Clinical trial NCT04152291: The Effect of E-EPA on Circulating LDL and Plasma Lipid Metabolism
Official title: The Effect of Ethyl Eicosapentaenoic Acid on Circulating Low-density Lipoproteins and Plasma Lipid Metabolism in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atherosclerosis
Low-density Lipoproteins Aggregation Susceptibility
Low-density Lipoprotein Lipid Composition
Cardiovascular Diseases
Keywords: Atherosclerosis
E-EPA
LDL aggregation susceptibility
Lipidomics
Resolvins
PON-1
LCAT
PLTP
CETP
Proteglycan binding
Lead sponsor: Wihuri Research Institute
Sponsor class: OTHER
Collaborators: name: University of Helsinki
name: Karolinska Institutet
name: Minerva Foundation Institute for Medical Research
First posted: 2019-11-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Baseline measurements are compared to different time points during the study.
Primary purpose: BASIC_SCIENCE

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, 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.

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

Primary outcomes:
measure: LDL Aggregation susceptibility
timeFrame: 30 days
measure: Lowering total triglycerides
timeFrame: 30 days
measure: EPA incorporation into LDL
timeFrame: 30 days
Secondary outcomes:
measure: Increases in EPA mediated resolvins
timeFrame: 30 days
measure: Changes in lipid metabolizing enzymes
timeFrame: 30 days
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Wihuri Research Institute
Study officials:
affiliation: Wihuri Research Institute
name: Katariina Öörni, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.