Conjugated Linoleic Acid / Leucine Versus Metformin on Visceral Fat in Metabolic Syndrome

Study Overview
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Brief Summary
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In Mexico, obesity is a major public health problem. In recent years he has presented a considerable increase in the population. As a result, it has triggered a proportional increase in the incidence of cardiovascular disease and the development of Metabolic Syndrome (METS). Abdominal obesity is one of the main components of METS which is generally associated with insulin resistance / hyperinsulinemia. This is influenced both by the subcutaneous adipose tissue as visceral adipose tissue. There is evidence that the visceral fat has an important bearing on many factors of METS, like: glucose intolerance, hypertension, dyslipidemia, and insulin resistance. For management it requires a multidisciplinary approach, including changes in lifestyle, psychological and nutritional intervention as well as pharmacological and non-pharmacological support. Among non-pharmacological therapies, there is recently the use of Conjugated Linoleic Acid (ACL) and leucine where in its assigned properties include weight reduction, anti-atherogenic , hypocholesterolemic and immunostimulant effect and anticarcinogenic properties. Regarding weight reduction dominates the mechanism of action anti-lipolytic effect. But, studies are needed to link this consumption with the increase or decrease on visceral fat in individuals with METS.

Detailed Description
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The main objective is to compare the effect of the administration of ACL/Leucine vs. Metformin on visceral fat area in patients with METS. We will conduct a double-blind trial, randomized, on 4 groups, each group with 26 male and female patients of 35-65 years of age with METS diagnosed by IDF criteria. Randomization will determine who will receive the intervention during 8 week trial, each group will be like: Group (A) intervention with ACL/Leucine plus Metformin: 26 individuals will receive ACL/Leucine in a dosis of 2,475mg per 24 hrs (1,650mg or 2 capsules with the first meal and 825 mg or 1 capsule with the second meal) plus Metformin in a dose of 500 mg per day (with the first bite of the second meal) during 8 weeks. Group (B) Metformin plus Placebo of ACL/Leucine: 26 individuals will receive Metformin in a dose of 500 mg per day (with the first bite of the second meal) plus homologue placebo of ACL/Leucine (linseed oil capsules) in a dosis of 3600 mg each 24 hrs (2 capsules of 2400 mg with the first meal and 1200 mg or 1 capsule with the second meal) during 8 weeks. Group (C) ACL/Leucine plus Metformin's Placebo: 26 individuals will receive ACL/Leucine in a dose of 2,475mg per 24 hrs (1,650mg or 2 capsules with the first meal and 825 mg or 1 capsule with the second meal) plus homologate placebo of metformin (calcined magnesia) in a dose of 500 mg per day (with the first bite of the second meal) during 8 weeks. Group (D) Placebo of ACL/Leucine plus Placebo of Metformin: homologate placebo of ACL/Leucine (linseed oil capsules) in a dose of 3600 mg each 24 hrs (2 capsules of 2400 mg with the first meal and 1200 mg or 1 capsule with the second meal) plus homologated placebo of metformin (calcined magnesia capsules) in a dosis of 500 mg per day (with the first bite of the second meal) during 8 weeks. The clinical findings and laboratory test include a metabolic profile and biosafety, which will be baseline and at 8 weeks. Visceral fat area, epicardial fat, body weight, body fat, body mass index (BMI) and blood pressure will be determined during the inicial and final visit, likewise, hemodynamics parameters of arterial stiffness like aortic pulse wave velocity (PWVao), central pulse pressure (PPao), aortic augmentation index (IAxao) and central systolic blood pressure (cSBP) by an oscillometric monitoring system via BPLab ®. Adverse events and adherence to treatment will be documented. Statistical analysis: Mann-Whitney U Test and Wilcoxon exact test. It is considered with significance at p<0.05.

