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AtherosclerosisEPA&LDLNCT04152291

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

A study testing Ethyl-Eicosapentaenoic Acid (E-EPA) in people with Atherosclerosis and Low-density Lipoproteins Aggregation Susceptibility, run by Wihuri Research Institute at 1 site in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
What is being tested?
Ethyl-Eicosapentaenoic Acid (E-EPA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
1 siteFinland
Study dates
12 Nov 2019to 31 Dec 2024
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Healthy normolipidemic

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Finland1 site

  • Wihuri Research Institute

    Helsinki

Other trials in Finland

About this study

Official title: 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.

Read the 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).

Being tested
Ethyl-Eicosapentaenoic Acid (E-EPA)
Keywords
Atherosclerosis, E-EPA, LDL aggregation susceptibility, Lipidomics, Proteoglycan binding, Icosapent ethyl, Fatty acid, Metabolism, Omega-3
Medical subject headings
Atherosclerosis, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ethyl-Eicosapentaenoic Acid (E-EPA)Dietary supplement

    Also called E-EPA, Icosapent ethyl

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

Study groups in NCT04152291
Study groupRoleWhat they receive
E-EPA-diet groupExperimentalAll 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.
Receives: Dietary Supplement: Ethyl-Eicosapentaenoic Acid (E-EPA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

  2. 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.

    Measured: 28 days

  3. EPA Incorporation Into LDL

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

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2019
  2. Study start12 Nov 2019
  3. Primary completion30 Jun 2024
  4. Study completion31 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
Baseline measurements are compared to different time points during the study.
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04152291
Sponsor's protocol ID
E-EPA
Acronym
EPA&LDL
Status last verified
Sep 2025
First submitted
1 Nov 2019
Last updated
22 Sep 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data will not be shared in compliance with EU's General Data Protection Regulation (GDPR)

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.

    PubMed 29982602

  • 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.

    PubMed 30415628

  • 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

  • Aikas L, Kovanen PT, Lorey MB, Laaksonen R, Holopainen M, Ruhanen H, Kakela R, Jauhiainen M, Hermansson M, Oorni K. Icosapent ethyl-induced lipoprotein remodeling and its impact on cardiovascular disease risk markers in normolipidemic individuals. JCI Insight. 2025 Oct 8;10(19):e193637. doi: 10.1172/jci.insight.193637. eCollection 2025 Oct 8.

    PubMed 41059572

Questions about this trial

What is this clinical trial studying?

A study testing Ethyl-Eicosapentaenoic Acid (E-EPA) in people with Atherosclerosis and Low-density Lipoproteins Aggregation Susceptibility, run by Wihuri Research Institute at 1 site in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

LDL Aggregation Susceptibility (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04152291, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025.

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