Clinical trial NCT06992323: Cardiometabolic Properties of Omega-3 Functionalized With Hydroxytyrosol
Official title: Cardiometabolic Properties of Omega-3 Funcionalized With Hydroxytyrosol in Healthy and Cardiovascular Risk Population
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypertriglyceridemia
Normal
Keywords: cardiovascular risk
omega 3
hydroxytyrosol
hypertriglyceridemia
Lead sponsor: National Research Council, Spain
Sponsor class: OTHER_GOV
Collaborators: name: Beps Holding GmbH
name: Olivenova Health Sl
First posted: 2025-05-28
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Chronic, randomized, controlled, cross-over, double-blind, and free-living study
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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:

1. 2 g of EPA + 15 mg of hydroxytyrosol (HT) (3 Type-1 capsules, EPA+HT),
2. 2 g of EPA (3 Type-2 capsules, EPA), and
3. 2 g of seed oil (sunflower) as a placebo (3 Type-3 capsules, Placebo).

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.

Eligibility criteria: Inclusion Criteria:

* Age: 18 to 70 years old
* Hypertriglyceridemia (150-250 mg/dl) or normal levels of triglycerides levels (\<150 mg/dl)

Exclusion Criteria:

* Presence of chronic illnesses
* Currently undergoing pharmacological treatment
* Smoking
* Pregnancy
* Adherence to a vegetarian or vegan diet

Primary outcomes:
measure: Total cholesterol concentration
timeFrame: 12 months
measure: HDL-C, LDL-C, VLDL-C, and triglyceride concentrations
timeFrame: 12 months
measure: Apolipoprotein A1 and B concentrations
timeFrame: 12 months
measure: Aminotransferases: AST (ASAT) and ALT (ALAT) enzyme activity
timeFrame: 12 months
measure: Uric acid, creatinine and glucose concentrations
timeFrame: 12 months
measure: Endothelial biomarkers
timeFrame: 12 months
measure: Platelet function markers
timeFrame: 12 months
measure: Serum cytokines (IL-6, IFN-γ, TNF-α, IL-10)
timeFrame: 12 months
measure: C-Reactive Protein (CRP)
timeFrame: 12 months
measure: Oxidized LDL and 8-hydroxy-2'-deoxyguanosine (8-OHdG)
timeFrame: 12 months
measure: Lipid peroxidation (TBARS)
timeFrame: 12 months
measure: TAS will be assessed using a colorimetric assay or ELISA.
timeFrame: 12 months
measure: Total oxidative status (TOS)
timeFrame: 12 months
measure: Antioxidant enzyme activities (NOX, GSH, GPx, SOD)
timeFrame: 12 months
Secondary outcomes:
measure: Systolic and Diastolic Blood Pressure
timeFrame: 12 months
measure: Resting Heart Rate
timeFrame: 12 months
measure: Fecal Short Chain Fatty Acids (SCFAs) Concentration
timeFrame: 12 months
measure: Fecal Lactate Concentration
timeFrame: 12 months
measure: Gut Microbiota Composition (16S rRNA Gene Profiling)
timeFrame: 12 months
measure: Fasting glucose
timeFrame: 12 months
measure: Fasting insulin and C-peptide
timeFrame: 12 months
measure: Glycated hemoglobin (HbA1c)
timeFrame: 12 months
measure: Incretins (Glucagon and GLP-1)
timeFrame: 12 months
measure: Adipokines (Leptin and PAI-1)
timeFrame: 12 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Institute of Food Science, Food Technology and Nutrition (ICTAN), CSIC
Study officials:
affiliation: National Research Council (CSIC)
name: Raquel Mateos Briz Tenured Scientist
role: PRINCIPAL_INVESTIGATOR
References: