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

Phase 2

Completed

• Conditions: Metabolic Syndrome
• Interventions: Dietary Supplement: Conjugated linoleic acid/Leucine; Dietary Supplement: Placebo of ACL/Leucine; Other: Placebo of Metformin; Drug: Metformin

• Registration Number: NCT02629627
• Lead Sponsor: Centro Universitario de Ciencias de la Salud, Mexico

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-12-10
• Study First Submitted QC: 2015-12-10
• Study First Posted: 2015-12-14
• Study Start: 2016-03
• Primary Completion: 2017-03
• Study Completion: 2017-10
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-01
• Last Update Posted: 2018-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo of Metformin	Conjugated linoleic acid/Leucine	Active comparator with ACL/Leucine + Placebo of Metformin in individuals with METS
ACL/Leu placebo	Placebo of ACL/Leucine	Placebo comparator with ACL/Leu placebo + Metformin placebo in individuals with METS
Metformin+placebo conjugatedALC/leucine	Placebo of ACL/Leucine	active comparator with Metformin 500mg + Placebo of ACL/Leucine in individuals with METS
Placebo of Metformin	Placebo of Metformin	Active comparator with ACL/Leucine + Placebo of Metformin in individuals with METS
ACL/Leu placebo	Placebo of Metformin	Placebo comparator with ACL/Leu placebo + Metformin placebo in individuals with METS
cojugated ALC/Leucine+Metformin	Conjugated linoleic acid/Leucine	Intervention with conjugated linoleic acid/Leucine + 500mg in individuals with METS
cojugated ALC/Leucine+Metformin	Metformin	Intervention with conjugated linoleic acid/Leucine + 500mg in individuals with METS
Metformin+placebo conjugatedALC/leucine	Metformin	active comparator with Metformin 500mg + Placebo of ACL/Leucine in individuals with METS

Primary Outcome Measures

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

Secondary Outcome Measures

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