An interventional study of EPA + HT and EPA in Hypertriglyceridemia and Normal, sponsored by National Research Council, Spain. Active, not recruiting at 1 site in Spain. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-28.
Sponsored by National Research Council, Spain · Not applicable, Interventional, and Prevention
The primary aim of this study is to investigate the potential cardioprotective effects of daily nutritional doses of eicosapentaenoic acid (EPA) enriched with hydroxytyrosol (HT) on cardiovascular health, as well as its modulatory impact on the intestinal microbiota. This investigation will be conducted through a randomized, double-blind, crossover, and controlled nutritional intervention trial. The study population will include two cohorts: one with normotriglyceridemic individuals, and another with hypertriglyceridemic individuals. Participants will be randomly allocated to one of three intervention groups: (1) EPA+HT supplementation, (2) EPA alone, or (3) a placebo consisting of sunflower oil devoid of EPA.
The product to be tested is a combination of two key components: an oily preparation containing 97% eicosapentaenoic acid (EPA) and a natural extract (Oleacore®) with a high hydroxytyrosol content (10%). Oleacore® is naturally derived from olives using exclusively physical and mechanical methods and is commercialized by Olivenova Health SL (https://olivenova.com/es/). The EPA-97% component is supplied by Beeps Holding GMBH (https://bepsholding.com/el-holding/?lang=es). Three types of nutraceutical formulations will be prepared, and study participants will consume three capsules daily to achieve the following dosages:
The daily dose of 15 mg HT was selected based on the EFSA claim for the prevention of LDL oxidation , while the 2 g EPA dose was established following EFSA recommendations for triglyceride reduction.
A chronic, randomized, controlled, crossover, double-blind, free-living study design is proposed, spanning 46 weeks. Following a two-week washout period, during which the consumption of extra virgin olive oil, and olives will be restricted, participants will be grouped based on baseline characteristics (control or hypertriglyceridemia). They will then be randomized into three groups (randomization performed using SPSS software), such that one-third of participants will receive EPA+HT, another third will receive EPA without HT, and the remaining third will receive a placebo nutraceutical containing sunflower oil with no EPA or HT.
Each intervention phase will last 12 weeks. After completing one intervention, participants will undergo a four-week washout period before transitioning to the next intervention. Before the start of each phase, participants will be provided with all necessary capsules (EPA+HT, EPA, or placebo) along with detailed consumption guidelines.Volunteers will take the capsules with lunch and dinner.
Additionally, during the study, volunteers will consume a commercial olive oil with a minimal phenol content as their culinary oil. This olive oil will also be supplied by the research team for family use (1 L/2 weeks). Participants will be instructed to maintain their usual lifestyle throughout the study but will be restricted from consuming any other culinary oils apart from the one provided by the research group, as well as olives. Furthermore, the use of dietary supplements containing antioxidants, other than vitamins, will be prohibited.
Participants will attend the Human Nutrition Unit (UNH) at ICTAN-CSIC on six occasions, corresponding to the beginning and end of each intervention phase. Once eligibility has been confirmed based on the inclusion and exclusion criteria, participants will attend the UNH for signing the informed consent, receiving olive oil for household consumption, and receiving instructions to begin the study.
During visits V1-V6 (corresponding to the start and end of each intervention with the different nutraceuticals), participants will report to the UNH at ICTAN-CSIC. Upon arrival, they will provide a fasting urine sample from their first morning void and a stool sample collected within the previous 24 hours. Additionally, a trained nurse will collect a fasting blood sample (40 mL, distributed into tubes containing various anticoagulants).
Blood pressure and heart rate will also be measured. Furthermore, participants will undergo a comprehensive anthropometric and body composition assessment. Dietary habits and physical activity levels will be monitored and evaluated during these visits.
Compliance with the intervention will be monitored through monthly telephone follow-ups, the collection of unused capsules, and the measurement of specific biomarkers, including plasma phosphatidylcholine-EPA levels as a marker of omega-3 fatty acid intake and urinary HT metabolites.
324 studies on the registry are indexed under Hypertriglyceridemia; 38 are open to participants now.
This study's planned enrollment of 68 is close to the median of 66 across 288 interventional studies indexed under Hypertriglyceridemia.
Browse Hypertriglyceridemia studies →National Research Council, Spain is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
EPA + HT: intake of 2 g/d of EPA and 15 mg/d of HT (3 Type-1 capsules, EPA + HT)
Dietary Supplement: EPA + HT
EPA: intake of 2 g/d of EPA (3 Type-2 capsules, EPA)
Dietary Supplement: EPA
Sunflower Oil (SO): intake of 2 g/d of SO (3 Type-3 capsules, Placebo)
Dietary Supplement: Sunflower Oil
Drug page: Eicosapentaenoic Acid
Volunteers will consume during 12 weeks 2 g/d of EPA and 15 mg/d of HT, corresponding to 3 capsules. Additionally, they will consume a commercial olive oil with a minimal phenol content as their culinary oil that will be suplied by the research team for family use (1L/2 weeks)
Volunteers will consume during 12 weeks 2 g/d of EPA corresponding to 3 capsules. Additionally, they will consume a commercial olive oil with a minimal phenol content as their culinary oil that will be suplied by the research team for family use (1L/2 weeks)
Volunteers will consume during 12 weeks 2 g/d of Sunflower Oil, corresponding to 3 capsules. Additionally, they will consume a commercial olive oil with a minimal phenol content as their culinary oil that will be suplied by the research team for family use (1L/2 weeks)
Total cholesterol concentration
Total cholesterol in serum samples will be determined following reference methods recommended by the Sociedad Española de Bioquímica Clínica y Patología Molecular (SEQC) using the Roche Cobas Integra 400 plus analyser (Roche Diagnostics).
