Efficacy and Tolerability of the Nutraceutical Formulation Coleosoma in Dyslipidemic Subjects

Study Overview
=================
Brief Summary
-----------------
The overall objective of the study is to assess the efficacy of Coleosoma formulation (fermented red rice, berberine and chitosan) in reducing non-HDL cholesterol in dyslipidemic patients.

Detailed Description
-----------------
The incidence of cardiovascular diseases related to atherosclerosis is the leading cause of death in industrialized countries and in many developing countries. It becomes, therefore, essential to implement preventive strategies with lifestyle changes in order to prevent / control the risk factors related to cardiovascular disease. Dyslipidemia is characterized by qualitative and quantitative alterations of plasma lipids and lipoproteins. In subjects where it is not yet indicated a statin therapy, the guidelines recommend a lifestyle (diet and exercise) act to control cardiovascular risk factors. The formulation Coleosoma is a supplement composed of fermented red rice, berberine and chitosan. Aim of the study is to evaluate the effectiveness of coleosoma formulation in reducing non-HDL cholesterol (Non-HDL-C), which provides a measure of the cholesterol content in all atherogenic particles. This is a single-center, randomized (3:1) and controlled double-blind phase II study that involve dyslipidemic patients with non-HDL cholesterol levels ≥ 160 mg / dl. The study included a maximum of 4 visits for all subjects enrolled. All eligible patients at V0 (screening) undergo baseline assessments (V1) and have been allocated according to the procedure of randomization to one of the study arms. Follow-up (FU) visits for all subjects was at 4 (V2) and at 12 weeks (V3) after randomization. Laboratory and diagnostic: At each visits patients undergo: anthropometric and hemodynamic assessment: weight and height for Body Mass Index (BMI) calculation, waist circumference, blood pressure, heart rate; blood collection for metabolic/hormonal profile: fasting plasma glucose, HbA1c, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), total gastric inhibitory polypeptide (GIP), total cholesterol, HDL-cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, creatine phosphokinase (CPK), apolipoprotein (Apo) B, Apo A1, and inflammatory cytokines (IL-1, IL-6, IL-10, high-sensitivity C Reactive Protein (hsPCR), TNFalpha). At V1 and V2 the Endothelial Progenitor Cells (EPC) number was evaluated with a cytofluorimetric assay. Safety analysis has been conducted after 12 weeks treatment by determining ALT, CPK and estimated Glomerular filtration rate (eGFR) values. This study has been sponsored by DOC generici s.r.l.

Official Title
-----------------
Randomized Controlled Clinical Trial for Assessing Tolerability and Effectiveness of Formula Coleosoma 29 in Patients With Dyslipidemia

Conditions
-----------------
Dyslipidemias

Intervention / Treatment
-----------------
* Dietary Supplement: Coleosoma
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: non-HDL cholesterol ≥ 160 mg/dl; providing their written Informed Consent; capable of understanding the nature, purpose and study procedures Exclusion Criteria: diabetes (ADA criteria) reduced renal (GFR<60 mL/min/1.73m2) or hepatic (transaminase levels >2.5 folds the upper reference limit) function; present or past history of alcohol or drug abuse cerebro-vascular and neoplastic diseases in the 5 years prior to study visit use of drugs or food supplements interfering with cholesterol levels pregnancy or breastfeeding; monogenic dyslipidemia; participation in other clinical trials in the previous 30 days; uncompensated hypothyroidism

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study included two arms: a treatment arm with dietary supplement (Coleosoma) and a placebo arm. Coleosoma is the name of a new patented dietary supplement composed by Berberin 200 mg, Fermented Red Rice from Monascus purpureus 100 mg (correspondiing at 3 mg of monacolin K), Chitosan 100 mg e Q10 Coenzyme10 mg
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: coleosoma<br>coleosoma 500mg tablet daily | Dietary Supplement: Coleosoma<br>* patients will take one tablet of 500mg daily for 12 weeks. No dose titration is foreseen.<br>* Other names: TegraDOC;|
| Placebo Comparator: placebo<br>placebo tablets | Dietary Supplement: Placebo<br>* patients will take one tablet daily for 12 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline values of non-HDL cholesterol (mg/dl) after 12 weeks of coleosoma treatment vs placebo | Difference in the non-HDL cholesterol value compared to baseline in the 2 arms. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline values of non-HDL cholesterol (mg/dl) at 4 weeks of coleosoma treatment vs placebo | Difference in the non-HDL cholesterol value compared to baseline in the 2 arms. | 4 weeks | 
| change from baseline values of Free Plasma Glucose (mg/dl) at 12 weeks of coleosoma treatment vs placebo | Difference in the Free Plasma Glucose value compared to baseline in the 2 arms. | 12 weeks | 
| change from baseline values of Body Mass Index (Kg/m2) at 12 weeks of coleosoma treatment vs placebo | Difference in the BMI value compared to baseline in the 2 arms. | 12 weeks | 
| change from baseline values of waist circumference (cm) at 12 weeks of coleosoma treatment vs placebo | Difference in the waist circumference value compared to baseline in the 2 arms. | 12 weeks | 
| Change from baseline values of HbA1C (%) at 12 weeks of coleosoma treatment vs placebo | Difference in the HbA1C value compared to baseline in the 2 arms. | 12 weeks | 
| Change from baseline values of LDL Cholesterol, triglycerides and HDL cholesterol at 12 weeks of coleosoma treatment vs placebo | Difference in theLDL Cholesterol, triglycerides and HDL cholesterol value compared to baseline in the 2 arms. All these parameters have the same Units of Measure (mg/dl) | 12 weeks | 
| Change from baseline values of ApoB/Apo A1 ratio at 12 weeks of coleosoma treatment vs placebo | Difference in the ApoB/Apo A1ratio compared to baseline in the 2 arms. | 12 weeks | 
| Change from baseline values of inflammatory cytokines (IL-1, IL6, IL-10, hsPCR, TNFalpha ) at 12 weeks of coleosoma treatment vs placebo | Difference in the inflammatory cytokines value compared to baseline in the 2 arms. All these parameters have the same Units of Measure (pg/ml) | 12 weeks | 
| Change from baseline values of insulin (pmol/l) at 12 weeks of coleosoma treatment vs placebo | Difference in the insulin value compared to baseline in the 2 arms. | 12 weeks | 
| Change from baseline values of hormone profile (glucagon, active GLP-1 and GIP) at 12 weeks of coleosoma treatment vs placebo | Difference in the hormone profile compared to baseline in the 2 arms. All these parameters have the same Units of Measure (pg/ml) | 12 weeks | 
| Change from baseline values of Endothelial Progenitor Cells (EPC) number at 12 weeks of coleosoma treatment vs placebo | Difference in the EPC number compared to baseline in the 2 arms. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dyslipidemia, dietary supplement