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

NCT ID: NCT04152291

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-12
• Study Completion Date: 2024-12-31

Brief Summary

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.

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, triglycerides, 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.

Update at study conclusion 17.6.2025. Covid-19 halted our study progression leading to a partial cohort (final n=38). Covid-19 restrictions also prevented us from measuring plasma lipid metabolism enzymes and lipid mediated resolvins. As a results we expanded the lipoprotein lipidomics analysis to consist all three lipoprotein fractions (VLDL, LDL, and HDL) using LC/MS. Finally a clinical cardiovascular risk score assessment was also performed (CERT2/Hertta-test).

Conditions

Atherosclerosis; Low-density Lipoproteins Aggregation Susceptibility; Low-density Lipoprotein Lipid Composition; Cardiovascular Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

E-EPA-diet group

All the study participants will receive the same treatment. 3.9g of E-EPA in capsules, which also include 75µg of D3-vitamin, daily for 28 days.

Group Type: EXPERIMENTAL

Ethyl-Eicosapentaenoic Acid (E-EPA)

Intervention Type: DIETARY_SUPPLEMENT

3,9 grams of E-EPA (Icosapent ethyl) is added to participants' normal diet.

Interventions

Ethyl-Eicosapentaenoic Acid (E-EPA)

3,9 grams of E-EPA (Icosapent ethyl) is added to participants' normal diet.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

E-EPA; Icosapent ethyl

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Helsinki

OTHER

Sponsor Role: collaborator

Wihuri Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Katariina Öörni

Group leader, Professor, Ph. D

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katariina Öörni, Professor, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Wihuri Research Institute

Locations

Wihuri Research Institute

Helsinki, , Finland

Countries

Finland

References

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.

Reference Type: BACKGROUND

PMID: 29982602 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30415628 (View on PubMed)

Preprint/ Lauri Äikäs, Petri T. Kovanen, Martina Lorey, Reijo Laaksonen, Minna Holopainen, Hanna Ruhanen, Reijo Käkelä, Matti Jauhiainen, Martin Hermansson, Katariina Öörni. Remodelling of plasma lipoproteins by icosapent ethyl -supplementation and its impact on cardiovascular disease risk markers in normolipidemic individuals. MedRxiv 2024.11.27.24318042; doi: https://doi.org/10.1101/2024.11.27.24318042

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

https://www.medrxiv.org/content/10.1101/2024.11.27.24318042v1

Preprint of the research article from the study

Other Identifiers

E-EPA

Identifier Type: -

Identifier Source: org_study_id