Efficacy and Safety of Nutraceuticals (Bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) in Patients With Diabetes Mellitus Type II and Dyslipidemia.
Efficacy and Safety of Nutraceuticals (Bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) in Patients With Diabetes Mellitus Type II and Dyslipidemia.
The presence of dyslipidemia, is a significant cardiovascular risk factor. This factor, however, determines the three-fold increase in cardiometabolic risk when an isolated or mixed dyslipidemia is associated with the presence of diabetes mellitus. Diabetes mellitus is a metabolic alteration resulting in a decrease in insulin secondary to reduced availability of this hormone or an impediment to its normal action or a combination of these factors. . Under normal conditions, the vascular endothelium responds to short-term increases in flow by releasing NO and other endothelium-dependent relaxing factors that dilate the artery. Flow-mediated dilation(FMD) is impaired in atherosclerotic coronary arteries. The supplementation with polyphenols of olive leaves, bergamot extract, gymnema sylvatic extract (gymnemic acid) and phaseolamin (bean protein) significantly improves the glico-lipid balance through an improvement in liver function, an inhibition to more levels of lipid metabolism .
Recently, it has been documented how the polyphenolic fraction extracted from bergamot (BPF) administered orally both in animal models with induced hyperlipidemia diet, and in patients with metabolic syndrome, produces a significant and substantial reduction of serum cholesterol, triglycerides and blood levels of glucose. This effect was accompanied by an important improvement in vascular reactivity in patients with hyperlipidemia and high blood sugar, suggesting the potential protective role of BPF in patients with metabolic syndrome and elevated cardiovascular risk.
Oleuropeina (Olea Europaea) is also characterized by a peculiar polyphenolic profile. Both fruits and leaves, thanks to their cardioprotective activity, are used as antihypertensive agents and in the treatment of vascular disorders. The gymnemic acid (glycosidic triterpene), extracted from the leaves of Gymnema Sylvestre, is the representative element of the plant. Thanks to its presence in the phytocomplex, it carries out a hypoglycaemic action through two main mechanisms: inhibition of intestinal sugar absorption and increased metabolic transformation of glucose at the cellular level.
To better define the interrelations of systemic CRFs, FMD, and effects of chronic nutraceutical supplements we performed clinical evaluations and ultrasound measurements of the flow and diameter responses to forearm cuff occlusion in a large, well characterized community-based cohort.
Primary end point Effectiveness To demonstrate in diabetic patients,the effectiveness of nutraceuticals (bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) to reduce total and LDL cholesterol.
Secondary end points To demonstrate in diabetic patients,the effectiveness of nutraceuticals (bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) to improve Endothelial function evaluated with vascular Doppler color echo; CHARACTERISTICS OF THE POPULATION diabetic patients in optimized medical therapy and increased plasma levels of total and LDL cholesterol EXPERIMENTAL DESIGN AND METHODOLOGY OF RESEARCH Experimental drawing Phase II prospective, randomized, comparative, vs placebo study Sample size Literature data show that total cholesterol levels> 200 mg / dl and LDL> 130 mg//dl have an increased cardiovascular risk in subjects with diabetes mellitus; in the Calabrian people the Health Examination Survey conducted in 2012, showed the following average values: total cholesterolemia 233 +/- 45 mg /dl for men and 238 +/- 40 mg / dl for women; while for LDL cholesterol the mean values are respectively 151 +/- 30 mg / dl in humans and 148 +/- 35 mg / dl in women. In these subjects the doubling of the statin dosage contributes to a further reduction of plasma levels by about 6%; the hypothesis not evaluated is that the integration with nutraceuticals (bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) in patients with optimized therapy, involves reduction of plasma levels> 6% HYPOTHESIS N =2(1600)/(196)*6,2= 3200/196*6.2= 88 The study will be performed with the enrollment of 88 diabetic patients, Eligible patients will be of both sexes, and naïve patients on nutraceutical (920 mg), consequently recruited.
Patients using randomization tab will be randomized 1: 1 to treatment with active substance versus placebo. Investigators may not be aware of the sequence in which the treatments will be assigned nor foresee the next assignment in any way.
