Effect of a Treatment With a Nutraceutical Combination on Sub-optimal LDL Cholesterol Levels (NATCOL)

A Randomized, Double-blinded, Placebo-controlled, Clinical Study of the Effects of a Nutraceutical Combination on LDL Cholesterol Levels in Subjects With Sub-optimal Blood Cholesterol Levels

High cholesterol is one of the major controllable risk factor for coronary heart disease. It is well demonstrated that drugs that reduce the intestinal absorption of cholesterol or block the synthesis of cholesterol or the association of both, can reduce cholesterol and reduce rate of cardiovascular events. The trial will evaluate natural alternative to this drug approach testing the effects of a combination of phytosterol, a nutritional that reduce cholesterol absorption, and fermented red rice, a nutritional that reduce the synthesis of cholesterol. Subjects with sub optimal blood cholesterol levels, matching all the inclusion criteria and none of the exclusion criteria, will be treated for 8 weeks with a nutraceutical combination of phytosterols and fermented red rice and will have to maintain, during the entire duration of the study, the Mediterranean-style diet provided. The study will evaluate as primary objective the changes in LDL cholesterol blood levels and more in general the modulation of lipid profile and of others clinical parameters as well as the tolerability.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Dietary supplement: Nutraceutical combination; Other: Placebo

Detailed Description

The study is made up of four visits distributed over a 10-weeks period:

V 1 (day -14) - Screening: After providing written informed consent, tests will be run in order to check the subject's eligibility for the study. Subjects will also be given suggestions regarding their diet (a Mediterranean-style diet is to be maintained for the entire duration of the study).

V2 (baseline) and Day 0 (randomization): After confirmation of the subject's eligibility [LDL-C and Triglycerides (TG) criteria confirmed with blood test results], eligible subjects will be randomized within 3 days to one of the two treatment groups. During this visit an endothelial reactivity test will be performed.

V3 (28 ±3 days after Day 0) - Intermediate: Blood will be drawn for tests and compliance with treatment will be assessed. V4 (28 ± 3 days after Visit 3) - End of study: Blood tests and an endothelial reactivity test will be performed and treatment compliance will be assessed.

Weight, waist circumference, Index of Central Obesity (ICO) and Body Mass Index (BMI), Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) will be measured/calculated at each visit, height at Visit 1.

Heart rate and blood pressure will be measured at each visit. Adverse events (AEs) will be collected throughout the study starting from the Informed consent signature.

The study will be monitored according to the details specified in the Monitoring Plan. The monitor will have the responsibility of reviewing the ongoing study with the Investigator to verify adherence to the protocol and to deal with any problems. Case Report Form (CRF) will be checked for completeness and consistency with the source data and special attention will be dedicated to patient enrolment, obtaining signed informed consent, occurrence of AEs, product accountability, and accurate recording of variables. The confidentiality of study related documents shall be maintained at all times. The Investigator agrees to allow access to all study materials needed for the proper review of study conduct.

An independent quality audit/inspection at the study site may take place at any time during or after the study. The independent audit/inspection can be carried out by the Sponsor's independent Quality Assurance (QA), by a Health Authorities or an Ethics Committee (EC).

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Policlinico S.Orsola - Malpighi Medicina Interna Borghi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-

Subjects must meet all of the following inclusion criteria:

• Age 30-75 years
• LDL-cholesterol = 115 -190 mg/dL
• Triglycerides < 400 mg/dL
• Any cardiovascular therapy should be stable for type and dose for at least three months
• Signed, written informed consent

Exclusion Criteria:

-

Subjects must meet none of the following exclusion criteria:

• Intolerance to any ingredient of dietary supplement
• Patients already suffering from cardiovascular diseases or at high risk of developing cardiovascular diseases
• Myopathies
• Uncontrolled diabetes mellitus based on PI judgment
• Chronic renal failure [defined as estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2] or liver failure [defined as aspartate aminotransferase (AST) and /or Alanine Aminotransferase (ALT) >3 upper limit of normal (ULN)]
• Body Mass Index > 32 kg/m2
• Therapy with statins or other drugs or supplements with effects on lipid metabolism
• Patients with acquired immunodeficiency
• Treatment with immunosuppressants
• Pregnant or breastfeeding women
• Women of childbearing potential not willing to use effective birth control methods
• Patients participating or having participated in another clinical trial within the previous 3 months
• Current or recent history of drug or alcohol addiction based on PI judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nutraceutical combination; One film-coated tablet (1300 mg) per os per day to be taken in the evening. Each tablet contains phytosterols 800 mg, Monascus purpureus (167 mg) titrated at 3% in monacolin K (5 mg), niacin 27 mg, linear aliphatic alcohols titrated to 60% octacosanol.	Dietary supplement: Nutraceutical combination; One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3)
Placebo Comparator: Placebo; One film-coated tablet (1300 mg) per os per day to be taken in the evening. Placebo tablets identical in appearance, size, shape, weight and taste to the active product.	Other: Placebo; One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood LDL Cholesterol Level	Mean change in blood LDL cholesterol level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Blood Cholesterol Level	Mean change in total blood LDL cholesterol level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Blood HDL Cholesterol Level	Mean change in blood HDL cholesterol level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Blood Non-HDL Cholesterol Level	Mean change in blood non-HDL cholesterol level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Blood Triglycerides Level	Mean change in blood triglycerides level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Blood Apolipoprotein B Level	Mean change in blood apolipoprotein B level from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Total Cholesterol/HDL Cholesterol Ratio	Mean change in total cholesterol/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Total LDL Cholesterol/HDL Cholesterol Ratio	Mean change in LDL/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Pulse Volume (PV) Waveform (Endothelial Reactivity)	Mean change in Pulse Volume (PV) waveform from randomization (day 0) to V4 (week 8). PV unit of measurement is a percent change in the PV waveform area, comparing waveforms during and before hyperemia through the equation √PV2/PV1 that relates PV at baseline (PV1) and PV during hyperemia (PV2).	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Glycemia	Mean change in Glycemia from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Aspartate Aminotransferase (AST)	Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Alanine Aminotransferase (ALT)	Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Gamma Glutamyl Transpeptidase (GGT)	Mean change gamma glutamyl transpeptidase (GGT) from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Serum Creatinine	Mean change in Serum Creatinine values from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Serum Uric Acid	Mean change in Serum uric acid values from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Change in Creatine Phosphokinase (CPK)	Mean change in creatine phosphokinase (CPK) from randomization (day 0) to V4 (week 8)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment

Collaborators and Investigators

• Sponsor: A. Menarini Industrie Farmaceutiche Riunite S.r.l.
• Investigators: Principal Investigator: Claudio Borghi, Professor, Policlinico S.Orsola - Malpighi Medicina Interna Borghi

Publications and helpful links

General Publications

• Cicero AFG, D'Addato S, Borghi C. A Randomized, Double-Blinded, Placebo-Controlled, Clinical Study of the Effects of a Nutraceutical Combination (LEVELIP DUO(R)) on LDL Cholesterol Levels and Lipid Pattern in Subjects with Sub-Optimal Blood Cholesterol Levels (NATCOL Study). Nutrients. 2020 Oct 14;12(10):3127. doi: 10.3390/nu12103127.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2017
• Primary Completion (Actual): August 29, 2018
• Study Completion (Actual): August 29, 2018

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cholesterol; Dyslipidemia; Lipids; Dietary Supplements; Triglycerides; Hyperlipidemias; Nutraceuticals; Low density lipoprotein cholesterol; Dietary Fats; Food Supplements; Nutriceuticals
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: MEIF/MOF-Col/001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No