Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Hypercholesterolemia

Study Overview
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Brief Summary
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The joint ESC/EAS guidelines for the management of dyslipidaemias recommend, for patients at low/moderate CV risk with raised LDL-C, a set of measures collectively defined as lifestyle interventions, with use of drugs only if the LDL-C levels cannot be controlled with such lifestyle interventions. Lifestyle interventions also includes food supplements. The reason is the following: a simple dietary advice has been shown (Cochrane review and meta-analysis, Rees et al, 2013) to achieve a modest reduction of total-C and LDL-C. The review reports: Dietary advice reduced total serum cholesterol by 0.15 mmol/L (95% CI 0.06 to 0.23) and LDL cholesterol by 0.16 mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months. An average reduction of LDL-C by 0.16 mmol/L (6.2 mg/dL) is definitely insufficient to control the level of LDL-C in those subjects. Therefore, those subjects would lose motivation to keep dieting. In this context, use of supplements would significantly amplify the result of diet. A significant proportion of ischemic cardiovascular events are believed to be supported by the coexistence of traditional cardiovascular risk factors such as diabetes, hypertension, dyslipidemia, smoking, and others. The aggregation of these factors is accompanied by a significant increase in the risk of cardiovascular events. Observational studies shown the existence of a relationship between cholesterolemia and coronary heart disease, clearly showing that subjects with even modestly increased total cholesterol values over time develop both fatal and non-fatal vascular events with a higher frequency compared to subjects with similar characteristics, but with lower basal values of cholesterol. Numerous controlled intervention studies, on the other hand, have shown that there is a close correlation between cholesterol reduction and cardiovascular risk; in fact, reductions in the plasma concentration of total and LDL-C, obtained through lifestyle modification or specific drugs, result in reductions in the incidence of major coronary events. The effectiveness of these interventions has been demonstrated both in subjects in primary prevention and in patients in secondary prevention.

Official Title
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Evaluation of the Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Moderately Hypercholesterolemic Subjects: a Double-blind, Placebo-controlled, Randomized, Clinical Trial

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: Dietary supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects agree to participate in the study and having dated and signed the informed consent form. Subjects who have the capability to communicate, to make themselves understood, and to comply with the study's requirements. Male or female aged ≥ 18 years and ≤ 70 years old. LDL-Cholesterol plasma levels >115 mg/dL and < 190 mg/dL. TG<400 mg/dL. Subjects who, according to the SCORE charts, have a low or moderate cardiovascular risk (defined as a total cardiovascular risk < 5%) and for whom, according to ESC/EAS guidelines 2012, the intervention strategy does not require a pharmacological lipid-lowering intervention. Exclusion Criteria: Subjects already affected by cardiovascular diseases (secondary prevention) or with estimated 10 years cardiovascular disease risk> 5%; Obesity (BMI>30 kg/m2) or diabetes mellitus; Assumption of lipid lowering drugs or food supplements, or drugs potentially affecting the lipid metabolism; Antihypertensive treatment not stabilized since at least 3 months; Anticoagulants therapy Uncontrolled hypertension (systolic blood pressure> 190 mmHg or diastolic arterial pressure> 100 mmHg); Known current thyroid, gastrointestinal or hepatobiliary diseases; Any medical or surgical condition that would limit the patient adhesion to the study protocol; Abuse of alcohol or drugs (current or previous); History of malignant neoplasia in the 5 years prior to enrolment in the study; History or clinical evidence of inflammatory disease such as severe arthritis, systemic lupus erythematosus or chronic inflammatory diseases or current therapy with immunosuppressive agents or long-term glucocorticoids; History or clinical evidence of any significant concomitant disease that could compromise the safety of the subject or the possibility of completing the study; Known previous intolerance to the tested nutraceutical Women in fertile age not using consolidated contraceptive methods Pregnancy and Breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator<br>Dietary supplement | Dietary Supplement: Dietary supplement<br>* Dietary supplement formulated with 400 mg Bergamot d.e. obtained from different parts of the Citrus Bergamot whole fruit (Citrus bergamia Risso et Poiteau, fructus), specifically from fresh fruits collected from November to February (Brumex TM). Oral administration: 1 tablet/day at evening meal<br>|
| Placebo Comparator: Placebo comparator<br>Placebo | Other: Placebo<br>* Oral administration: 1 tablet/day at evening meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-cholesterolemia absolute reduction from baseline and between groups | Absolute reduction of LDL-cholesterolemia after 12 weeks of treatment | 12 weeks | 
| LDL-cholesterolemia % reduction from baseline and between groups | % reduction of LDL-cholesterolemia after 12 weeks of treatment | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios | Absolute reduction of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment | 12 weeks | 
| % reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios | % reduction of of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment | 12 weeks | 
| % reduction from baseline and between groups in anthropometric parameters | % reduction of body mass index after 12 weeks of treatment | 12 weeks | 
| % reduction from baseline and between groups in blood pressure levels | % reduction of systolic and diastolic blood pressure after 12 weeks of treatment | 12 weeks | 
| Absolute reduction from baseline and between groups in blood pressure levels | Absolute reduction of systolic and diastolic blood pressure after 12 weeks of treatment | 12 weeks | 
| Absolute reduction from baseline and between groups in anthropometric parameters | Absolute reduction of body mass index after 12 weeks of treatment | 12 weeks | 
| % reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels | % reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment | 12 weeks | 
| Absolute reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels | Absolute reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment | 12 weeks | 
| Absolute reduction from baseline and between groups in liver parameters | Absolute reduction of GOT, GPT and gamma-GT after 12 weeks of treatment | 12 weeks | 
| % reduction from baseline and between groups in liver parameters | % reduction of GOT, GPT and gamma-GT after 12 weeks of treatment | 12 weeks |