The Role of a Natural Product, Containing Nanovesicles From Citrus Limon (L.) Juice, on Different CV Risk Factors

Study Overview
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Brief Summary
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Clinical trial about beneficial effects of natural supplement in a spray-dried formulation, citraVes™, obtained from Citrus Limon (L.) juice on general body health.

Detailed Description
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This is one randomized, double-blind, placebo-controlled study. The aim of the present study is to investigate the role of a natural product, citraVes™ on several cardiovascular risk factors. The research hypothesis is to evaluate whether this natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice (Navhetec S.R.L., Palermo, Italy) may improve different cardio-metabolic parameters in subjects with the metabolic syndrome. All subjects will be evaluated at baseline, after 1 month and after 3 and 6 months of supplementation with natural product or placebo.

Official Title
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Effects of the Natural Supplement CitraVes Containing Nanovesicles Delivered From Citrus Limon (L.) Juice on Cardio-metabolic Risk Factors in Subjects With Metabolic Syndrome

Conditions
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Metabolic Syndrome, Healthy Volunteers

Intervention / Treatment
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* Dietary Supplement: Natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice_MetS
* Dietary Supplement: Placebo (without any active ingredients)
* Dietary Supplement: Natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice_HS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men and women > 18 years old; body mass index (BMI) > 25 kg/m²; subjects who are able to swallow; subjects who are willing to participate in the study and therefore, to sign informed consent prior to any study procedure; the inclusion criteria for patients with MetS was also the diagnosis of MetS, as defined by international consensus [Alberti KG, et al. Circulation. 2009; 120:1640-5]. Exclusion Criteria: pregnancy or the willingness to become pregnant; severe renal or hepatic impairment; known severe infections (such as HIV, HBV, HCV) any neoplasms; the exclusion criteria for healthy volunteers were also diagnosis of any one of the following diseases: hypertension, diabetes mellitus, dyslipidaemia or metabolic diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Supplement blinded<br>20 subjects with the metabolic syndrome receiving natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice (1000 mg/day) | Dietary Supplement: Natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice_MetS<br>* 20 eligible subjects with the metabolic syndrome (MetS) will take natural supplement containing a spray-dried formulation of citraVes™, directly in the mouth, without water, to be dissolved preferably under the tongue, at a stable dose of one sachet a day (1000 mg/day) for 6 months and as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study.<br>|
| Placebo Comparator: Placebo blinded<br>20 subjects with the metabolic syndrome receiving placebo (without any active ingredients) | Dietary Supplement: Placebo (without any active ingredients)<br>* 20 eligible subjects with the metabolic syndrome will take placebo in a spray-dried formulation (without any active ingredients) directly in the mouth, without water, to be dissolved preferably under the tongue, at a stable dose of one sachet a day for 6 months, as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study.<br>|
| Active Comparator: Dietary Supplement open-label<br>20 healthy volunteers receiving natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice (1000 mg/day) | Dietary Supplement: Natural supplement containing nanovesicles delivered from Citrus Limon (L.) juice_HS<br>* 20 eligible healthy subjects (HS) will take natural supplement containing a spray-dried formulation of citraVes™, directly in the mouth, without water, to be dissolved preferably under the tongue, at a stable dose of one sachet a day (1000 mg/day) for 6 months, maintained at fixed doses for the entire study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Plasma Lipids in Healthy Subjects | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) (mmol/l). | 3 months | 
| Change from Baseline in Plasma Lipids in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) (mmol/l). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Waist Circumference in Healthy Subjects | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on waist circumference (cm). | 3 months | 
| Change from Baseline in Waist Circumference in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on waist circumference (cm). | 6 months | 
| Change from Baseline in Body Mass Index (BMI) in Healthy Subjects | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on body weight (kg) and height (m) that will be combined to report BMI in kg/m^2. | 3 months | 
| Change from Baseline in Body Mass Index (BMI) in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on body weight (kg) and height (m) that will be combined to report BMI in kg/m^2. | 6 months | 
| Change from Baseline in Glycemia in Healthy Subjects | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on plasma glycemia (mmol/l). | 3 months | 
| Change from Baseline in Glycemia in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on plasma glycemia (mmol/l). | 6 months | 
| Change from Baseline in Glycated Haemoglobin in Healthy Subjects | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on glycated haemoglobin (HbA1c) (%). | 3 months | 
| Change from Baseline in Glycated Haemoglobin in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on glycated haemoglobin (HbA1c) (%). | 6 months | 
| Change from Baseline in Subclinical Atherosclerosis in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) (mm). | 6 months | 
| Change from Baseline in Plasma Cytokines in Subjects with Metabolic Syndrome | Effect of natural supplement containing nanovesicles from Citrus Limon (L.) juice on plasma cytokines (inflammatory markers) (pg/ml), that will be assessed using available enzyme-linked immunosorbent assay (ELISA) kits. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular risk, extracellular vesicles, metabolic parameters, nutraceuticals, Citrus limon (L.)