Effects of Nutraceutical Therapies on Endothelial Function, Platelet Aggregation, and Coronary Flow Reserve

NCT02969070 | Completed

• 1 other identifier: FedericoIIU 259/16
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Hypercholesterolemia is considered one of the most important cardiovascular risk factors. Cardiovascular prevention include a class I indication to statins in addition to non-pharmacologic intervention and prevention strategies in patients deemed to be 'high risk'. Along with non-pharmacologic intervention and prevention strategies, newer approaches to reduce cholesterol blood levels currently include nutraceuticals, which are compounds derived from foods with cholesterol lowering actions. However, it remains unclear if nutraceuticals yield additive positive effects other than cholesterol lowering. In particular, there is evidence that Berberine has cardiovascular protective effects and that, in vitro, Morus Alba, mulberry fruit, modulates platelet function by inhibiting platelet activation, thromboxane formation, serotonin secretion, aggregation and thrombus formation. Furthermore, Morus Alba exerts an α-glucosidase inhibitory and antioxidant activity in vitro, which may reduce postprandial glucose peak, thus improving HbA1c concentration. Accordingly, we designated a study to evaluate the effects of two commercially available nutraceutical combined pills \[LopiGLIK™, Akademy Pharma, 1 capsule/day containing red yeast rice 220 mg (at least 3,3 mg of Monacolin K) + Berberine 531,25 mg + Morus Alba 200 mg (at least 4 mg of Deoxynojirimycin) vs. Armolipid Plus®, Meda Pharma, 1 capsule/day containing Berberis aristata d.e. 588 mg (equivalent to Berberine chloride 500 mg) + Red yeast rice 200 mg (equivalent to Monacolin K 3 mg) + Policosanol 10 mg + Folic acid 0.2 mg + Coenzyme Q10 2.0 mg + Astaxanthin 0.5 mg\] on lipid and metabolic profile, platelet aggregation, endothelial function and coronary flow reserve (CFR). For this purpose patients with hypercholesterolemia not requiring statins or statin intolerant at moderate cardiovascular risk will be subjected at day 0 and at day 28, after 4 weeks of therapy, to blood sampling to evaluate lipid and metabolic profile, peripheral arterial tonometry (EndoPAT), platelet aggregation tests with light transmission aggregometry (LTA), nitric oxide (NO) release, endothelial nitric oxide synthase (eNOS) phosphorylation on platelets. Only for CFR, patients will be further evaluated also after two hours from the administration of the first dose of nutraceutical combined pill. Patients will be randomly assigned to receive therapy with LopiGLIK™ or with Armolipid Plus®.

Conditions

Hypercholesterolemia; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (1)

• Effects on endothelial function as evaluated by Reactive Hyperemia Index (RHI)

  28 days

Secondary Outcomes (7)

• Evaluation of treatment tolerability

  28 days

• Reasons for treatment discontinuation

  28 days

• Effects on lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides)

  28 days

• Effects on metabolic indexes (glucose levels)

  28 days

• Effects on metabolic indexes [insulin plasma levels and insulin sensitivity index (HOMA index)]

  28 days

Study Arms (2)

LopiGLIK™ group

ACTIVE COMPARATOR

4 weeks of LopiGLIK™ therapy 1 capsule/day

Dietary Supplement: LopiGLIK™ therapy

Armolipid Plus group

ACTIVE COMPARATOR

4 weeks of Armolipid Plus therapy 1 capsule/day

Dietary Supplement: Armolipid Plus® therapy

Interventions

LopiGLIK™ therapy DIETARY_SUPPLEMENT

4 weeks of LopiGLIK™ therapy 1 capsule/day

LopiGLIK™ group

Armolipid Plus® therapy DIETARY_SUPPLEMENT

4 weeks of Armolipid Plus® therapy 1 capsule/day

Armolipid Plus group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years old
• Patients with hypercholesterolemia and moderate cardiovascular risk according to current ESC guidelines (risk of fatal cardiovascular event of 1-9% at 10 years according to SCORE risk charts of low-risk populations)
• Patients giving written Informed Consent.

You may not qualify if:

• Statin treatment indication
• Previous cardiovascular event
• Diabetes mellitus
• Creatinine Clearance \<60ml/min/1.73mm2
• Moderate to severe anemia Hb \< 10mg/dl
• Platelet count \>600 x 103/mm3 o \<150 x 103/mm3 o hematocrit (HCT) \>50% o \<25%

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

University of Naples "Federico II"

Naples, 80131, Italy

Location

Related Publications (6)

• Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available.

  PMID: 27222591 BACKGROUND

• Trimarco V, Izzo R, Stabile E, Rozza F, Santoro M, Manzi MV, Serino F, Schiattarella GG, Esposito G, Trimarco B. Effects of a new combination of nutraceuticals with Morus alba on lipid profile, insulin sensitivity and endotelial function in dyslipidemic subjects. A cross-over, randomized, double-blind trial. High Blood Press Cardiovasc Prev. 2015 Jun;22(2):149-54. doi: 10.1007/s40292-015-0087-2. Epub 2015 Apr 14.

  PMID: 25870124 BACKGROUND

• Carrizzo A, Ambrosio M, Damato A, Madonna M, Storto M, Capocci L, Campiglia P, Sommella E, Trimarco V, Rozza F, Izzo R, Puca AA, Vecchione C. Morus alba extract modulates blood pressure homeostasis through eNOS signaling. Mol Nutr Food Res. 2016 Oct;60(10):2304-2311. doi: 10.1002/mnfr.201600233. Epub 2016 Jun 27.

  PMID: 27234065 BACKGROUND

• Gargiulo P, Marciano C, Savarese G, D'Amore C, Paolillo S, Esposito G, Santomauro M, Marsico F, Ruggiero D, Scala O, Marzano A, Cecere M, Casaretti L, Perrone Filardi P. Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: a digital reactive hyperemia study. Int J Cardiol. 2013 Apr 30;165(1):67-71. doi: 10.1016/j.ijcard.2011.07.076. Epub 2011 Aug 17.

  PMID: 21851998 BACKGROUND

• Marciano C, Galderisi M, Gargiulo P, Acampa W, D'Amore C, Esposito R, Capasso E, Savarese G, Casaretti L, Lo Iudice F, Esposito G, Rengo G, Leosco D, Cuocolo A, Perrone-Filardi P. Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease. Eur J Nucl Med Mol Imaging. 2012 Jul;39(7):1199-206. doi: 10.1007/s00259-012-2117-9. Epub 2012 Apr 12.

  PMID: 22526959 BACKGROUND

• Esposito R, Sorrentino R, Giugliano G, Avvedimento M, Paolillo R, Santoro C, Scalamogna M, Esposito M, Ilardi F, Rozza F, Esposito G, Galderisi M, Trimarco V. Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve. Immun Ageing. 2018 Nov 22;15:30. doi: 10.1186/s12979-018-0138-3. eCollection 2018.

  PMID: 30479642 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Bruno Trimarco, MD

  Federico II University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 13, 2016
• First Posted: November 21, 2016
• Study Start: November 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: October 1, 2017
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

IT (1)