFJ, Aittokallio T, Jauhiainen M, Kakela R, Boren J, Williams KJ, Kovanen PT, Oorni K. Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths. Eur Heart J. 2018 Jul 14;39(27):2562-2573. doi: 10.1093/eurheartj/ehy319.
• Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Anticipated): May 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Atherosclerosis; Lipidomics; E-EPA; LDL aggregation susceptibility; Resolvins; PON-1; LCAT; PLTP; CETP; Proteglycan binding
• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Cardiovascular Diseases; Disease Susceptibility; Atherosclerosis; Platelet Aggregation Inhibitors; Lipid Regulating Agents; Eicosapentaenoic acid ethyl ester
• Other Study ID Numbers: E-EPA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No