Clinical trial NCT06481020: Plant Sterols on Cardiovascular Markers, Microbiota and Sterol Metabolism (Cardiofoodsterol)
Official title: Effect of Plant Sterols on Inflammatory, Endothelial Function and Oxidative Stress Markers, Microbiota and Sterol Metabolism in a Cardiovascular Risk Population
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiovascular Diseases
Hypercholesterolemia
Prediabetic State
Overweight and Obesity
Keywords: Cholesterol LDL
Plant Sterols
Inflammation
Oxidative Stress
Microbiota
Sterol Metabolites
Endothelial function
Bioimpedance
Dietary Intake
Physical Activity
Lead sponsor: University of Valencia
Sponsor class: OTHER
Collaborators: name: Hospital Universitario La Fe
name: University of Bologna
First posted: 2024-07-01
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Potential cholesterol-lowering effect of a regular intake of a plant sterol (PS)-containing food supplement, in overweight/obese type 1 or 2, normoglycemic/pre-diabetic, with LDL-cholesterol values \> 115 mg/dl and not pharmacologically treated participants treated with the PS-containing food supplement or placebo supplement.

Detailed description: Cardiovascular disease (CVD) is the leading cause of death worldwide, with hypercholesterolemia being one of the main risk factors for CVD. The deposition and oxidation of LDL-cholesterol particles triggers a series of molecular events favoring chronic low-grade inflammation, endothelial dysfunction and oxidative stress. This situation promotes atherogenesis thus increasing cardiovascular risk. Obesity favors the secretion of pro-inflammatory mediators and promotes the recruitment of macrophages to adipose tissue, insulin resistance, hyperglycemia and hyperlipidemia, thus increasing the risk of CVD. In addition, obesity has been associated with gut dysbiosis, which in turn is associated with atherosclerosis in some studies. Beneficial effects of PS on LDL-cholesterol and inflammatory, endothelial dysfunction and oxidative stress markers have been reported by several clinical trials. A meta-analysis suggests a lowering effect of PS on body mass index (BMI) in participants with BMI\>25. Furthermore, the consumption of PS has been beneficially associated in in vitro studies with changes in intestinal microbial profile, sterol metabolism and short chain fatty acids (SCFA) production. Therefore, the hypothesis is if the consumption of PS as a food supplementation could reduce cardiovascular risk. The present study aims to evaluate the LDL-cholesterol serum levels after regular intake of a food supplement containing PS (2 g/day) in overweight/obese type 1 or 2 patients, normoglycemic /pre-diabetic and with LDL-cholesterol values \> 115 mg/dl not pharmacologically treated. This is a crossover study with 21 participants (intake of a food supplement containing PS) and 21 participants (intake of excipient-based placebo), with a first intervention period of 8 weeks. After a 6-week washout period, the treatments are switched, with a second intervention period of 8 weeks. In addition, to the LDL-cholesterol lowering assessment, other biochemical, hematological, inflammatory, endothelial dysfunction and oxidative stress parameters are assessed in serum samples. Moreover, sterol and metabolite profiling in serum and feces, microbiota modulation, anthropometric measurements and body composition, bioimpedance, dietary intake and physical activity questionnaire are evaluated. All parameters are evaluated at the beginning (weeks 0 and 14) and at the end of each intervention period (weeks 8 and 22).

Eligibility criteria: Inclusion Criteria:

* BMI: 27-29.9 or 30-39.9
* Plasmatic glucose: \< 100mg/dl or 100-125mg/dl
* Glycosylated hemoglobin: \< 5.7 or 5.7-6.4
* LDL cholesterol \> 115mg/dL
* Serum levels of biochemical and hematological parameters and fat-soluble vitamins within reference ranges.

Exclusion Criteria:

* Subjects on cholesterol-lowering pharmacological treatment
* Smokers
* Alcohol consumption above 30 g/day
* Pregnant or lactating women
* Any infection, serious illness or co-morbidity that may affect the bioavailability of PS (e.g., malabsorption, celiac disease, allergies or food intolerances)
* Diseases of the gastrointestinal tract
* Antibiotic, hormonal or anabolic treatment
* Participants consuming foods enriched with PS or food supplements that contain PS
* Participants who follow specialist weight loss diets, vegans or vegetarians

Primary outcomes:
measure: Changes in plasmatic LDL-c
timeFrame: 0, 8, 14 and 22 weeks
Secondary outcomes:
measure: Changes in plasmatic total cholesterol
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic HDL-c
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic non-HDL cholesterol
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic triglycerides
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic Apo A
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic Apo B
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic fibrinogen
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic High-sensitivity C-reactive protein (hsCRP)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic glucose
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic insulin
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum levels of the sterols and metabolites profile
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in feces levels of the sterols and metabolites profile
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum interleukin 10 (IL-10)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum interleukin 12p70 (IL-12p70)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum interleukin 1β (IL-1β)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum interleukin 6 (IL-6)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum interleukin 8 (IL-8)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum tumor necrosis factor alpha (TNFα)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum vascular cell adhesion molecule-1 (VCAM-1)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum E-Selectin
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum endothelin (ET-1)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in serum plasminogen activator inhibitor-1(PAI-1)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic LDL-cholesterol oxidation
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic 8-isoprostane
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic malondialdehyde (MDA)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in reduced glutathiones (GSH)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in oxidized glutathione (GSSG)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in the composition of microbiota in feces
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in feces of short-chain fatty acids (SCFAs)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in plasmatic levels of cholesterol oxidation products (COPs)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in body weight (WT)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in body height (HT)
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in body circumferences
timeFrame: 0, 8, 14 and 22 weeks
measure: Changes in Bioelectrical impedance analysis (BIA)
timeFrame: 0, 8, 14 and 22 weeks
measure: Assessment of dietary intake
timeFrame: 0, 8, 14 and 22 weeks
measure: Evaluation of the physical activity to measure quality of life
timeFrame: 0, 8, 14 and 22 weeks
measure: Evaluation of the Mediterranean diet adherence to measure quality of life
timeFrame: 0, 8, 14 and 22 weeks
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe de Valencia
Study officials:
affiliation: University of Valencia
name: Guadalupe Garcia Llatas, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Blanco-Morales V, Silvestre RLA, Hernandez-Alvarez E, Donoso-Navarro E, Alegria A, Garcia-Llatas G. Influence of Galactooligosaccharides on the Positive Effect of Plant Sterol-Enriched Beverages on Cardiovascular Risk and Sterol Colon Metabolism. J Agric Food Chem. 2022 Jan 19;70(2):532-542. doi: 10.1021/acs.jafc.1c06120. Epub 2022 Jan 11.
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