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

NCT04152291 | Completed Results

• 1 other identifier: E-EPA
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Atherosclerosis; E-EPA; LDL aggregation susceptibility; Lipidomics; Proteoglycan binding; Icosapent ethyl; Fatty acid; Metabolism; Omega-3

Outcome Measures

Primary Outcomes (3)

• LDL Aggregation Susceptibility

  LDL aggregation susceptibility was induced in vitro by sphingomyelinase and measured using dynamic light scattering. Time-size curves were generated, and the inflection point (EC50)-the midpoint of the most rapid aggregation-was determined by nonlinear regression with a modified Hill equation. A longer time to reach EC50 indicates lower aggregation susceptibility, and thus a lower risk of future cardiovascular events.

  28 days

• Total Blood Triglycerides

  Percentage change in blood triglycerides after IPE-supplementation (day 28) compared to the baseline (day 0). Percentage change was calculated as follows: \[(day 28 - day 0) / day 0\] x 100.

  28 days

• EPA Incorporation Into LDL

  Total concentration of eicosapentaenoic acid in LDL lipoprotein fraction at baseline (day 0), and after IPE-supplementation (day 28).

  28 days

Other Outcomes (2)

• Lipoprotein Retention

  28 days

• Coronary Event Risk Test 2

  28 days

Study Arms (1)

E-EPA-diet group

EXPERIMENTAL

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.

Dietary Supplement: Ethyl-Eicosapentaenoic Acid (E-EPA)

Interventions

Ethyl-Eicosapentaenoic Acid (E-EPA) DIETARY_SUPPLEMENT

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

Also known as: E-EPA, Icosapent ethyl

E-EPA-diet group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy normolipidemic

You may not qualify if:

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

Sponsors & Collaborators

• Wihuri Research Institute: lead
• University of Helsinki: collaborator

Study Sites (1)

Wihuri Research Institute

Helsinki, Finland

Location

Related Publications (3)

• 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.

  PMID: 29982602 BACKGROUND

• 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.

  PMID: 30415628 BACKGROUND

• 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

  RESULT

Related Links

• Preprint of the research article from the study

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Limitations and Caveats

Covid-19 halted the study. This study's small sample size and focus on normolipidemic, Finnish, white Caucasian volunteers may limit its generalization to broader populations. The IPE preparation contained vitamin D3, which can influence plasma lipoprotein profiles, although it's kinetics differ from most measured parameters. The study's short duration also prevents assessment of IPE's long-term effects on lipoprotein profiles and cardiovascular outcomes.

Results Point of Contact

• Title: Professor Katariina Öörni
• Organization: Wihuri Research Institute

kati.oorni@wri.fi

+358 40 7023711

Study Officials

• Katariina Öörni, Professor, Ph.D

  Wihuri Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Group leader, Professor, Ph. D

Model Details: Baseline measurements are compared to different time points during the study.

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: November 12, 2019
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: September 22, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)