Official Title
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Effect of the Administration of Conjugated Linoleic Acid / Leucine Plus Metformin on Visceral Fat in Patients With Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: Conjugated linoleic acid/Leucine
* Drug: Metformin
* Dietary Supplement: Placebo of ACL/Leucine
* Other: Placebo of Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metabolic syndrome by IDF criteria: Central obesity (defi ned as waist circumference* with ethnicity specifi c values)≥80 cm in females and ≥90 cm in males plus any two of the following four factors: Raised triglycerides ≥ 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality Reduced HDL colesterol < 40 mg/dL (1.03 mmol/L) in males < 50 mg/dL (1.29 mmol/L) in females or specifi c treatment for this lipid abnormality Raised blood pressure systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg or treatment of previously diagnosed hypertension Raised fasting plasma glucose (FPG) ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes Stable body weight in the last 3 months Written informed consent Exclusion Criteria: Ascitis With previous abdominal surgery Pathologies that course with abdominal wall edema fluid retention Paniculitis of reumatic origin or any other ethiology Reumatic pathologies Metalic prothesis Previous known allergy to any of the ingredients that make up the active treatments assigned Known problem of fat absortion, esteatorrea, lipase deficiency, malabsortion of intestinal problems, CUCI

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: cojugated ALC/Leucine+Metformin<br>Intervention with conjugated linoleic acid/Leucine + 500mg in individuals with METS | Dietary Supplement: Conjugated linoleic acid/Leucine<br>* Conjugated linoleic acid/Leucine capsules, 825mg time daily with the first bite of eat meal during 12 weeks.<br>* Other names: UKN;Drug: Metformin<br>* Metformin in a dosis of 500mg per day (with the first bite of the second meal) during 12 weeks<br>* Other names: Predial plus;|
| Active Comparator: Metformin+placebo conjugatedALC/leucine<br>active comparator with Metformin 500mg + Placebo of ACL/Leucine in individuals with METS | Drug: Metformin<br>* Metformin in a dosis of 500mg per day (with the first bite of the second meal) during 12 weeks<br>* Other names: Predial plus;Dietary Supplement: Placebo of ACL/Leucine<br>* Homologate placebo of ACL/Leucine (linseed oil capsules) in a dosis of 3600 mg each 24 hrs (2 capsules of 2400 mg with the first meal and 1200 mg or 1 capsule with the second meal) during 12 weeks.<br>* Other names: Linseed oil;|
| Placebo Comparator: Placebo of Metformin<br>Active comparator with ACL/Leucine + Placebo of Metformin in individuals with METS | Dietary Supplement: Conjugated linoleic acid/Leucine<br>* Conjugated linoleic acid/Leucine capsules, 825mg time daily with the first bite of eat meal during 12 weeks.<br>* Other names: UKN;Other: Placebo of Metformin<br>* homologate placebo of metformin (calcinated magnesia) in a dosis of 500 mg per day (with the first bite of the second meal) during 8 weeks<br>* Other names: Calcinated magnesia;|
| Placebo Comparator: ACL/Leu placebo<br>Placebo comparator with ACL/Leu placebo + Metformin placebo in individuals with METS | Dietary Supplement: Placebo of ACL/Leucine<br>* Homologate placebo of ACL/Leucine (linseed oil capsules) in a dosis of 3600 mg each 24 hrs (2 capsules of 2400 mg with the first meal and 1200 mg or 1 capsule with the second meal) during 12 weeks.<br>* Other names: Linseed oil;Other: Placebo of Metformin<br>* homologate placebo of metformin (calcinated magnesia) in a dosis of 500 mg per day (with the first bite of the second meal) during 8 weeks<br>* Other names: Calcinated magnesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in visceral fat area messure in centimers ^2 at 8 weeks | Before and after intervention using a visceral fat monitor Omron's dual impedance analysis method scan HDS-2000 | baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2. Change from Baseline epicardial fat area messure in milimeters ^2 at 8 weeks | Before and after intervention with ecocardiogragh imagic master of Kontron Medical. | baseline and 8 weeks | 
| 1. Change from Baseline in weight expressed in kg at 8 weeks | Before and after intervention using a tetrapolar bioelectrical impedance analyzer (body composition analyzer TBF-215 - Tanita) | baseline and 8 weeks | 
| Change from baseline in Body Mass Index, expressed in kg/m^2 at 8 weeks | before and after intervention using a tetrapolar bioelectrical impedance analyzer (body composition analyzer TBF-215 - Tanita) | baseline and 8 weeks | 
| Change from baseline in Total Tody Fat, expressed in percentage at 8 weeks | before and after intervention using a tetrapolar bioelectrical impedance analyzer (body composition analyzer TBF-215 - Tanita) | baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conjugated Linoleic Acid, Leucine, visceral fat area, Epicardial Fat, Hemodinamic Parameters