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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04698447
• Other study ID #: Natural Supplement CitraVes
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 28, 2019
• Est. completion date: February 2021

Study information

• Verified date: January 2021
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: February 2021
• Est. primary completion date: June 19, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers
• Metabolic Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Italy	University Hospital of Palermo	Palermo

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Corrado C, Raimondo S, Chiesi A, Ciccia F, De Leo G, Alessandro R. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sci. 2013 Mar 6;14(3):5338-66. doi: 10.3390/ijms14035338. — View Citation

Ju S, Mu J, Dokland T, Zhuang X, Wang Q, Jiang H, Xiang X, Deng ZB, Wang B, Zhang L, Roth M, Welti R, Mobley J, Jun Y, Miller D, Zhang HG. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol Ther. 2013 Jul;21(7):1345-57. doi: 10.1038/mt.2013.64. Epub 2013 Jun 11. — View Citation

Lakkaraju A, Rodriguez-Boulan E. Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol. 2008 May;18(5):199-209. doi: 10.1016/j.tcb.2008.03.002. Epub 2008 Apr 7. Review. — View Citation

Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Crit Rev Food Sci Nutr. 2017 Feb 11;57(3):613-631. Review. — View Citation

Martínez-Abundis E, Méndez-Del Villar M, Pérez-Rubio KG, Zuñiga LY, Cortez-Navarrete M, Ramírez-Rodriguez A, González-Ortiz M. Novel nutraceutic therapies for the treatment of metabolic syndrome. World J Diabetes. 2016 Apr 10;7(7):142-52. doi: 10.4239/wjd.v7.i7.142. Review. — View Citation

Raimondo S, Naselli F, Fontana S, Monteleone F, Lo Dico A, Saieva L, Zito G, Flugy A, Manno M, Di Bella MA, De Leo G, Alessandro R. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget. 2015 Aug 14;6(23):19514-27. — View Citation

Wang B, Zhuang X, Deng ZB, Jiang H, Mu J, Wang Q, Xiang X, Guo H, Zhang L, Dryden G, Yan J, Miller D, Zhang HG. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Mol Ther. 2014 Mar;22(3):522-534. doi: 10.1038/mt.2013.190. Epub 2013 Aug 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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