Clinical trial NCT05901246: Anti-eryptotic Effect of a Food Supplement with Plants Sterols in Hypercholesterolemia Treated with Statins
Official title: Anti-eryptotic Effect of Regular Intake of a Food Supplement with Plants Sterols in Subjects with Hypercholesterolemia Treated with Statins
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Hypercholesterolemia
Atherosclerosis
Keywords: Cholesterol
Plant Sterols
Eryptosis
Cholesterol oxidation products
Lead sponsor: University of Valencia
Sponsor class: OTHER
Collaborators: name: Hospital Clínico Universitario de Valencia
name: University of Bologna
First posted: 2023-06-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Potential anti-eryptotic effect of a regular intake of a plant sterol (PS)-containing food supplement, in moderate hypercholesterolemic patients treated with the PS-containing food supplement or placebo supplement.

Detailed description: Oxidative damage has been related to the externalization of phosphatidylserine in erythrocytes, an event associated with eryptosis (programmed death of erythrocytes). In addition, an increase in eryptosis has been observed in patients with hypercholesterolaemia. PS-enriched food supplements could be a nutritional strategy to improve risk factors in patients with moderate hypercholesterolemia treated with statins, constituting a synergistic treatment with these drugs. The present study aims to evaluate the eryptotic process (externalization of phosphatidylserine) after regular intake of a food supplement containing PS (2g/day) in patients with moderate hypercholesterolemia treated with statins. This is a case-control study with 32 cases (intake or a PS-containing food supplement) and 16 controls (placebo intake based on the excipient), with an intervention period of 6 weeks. The evaluation of eryptosis is carried out by determining the externalization of phosphatidylserine, the size of the erythrocytes and an ex vivo assay of adhesion of eryptotic erythrocytes to the vascular endothelium. In addition, the redox state (GSH), the in vivo oxidation of cholesterol (COPs), and biochemical and hematological parameters are evaluated. All parameters are evaluated at the beginning (week 0) and at the end of the intervention period (week 6).

Eligibility criteria: Inclusion Criteria:

* Participants with hypercholesterolemia (LDL cholesterol ≥ 160mg/dl at the time of diagnosis), receiving treatment with moderate intensity statins (atorvastatin 10-20 mg or simvastatin 20-40 mg or rosuvastatin 5-10 mg)
* No previous episodes of cardiovascular disease
* Absence of other analytical abnormalities or previous illnesses

Exclusion Criteria:

* Diabetes mellitus
* Participants in secondary prevention
* Treatment with lipid-lowering drugs other than atorvastatin, simvastatin or rosuvastatin
* Liver disease
* Renal failure
* Uncontrolled hypothyroidism
* Smokers
* Participants consuming foods enriched with PS or food supplements that contain PS

Primary outcomes:
measure: Changes in the externalization of phosphatidylserine
timeFrame: 0 and 6 weeks
measure: Changes in the adhesion to the endothelium by eryptotic erythrocytes
timeFrame: 0 and 6 weeks
Secondary outcomes:
measure: Changes in cell size ('forward scatter')
timeFrame: 0 and 6 weeks
measure: Changes in reduced glutathione cellular levels (GSH)
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic levels of cholesterol oxidation products (COPs)
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic glucose
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic total cholesterol
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic HDL-c
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic LDL-c
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic triglycerides
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic Apo A
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic Apo B
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic High-sensitivity C-reactive protein (hsCRP)
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic insulin
timeFrame: 0 and 6 weeks
measure: Changes in plasmatic Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: 0 and 6 weeks
measure: Evaluation of the mediterranean diet adherence to measure quality of life
timeFrame: 0 weeks
measure: Evaluation of the physical activity to measure quality of life
timeFrame: 0 weeks
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: University of Valencia
name: Amparo Asunción Alegría Torán, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cilla A, Lopez-Garcia G, Collado-Diaz V, Amparo Blanch-Ruiz M, Garcia-Llatas G, Barbera R, Martinez-Cuesta MA, Real JT, Alvarez A, Martinez-Hervas S. Hypercholesterolemic patients have higher eryptosis and erythrocyte adhesion to human endothelium independently of statin therapy. Int J Clin Pract. 2021 Nov;75(11):e14771. doi: 10.1111/ijcp.14771. Epub 2021 Sep 7.
citation: Restivo I, Attanzio A, Tesoriere L, Allegra M, Garcia-Llatas G, Cilla A. Anti-Eryptotic Activity of Food-Derived Phytochemicals and Natural Compounds. Int J Mol Sci. 2022 Mar 11;23(6):3019. doi: 10.3390/ijms23063019.