TIMING OF THE STUDY The duration of the study will be 12 weeks after recruitment. After signing the informed consent, previously approved by the Ethics Committee, the subjects can fully enter the study. Each patient must make three visits: SEL (selection visit); V01 (initial visit); TERM (final visit). Excluding the patient's inclusion visit (V01), each visit will take place in the morning and each patient will be studied at the same time of day, between 8.00 am and 12.00 am, during the study (± 2 hours).
The treatment is always accompanied by main meals. The first administration in naïve patients on Nutraceuticals will be done under the supervision of the staff involved in the study. Patients will then be reviewed at 4 and 12 weeks after recruitment.
ANALYTICAL PRESENTATION OF THE PROCEDURES TO BE PERFORMED Before signing informed consent, patients will be informed about the rationale of the study, the objective and the procedures of the study itself. All the subjects can refuse to participate, or they can interrupt the participation at any time.
The study will be conducted in accordance with the protocol, Good Clinical Practice (GCP) and according to the regulatory principles of application.
Selection visit During the selection visit (SEL), all patients are subjected to the following evaluation.
All laboratory results and pregnancy tests are checked before enrolling the patient in the study:
If the result of these evaluations:
A) Does not meet the inclusion criteria, the investigator must:
Therefore, the patients eligible for the study will be recruited and treated with:
During the 4-week visit (V01), patients undergo:
During the final visit (TERM), made twelve weeks after enrollment (± 3 days), patients undergo the evaluation of:
Two copies of the written consent will be dated and signed by the investigator. All data will be collected in the case report (CRF) INTERRUPTION OF THE TREATMENT Withdrawal and interruption of a patient's study A patient can withdraw from the study at any time.
The treatment may be prematurely and permanently interrupted by the investigator for one or more of the following reasons:
In case of premature interruption of treatment:
- the investigator must document the reason (s) and the exact time of the interruption of the study in the CRF and in the patient's record. If more than one reason is given, the investigator must indicate the main one.
In the case of a premature withdrawal from the study due to an adverse event (an event requiring immediate notification or not), the investigator must collect all the information related to the event. If necessary, the information is put together later.
- During the final follow-up visit, the investigator must:
ADVERSE EVENTS AND ADVERSE REACTIONS Serious adverse event and adverse drug reactions The European legislation on pharmacovigilance was amended with the adoption in 2010 of EU Regulation 1235/2010, whose application is operational from 2 July 2012, and of Directive 2010/84 / EU, in force since 21 July 2012.
Collection and notification, by the individual Investigators and by the Promoter, of adverse events / adverse reactions occurred to patients enrolled in clinical trials with medicinal products for human use. For the definition of serious and non-serious adverse events, refer to the Standards of Good Clinical Practice of the PATIENT TREATMENTS Treatment management There is only one treatment period, and the formulation of the drug is in capsule form. The treatment is provided directly by the investigator at the end of each scheduled visit. Patients will take the product in a single daily dose after one of the main meals.
Delivery of treatment
Patients will be divided into two groups:
Group 1 composed of 45 enrolled subjects who will receive placebo bis in die, twenty minutes before the main meals; Group 2 composed of 45 subjects enrolled with type II diabetes mellitus and hypercholesterolemia without hypertriglyceridemia who will receive a double administration of nutraceuticals (bergamot 450 mg, Gymnema (400 mg, Phaseolamin 30 mg, Olea Europaea 10 mg) mg with the cadences described for group 1; Previous and concurrent treatments All details on previous and concurrent treatments must be collected by the investigator in an appropriate form in the CRF. It will be the duty of the investigator to always evaluate that concomitant and / or previous treatments are authorized and included in the inclusion criteria.
STATISTICAL ANALYSIS All values are expressed as mean +/- Standard deviation. The values of the selected variables in perspective mode will be expressed as mean +/- standard deviation (parametric variables) or median (non parametric variables). To compare the differences between the study groups, correlation analysis, t-test for samples, independent, chi-square test, frequency tables, cross tables and tables for multiple / dichotomous responses will be used. A probability value <0.05 will be considered statistically significant.
Inclusion Criteria:
All concomitant treatments should have started at least 3 months before the start of the study and should be kept at a constant dose throughout the study.
Exclusion Criteria: