Anti-eryptotic Effect of a Food Supplement With Plants Sterols in Hypercholesterolemia Treated With Statins

Sponsor

University of Valencia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05901246

Collaborator

Hospital Clínico Universitario de Valencia (Other), University of Bologna (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Hypercholesterolemia Atherosclerosis	Dietary Supplement: PS-containing dietary supplement Other: Placebo	N/A

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Basic Science

Official Title:

Anti-eryptotic Effect of Regular Intake of a Food Supplement With Plants Sterols in Subjects With Hypercholesterolemia Treated With Statins

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PS-containing dietary supplement Sachet containing a powdered ingredient source of microencapsulated free plant sterols (2,25 g ingredient/day)	Dietary Supplement: PS-containing dietary supplement Sachet containing a powdered ingredient source of microencapsulated free plant sterols (2,25 g ingredient/day)
Placebo Comparator: Placebo Sachet containing the excipients of the ingredient (2,25 g placebo/day)	Other: Placebo Sachet containing the excipients of the ingredient (2,25 g placebo/day)

Arm

Intervention/Treatment

Experimental: PS-containing dietary supplement

Sachet containing a powdered ingredient source of microencapsulated free plant sterols (2,25 g ingredient/day)

Dietary Supplement: PS-containing dietary supplement

Sachet containing a powdered ingredient source of microencapsulated free plant sterols (2,25 g ingredient/day)

Placebo Comparator: Placebo

Sachet containing the excipients of the ingredient (2,25 g placebo/day)

Other: Placebo

Sachet containing the excipients of the ingredient (2,25 g placebo/day)

Outcome Measures

Primary Outcome Measures

Changes in the externalization of phosphatidylserine [0 and 6 weeks]
The externalization of phosphatidylserine, assessed by flow cytometry (Kit Annexin V) with repeated measures (at the beginning and at the end of the intervention)
Changes in the adhesion to the endothelium by eryptotic erythrocytes [0 and 6 weeks]
The adhesion to the endothelium by eryptotic erythrocytes, assessed with parallel-plate flow chamber technique in human umbilical vein endothelial cells (HUVECs) with repeated measures (at the beginning and at the end of the intervention)

Secondary Outcome Measures

Changes in cell size ('forward scatter') [0 and 6 weeks]
Cell size, assessed by flow cytometry with repeated measures (at the beginning and at the end of the intervention)
Changes in reduced glutathione cellular levels (GSH) [0 and 6 weeks]
GSH, assessed by flow cytometry (Green CMFDA), with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic levels of cholesterol oxidation products (COPs) [0 and 6 weeks]
COPs levels, assessed by gas chromatography-mass spectometry, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic glucose [0 and 6 weeks]
Glucose, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic total cholesterol [0 and 6 weeks]
Total cholesterol, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic HDL-c [0 and 6 weeks]
HDL-c, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic LDL-c [0 and 6 weeks]
LDL-c, calculated by the Friedewald's formula, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic triglycerides [0 and 6 weeks]
Triglycerides, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic Apo A [0 and 6 weeks]
Apo A, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic Apo B [0 and 6 weeks]
Apo B, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic High-sensitivity C-reactive protein (hsCRP) [0 and 6 weeks]
hs CRP, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic insulin [0 and 6 weeks]
Insulin, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Changes in plasmatic Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [0 and 6 weeks]
HOMA-IR, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of the intervention)
Evaluation of the mediterranean diet adherence to measure quality of life [0 weeks]
Mediterranean diet adherence screener (MEDAS) is used, consisting in 14 questions (each one 0 or 1 point, final score between 0 and 14). Results are ranged between 0-7 points (low adherence), 7-10 (moderate adherence), and 10-14 (high adherence). This is only evaluated at the beginning of the intervention.
Evaluation of the physical activity to measure quality of life [0 weeks]
International physical activity questionaire-short form (IPAC-SF) is used, consisting in 7 questions. Intensity, frequency and duration of the exercise are evaluated through metabolic equivalent of task (METs). This allows to differentiate 3 levels of physical activity: Low: Not enough activity to achieve the next level Moderate: 3 or more days of vigorous physical activity for at least 20 minutes per day, 5 or more days of moderate physical activity and/or walking at least 30 minutes per day, or 5 or more days of any combination of walking, moderate or vigorous physical activity achieving at least a total of 600 METs High: Vigorous physical activity at least 3 days per week achieving a total of at least 1500 METs, or 7 days of any combination of walking, with moderate and/or vigorous physical activity, achieving a total of at least 3000 METs This is only evaluated at the beginning of the intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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