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| Name | Class |
|---|---|
| University of Helsinki | OTHER |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ethyl-Eicosapentaenoic Acid (E-EPA) | Dietary Supplement | 3,9 grams of E-EPA (Icosapent ethyl) is added to participants' normal diet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| Lipoprotein Retention | The binding of lipoproteins to aortic proteoglycans, measured ex vivo. At the end of the assay lipoprotein-associated bound cholesterol is measured in each well and compared to control wells to determine the binding probability of LDL particles to aortic proteoglycans. | 28 days |
| Coronary Event Risk Test 2 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Katariina Öörni, Professor, Ph.D | Wihuri Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wihuri Research Institute | Helsinki | Finland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29982602 | Background | 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. | |
| 30415628 |
| Label | URL |
|---|---|
| Preprint of the research article from the study | View source |
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Individual participant data will not be shared in compliance with EU's General Data Protection Regulation (GDPR)
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Recruitment took place in autumn/winter of 2019/2020 via in-house emailing lists. Participant suitability was assessed prior to the beginning of the supplementation. Healthy normolipidemic individuals aged 18-65 were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | IPE-supplementation Group | All the study participants will receive the same treatment. 3.9g of IPE (Ethyl-EPA) in capsules, which also include 75µg of D3-vitamin, daily for 28 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
Final number included in the analyses
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| ID | Title | Description |
|---|---|---|
| BG000 | IPE-supplementation Group | All the study participants will receive the same treatment. 3.9g of IPE (Ethyl-EPA) in capsules, which also include 75µg of D3-vitamin, daily for 28 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | Minutes | 28 days |
|
From enrollment until the end of the washout period (35 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IPE-supplementation Group | All the study participants will receive the same treatment. 3.9g of IPE (Ethyl-EPA) in capsules, which include 75µg of D3-vitamin, daily for 28 days. |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Katariina Öörni | Wihuri Research Institute | +358 40 7023711 | kati.oorni@wri.fi |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jun 17, 2025 | Jun 17, 2025 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C035276 | eicosapentaenoic acid ethyl ester |
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Baseline measurements are compared to different time points during the study.
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A clinical risk rest used to assess 10-year Coronary event risk. Based on plasma ceramides and phospholipids. Lower risk score indicates smaller future risk of coronary events. The four risk categories are: 0-3 (Low risk), 4-6 (Moderate risk), 7-8 (High risk), and 9-12 (Very high risk). |
| 28 days |
| 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. |
| Result | 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 |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
| LDL-cholesterol | Mean | Standard Deviation | mmol/L |
|
| Blood triglycerides | Mean | Standard Deviation | mmol/L |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
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| Primary | 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. | Posted | Mean | Standard Deviation | percentage of baseline triglycerides | 28 days |
|
|
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| Primary | EPA Incorporation Into LDL | Total concentration of eicosapentaenoic acid in LDL lipoprotein fraction at baseline (day 0), and after IPE-supplementation (day 28). | Posted | Mean | Standard Deviation | mmol/L | 28 days |
|
|
|
| Other Pre-specified | Lipoprotein Retention | The binding of lipoproteins to aortic proteoglycans, measured ex vivo. At the end of the assay lipoprotein-associated bound cholesterol is measured in each well and compared to control wells to determine the binding probability of LDL particles to aortic proteoglycans. | Posted | Mean | Standard Deviation | Bound cholesterol nmol/well | 28 days |
|
|
|
| Other Pre-specified | Coronary Event Risk Test 2 | A clinical risk rest used to assess 10-year Coronary event risk. Based on plasma ceramides and phospholipids. Lower risk score indicates smaller future risk of coronary events. The four risk categories are: 0-3 (Low risk), 4-6 (Moderate risk), 7-8 (High risk), and 9-12 (Very high risk). | Posted | Mean | Standard Deviation | Scores on a scale | 28 days |
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| 0 |
| 38 |
| 0 |
| 38 |
| 0 |
| 38 |
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