Clinical trial NCT04440202: Cardioprotective Properties of ELAIOTSIPOURA
Official title: Cardioprotective Properties of Sea Bream Bred With a Fraction of Polar Lipids Extracted From Olive Oil By-products: the ELAIOTSIPOURA Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiometabolic Health
Keywords: fish
sea bream
dietary intervention
olive oil
polar lipids
platelet aggregation
thrombosis
inflammation
cardioprotection
Lead sponsor: Harokopio University
Sponsor class: OTHER
Collaborators: name: Nireus Aquaculture
name: University of Thessaly
name: Cretan Herbalchem S.A.
name: National and Kapodistrian University of Athens
name: European Regional Development Fund (project code: T1EDK- 00687)
First posted: 2020-06-19
Enrollment: 34
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Several studies over the last decades have demonstrated the important role of nutrition for either the prevention of chronic diseases, such as cardiovascular disease and cancer, or the increase of their risk. One dietary component with several health benefits as supported by several epidemiological and clinical studies is fish consumption. Both the European Society of Cardiology and the American Heart Association recommend the consumption of at least two servings of fish per week for protection against cardiovascular disease. Nevertheless, the growth of the human population and the rising consumers' awareness, result in a constantly increasing demand for the supply of fish. Aquaculture is significantly contributing to fish supplies all over the world and over the past few years, important breakthroughs have occurred in the replacement of fish oil, traditionally used in aquacultures, by plant oils in compounded fish feeds as a mean to improve the nutritional value of the produced fish. Under this perspective, the utilization of olive oil by-products, widely available in the Mediterranean countries, in fish feeds could result in significant economic and environmental impact. Therefore, the aim of the present double-blind, randomized, crossover clinical trial is to explore the potential cardioprotective properties of "elaiotsipoura", a novel sea bream fed with bioactive lipids isolated from olive oil by-products, against conventionally fed sea bream, in apparently healthy volunteers.

Detailed description: Cardiovascular diseases (CVD) represent a major public health challenge and the leading cause of mortality worldwide. The elucidation of CVD pathogenesis, as well as the identification of efficient strategies for their prevention and treatment, have been the subject of intense research in recent years. The platelet activation factor (PAF) is one of the most important mediators of atherosclerosis, given that it is produced by cells involved in the formation of atherosclerotic plaque (e.g. endothelial cells, platelets, smooth muscle cells, macrophages and neutrophils) under conditions that predispose to CVD, i.e. inflammation, oxidative stress, endothelial dysfunction and dyslipidaemia. PAF acts on neighbouring cells by inducing a series of responses (e.g. chemotaxis, expression of adhesion molecules and accumulation of platelets) that eventually lead to endothelial and atherosclerotic damage.

The Mediterranean diet (MD) is a dietary pattern with well-established protective effects against the development of CVD. Several foods representative of the MD, such as honey, wine and fish, have been found to be rich in nutrients, mainly of lipid nature, that can act as PAF inhibitors. Investigators have recently focused on olive oil, from which a bioactive polar lipoid (BPL) fraction with strong PAF inhibitors was extracted. The most important of these inhibitors were structurally classified and found to belong to the class of glycolipids. This BPL fraction showed strong anti-atherogenic properties in hypercholesterolaemic rabbits, stronger than those produced by the same amount of olive oil. BPLs could therefore be a bioactive extract that could potentially be used as an additive in biofunctional foods or as a dietary supplement, aiming at preventing atherosclerosis and CVD. However, olive oil cannot be systematically used as the source of such an extract, since the large quantities of olive oil required to extract BPLs combined with its high price make olive oil an unsustainable raw material. In this context, olive oil by-products could be a more suitable alternative source, and their extract has been found to be rich in phenolic compounds and to exert a similar inhibitory effect against PAF. This alternative extract has already been tested in hypercholesterolaemic rabbits and was shown to significantly reduce the thickness of atherosclerotic lesions. In addition, it has already been used by "Nireus Aquaculture" for pilot fish farming.

The aim of the present study is to evaluate the potential cardio-protective properties of an innovative fish bred with bioactive lipids derived from olive oil by-products.

The study will be a randomized, cross-over, double blind clinical trial. The study sample will consist of 30 apparently healthy volunteers aged 35-70 years, with a body mass index of 25-35 kg/m2, who will not be under certain types of medication, namely antidiabetic, anxiolytics/ antidepressants and cortisol. Other prescribed medications and dietary supplements will be allowed, provided that their reception will remain stable by participants throughout the trial. Individuals with diabetes mellitus, active cancer, cardiovascular diseases, chronic inflammatory diseases or psychiatric diseases, as well as those on a weight-loss diet or with recent significant changes in their lifestyle habits will be excluded from the study. Participants will consume 2 servings per week of either a conventional sea bream fillet or an enriched with bioactive lipids derived from olive oil by-products sea bream fillet (serving size: 200 g cooked fish) for 4 weeks, with a 4-week wash-out period between the two interventions. The study physician will be on a weekly contact with each participant to systematically record potential side-effects and will be in charge of terminating the intervention if needed.

