Clinical trial NCT02629627: Conjugated Linoleic Acid / Leucine Versus Metformin on Visceral Fat in Metabolic Syndrome
Official title: Effect of the Administration of Conjugated Linoleic Acid / Leucine Plus Metformin on Visceral Fat in Patients With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolic Syndrome
Keywords: Conjugated Linoleic Acid
Leucine
visceral fat area
Epicardial Fat
Hemodinamic Parameters
Lead sponsor: Centro Universitario de Ciencias de la Salud, Mexico
Sponsor class: OTHER
First posted: 2015-12-14
Enrollment: 104
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in visceral fat area messure in centimers ^2 at 8 weeks
timeFrame: baseline and 8 weeks
Secondary outcomes:
measure: 2. Change from Baseline epicardial fat area messure in milimeters ^2 at 8 weeks
timeFrame: baseline and 8 weeks
measure: 1. Change from Baseline in weight expressed in kg at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from baseline in Body Mass Index, expressed in kg/m^2 at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from baseline in Total Tody Fat, expressed in percentage at 8 weeks
timeFrame: baseline and 8 weeks
Other outcomes:
measure: Change from Baseline in central systolic blood pressure in mm/Hg at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Pulse Wave Velocity in meters/ second at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Fasting plasma glucose in mg/dL at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Total cholesterol in mg/dL at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Triglycerids in mg/dL at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in High-density lipoprotein colesterol in mg/dL at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Low-density lipoprotein colesterol in mg/dL at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Alanine aminotransferase in IU/L at 8 weeks
timeFrame: baseline and 8 weeks
measure: Change from Baseline in Aspartate aminotransferase in UI/L at 8 weeks
timeFrame: baseline and 8 weeks
Locations:
Study officials:
affiliation: Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara
name: Fernando Grover-Páez, PhD
role: PRINCIPAL_INVESTIGATOR
References: