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

Not Applicable

Completed

Conditions: Hypercholesterolemia

Interventions: Other: Placebo
Dietary Supplement: Nutraceutical combination

Registration Number: NCT03739242

Lead Sponsor: A. Menarini Industrie Farmaceutiche Riunite S.r.l.

Brief Summary: 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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 88

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Nutraceutical combination	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Blood Triglycerides Level	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in blood triglycerides level from randomization (day 0) to V4 (week 8)
Change in Blood Apolipoprotein B Level	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in blood apolipoprotein B level from randomization (day 0) to V4 (week 8)
Change in Total LDL Cholesterol/HDL Cholesterol Ratio	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in LDL/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)
Change in Blood HDL Cholesterol Level	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in blood HDL cholesterol level from randomization (day 0) to V4 (week 8)
Change in Blood Non-HDL Cholesterol Level	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in blood non-HDL cholesterol level from randomization (day 0) to V4 (week 8)
Change in Serum Creatinine	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in Serum Creatinine values from randomization (day 0) to V4 (week 8)
Change in Total Cholesterol/HDL Cholesterol Ratio	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in total cholesterol/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)
Change in Total Blood Cholesterol Level	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in total blood LDL cholesterol level from randomization (day 0) to V4 (week 8)
Change in Serum Uric Acid	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in Serum uric acid values from randomization (day 0) to V4 (week 8)
Change in Creatine Phosphokinase (CPK)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in creatine phosphokinase (CPK) from randomization (day 0) to V4 (week 8)
Change in Pulse Volume (PV) Waveform (Endothelial Reactivity)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	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).
Change in Glycemia	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in Glycemia from randomization (day 0) to V4 (week 8)
Change in Aspartate Aminotransferase (AST)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)
Change in Alanine Aminotransferase (ALT)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)
Change in Gamma Glutamyl Transpeptidase (GGT)	From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment	Mean change gamma glutamyl transpeptidase (GGT) from randomization (day 0) to V4 (week 8)