Participants will be assessed in terms of lifestyle habits (dietary and physical activity habits), and blood samples will be collected, both at the beginning and end of each intervention period (a total of 4 assessments). Dietary habits will be assessed through a validated for the Greek population food frequency questionnaire, while physical activity level will be assessed through the Athens Physical Activity Questionnaire, also validated in the Greek population. Adherence to dietary intervention will be assessed through weekly self-monitoring diaries, in which participants will record the exact day and quantity of fish they consumed. Participants' diastolic and systolic blood pressure will be measured by the study physician at the 4 assessments throughout the study. All blood samples will be collected and analyzed in the Laboratories of Clinical Nutrition and of Biology, Biochemistry, Physiology and Microbiology of the Department of Nutrition and Dietetics of Harokopio University of Athens by experienced personnel. The ability of the platelet-rich plasma (PRP) to be accumulated under the influence of PAF and adenosine diphosphate (ADP) will be assessed by calculating the corresponding efficiency concentration fifty (EC50) values. A priori statistical power analysis showed that 25 participants in each arm were required to achieve statistical power equal to 83% at 5% significance level of two-sided hypotheses that evaluated 1 standard deviation (SD) differences based on EC50 values of platelet aggregation induced by PAF. In addition, thrombosis markers, oxidation and inflammation markers, as well as glycemic and lipidemic profile parameters, will be measured in participants' blood and urine samples.

Eligibility criteria: Inclusion Criteria:

1. Age 35-70 years old
2. Body mass index 25-35 kg/m2
3. Habitual fish consumption ≤1 portion/week (1 portion: 150 g cooked fish)

Exclusion Criteria:

1. Presence of diabetes mellitus, active cancer, cardiovascular disease, chronic inflammatory or psychiatric diseases
2. Reception of antidiabetic, anxiolytic, antidepressant or cortisol medication
3. Habitual excessive alcohol intake (\>210 g of ethanol/week for men and \>140 g of ethanol/week for women)
4. Currently on a weight-loss diet or recent change (within 6 months) in lifestyle habits

Primary outcomes:
measure: Change from baseline of adenosine diphosphate-induced platelet aggregation at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
measure: Change from baseline of platelet activating factor-induced platelet aggregation at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
measure: Change from baseline in tissue plasminogen activator activity at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
measure: Change from baseline in of plasminogen activator inhibitor-1 activity at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
Secondary outcomes:
measure: Change from baseline in high sensitivity interleukin-6 levels at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
measure: Change from baseline in high sensitivity interleukin-10 levels at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
measure: Change from baseline in soluble P-selectin levels at 4 weeks
timeFrame: 0 (baseline) and 4 weeks
Other outcomes:
Locations:
city: Kallithéa
country: Greece
facility: Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University
state: Attica
Study officials:
affiliation: Department of Nutrition and Dietetics, Harokopio University
name: Smaragdi Antonopoulou, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Nutrition and Dietetics, Harokopio University
name: Tzortzis Nomikos, PhD
role: STUDY_CHAIR
affiliation: Department of Nutrition and Dietetics, Harokopio University
name: Elizabeth Fragopoulou, PhD
role: STUDY_CHAIR
affiliation: Department of Nutrition and Dietetics, Harokopio University
name: Meropi D Kontogianni, PhD
role: STUDY_CHAIR
affiliation: Department of Nutrition and Dietetics, Harokopio University
name: Michael Georgoulis, PhD
role: STUDY_CHAIR
References:
citation: Antonopoulou S, Fragopoulou E, Karantonis HC, Mitsou E, Sitara M, Rementzis J, Mourelatos A, Ginis A, Phenekos C. Effect of traditional Greek Mediterranean meals on platelet aggregation in normal subjects and in patients with type 2 diabetes mellitus. J Med Food. 2006 Fall;9(3):356-62. doi: 10.1089/jmf.2006.9.356.
citation: Karantonis HC, Fragopoulou E, Antonopoulou S, Rementzis J, Phenekos C, Demopoulos CA. Effect of fast-food Mediterranean-type diet on type 2 diabetics and healthy human subjects' platelet aggregation. Diabetes Res Clin Pract. 2006 Apr;72(1):33-41. doi: 10.1016/j.diabres.2005.09.003. Epub 2005 Oct 19.