Time frame: 12 months
HDL-C, LDL-C, VLDL-C, and triglyceride concentrations
Measured in serum using reference or enzymatic methods recommended by SEQC.
Time frame: 12 months
Apolipoprotein A1 and B concentrations
Measured with clinical chemistry methods based on SEQC guidelines.
Time frame: 12 months
Aminotransferases: AST (ASAT) and ALT (ALAT) enzyme activity
Measured using enzymatic methods.
Time frame: 12 months
Uric acid, creatinine and glucose concentrations
Measured using standardised spectrophotometric methods.
Time frame: 12 months
Endothelial biomarkers
VCAM-1, ICAM-1, eNOS, E-selectin, and P-selectin concentrations will be measured in serum using ELISA.
Time frame: 12 months
Platelet function markers
Leukotriene B4 and prostaglandin E2 will be measured in serum using ELISAs (Cayman kits).
Time frame: 12 months
Serum cytokines (IL-6, IFN-γ, TNF-α, IL-10)
Serum concentrations of interleukin-6 (IL-6), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-10 (IL-10) will be determined using ELISA. These biomarkers reflect both pro- and anti-inflammatory responses.
Time frame: 12 months
C-Reactive Protein (CRP)
CRP will be measured using an automated ultrasensitive turbidimetric method (AU2700 Biochemistry analyser, Olympus).
Time frame: 12 months
Oxidized LDL and 8-hydroxy-2'-deoxyguanosine (8-OHdG)
LDLox and 8-OHdG will be measured in serum using ELISA.
Time frame: 12 months
Lipid peroxidation (TBARS)
TBARS will be measured as µM MDA equivalents using ELISA.
Time frame: 12 months
TAS will be assessed using a colorimetric assay or ELISA.
TAS will be assessed using a colorimetric assay or ELISA.
Time frame: 12 months
Total oxidative status (TOS)
TOS will be measured using ELISA.
Time frame: 12 months
Antioxidant enzyme activities (NOX, GSH, GPx, SOD)
NADPH oxidase (NOX), glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) will be measured using ELISA-based methods.
Time frame: 12 months
Systolic and Diastolic Blood Pressure
Systolic and diastolic blood pressure will be measured using an automatic arm sphygmomanometer (BS 150; Pic Indolor Diagnostic) at baseline and at the end of each intervention period. Measurements will be taken after the volunteer has rested on a chair for 5 minutes. Two consecutive readings will be taken on the left arm. If the values differ by more than 10-15 mmHg, a third reading will be recorded. The mean of the two (or three) closest readings will be used for analysis. Blood pressure will be expressed in mmHg..
Time frame: 12 months
Resting Heart Rate
Heart rate will be measured using the same automatic arm sphygmomanometer (BS 150; Pic Indolor Diagnostic) under the same conditions as blood pressure. Volunteers will rest for 5 minutes prior to the measurement. If multiple readings are required due to variation, the mean of the two (or three) closest values will be used. Heart rate will be expressed in beats per minute (bpm).
Time frame: 12 months
Fecal Short Chain Fatty Acids (SCFAs) Concentration
Short chain fatty acids (SCFAs) determination in faeces.The analytes will be analysed by gas chromatography system (Agilent Technologies Palo Alto, CA, USA) equipped with a mass spectrometer (MS) detector and Agilent DB-WAXtr column (100% polyethilen glycol, 60 m, 0.325 mm, 0250 um).
Time frame: 12 months
Fecal Lactate Concentration
Lactate levels in fecal samples will be measured using an Advanced Compact Ion Chromatographic instrument IC867 (Metrohm AG, Herisau, Switzerland).
Time frame: 12 months
Gut Microbiota Composition (16S rRNA Gene Profiling)
Microbial composition of fecal samples will be assessed by 16S rRNA gene amplicon sequencing. Genomic DNA will be extracted using the Quick-DNA™ Fecal/Soil Microbe Miniprep Kit (Zymo Research). Library preparation and sequencing will be conducted at Maastricht University (the Netherlands). Data analysis will be performed using the QIIME software package (v1.9.0), with taxonomic assignment based on the Greengenes database (v13.8).
Time frame: 12 months
Fasting glucose
Measured using SEQC-recommended methods.
Time frame: 12 months
Fasting insulin and C-peptide
Measured using immunoassays or ELISA.
Time frame: 12 months
Glycated hemoglobin (HbA1c)
Measured using HPLC or immunoturbidimetric methods.
Time frame: 12 months
Incretins (Glucagon and GLP-1)
Glucagon and GLP-1 concentrations will be measured using ELISA.
Time frame: 12 months
Adipokines (Leptin and PAI-1)
Leptin and plasminogen activator inhibitor-1 (PAI-1) will be measured using ELISA.
Time frame: 12 months
Started Feb 2025 (actual). Primary completion is estimated for Dec 2025, 10 months after the start.
Of 42 non-industry interventional studies with no phase under Hypertriglyceridemia, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 39. This study's planned 10 months is below that.
Counting every sponsor, half of 45 studies reached it within 23 months; a quarter within 7 and three quarters within 33.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Eicosapentaenoic Acid
National Research Council, Spain