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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: Nutraceutical combination
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nutraceutical combination<br>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<br>* 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)<br>|
| Placebo Comparator: Placebo<br>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<br>* 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)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipids, Cholesterol, Triglycerides, Dyslipidemia, Low density lipoprotein cholesterol, Dietary Fats, Hyperlipidemias, Dietary Supplements, Food Supplements, Nutraceuticals, Nutriceuticals