Clinical trial NCT02337933: Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome
Official title: Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolic Syndrome X
Keywords: Metabolic Syndrome
Central Obesity
Insulin Sensitivity
Ursolic Acid
Triterpenoid
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The metabolic syndrome is characterized by the presence of overweight/obesity, insulin resistance, hyperglycemia, dyslipidaemia and hypertension and an inflammatory state, which together increase the risk of developing cardiovascular disease (CVD) or diabetes mellitus type 2 (DM2). It is also characterized by a decreased insulin sensitivity, namely, lower ability of insulin to metabolize glucose, key in the physiopathogeny of disease process.

In the search for a pharmacological agent that can attend more components of the metabolic syndrome and above all improve insulin sensitivity to effectively prevent the development of CVD and DM2, ursolic acid is a promising compound.

Ursolic acid is a pentacyclic carboxylic acid present in medicinal herbs, parts of some fruits like apple peel, and plants such as rosemary. There is scientific evidence of important benefits of ursolic acid level in vitro and in vivo on insulin, metabolism of lipids and glucose, as well as on the body weight and metabolic parameters. However, the results are not clear and the mechanisms are not fully elucidate.

The aim of this study is to evaluate the effect of ursolic acid on the insulin sensitivity and metabolic syndrome.

Detailed description: A randomized, double-blind, placebo-controlled clinical trial in 24 patients of both sexes aged between 30 and 60 years, with a diagnosis of metabolic syndrome according to the modified International Diabetes Federation (IDF) criteria, without treatment.

They will be assigned randomly two groups of 12 patients, each to receive 150 mg of ursolic acid or placebo before breakfast for 12 weeks.

Insulin sensitivity will be calculated by Matsuda Index with dates from glucose and insulin levels from Oral Glucose Tolerance Test; Waist circumference will be measured; triglycerides and High density lipoprotein (HDL-C) and blood pressure will be evaluated before and after intervention in both groups.

Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. Will be considered statistical significance p ≤0.05.

This protocol was approved by a local ethics committee (CEI/075/2014) and written informed consent will be obtained from all volunteers.

Eligibility criteria: Inclusion Criteria:

* Informed consent signed
* Patients both sexes
* Age between 30 and 60 years
* Metabolic Syndrome according to the IDF criteria:
* Waist circumference Man ≥90 cm, Woman ≥80 cm; and two of the following criteria:
* High density lipoprotein Man ≤40 mg/dL, Woman ≤50 mg/dL;
* Fasting glucose ≥100 mg/dL;
* Triglycerides ≥150 mg/dL;
* Blood pressure ≥130/85 mmHg

Exclusion Criteria:

* Women with confirmed or suspected pregnancy
* Women under lactation and/or puerperium
* Hypersensibility to ursolic acid o calcined magnesia
* Physical impossibility for taking pills
* Known uncontrolled renal, hepatic, heart or thyroid diseased
* Previous treatment for the metabolic syndrome components
* Body Mass Index ≥39.9 kg/m2
* Fasting glucose ≥126 mg/dL
* Triglycerides ≥500 mg/dL
* Total cholesterol ≥240 mg/dL
* Low density lipoprotein (c-LDL) ≥190 mg/dL
* Blood Pressure ≥140/90 mmHg

Primary outcomes:
measure: Total Insulin Sensitivity
timeFrame: Week 12
measure: Waist Circumference
timeFrame: Week 12
measure: Fasting Glucose
timeFrame: Week 12
measure: Triglycerides
timeFrame: Week 12
measure: High Density Lipoprotein Cholesterol (HDL-c)
timeFrame: Week 12
measure: Systolic Blood Pressure
timeFrame: Week 12
measure: Diastolic Blood Pressure
timeFrame: Week 12
Secondary outcomes:
measure: Body Weight
timeFrame: Week 12
measure: Body Mass Index
timeFrame: Week 12
measure: Total Cholesterol
timeFrame: Week 12
measure: Low Density Lipoproteins Cholesterol (LDL-c)
timeFrame: Week 12
measure: Creatinine
timeFrame: Week 12
measure: Uric Acid
timeFrame: Week 12
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Instituto de Terapéutica Experimental y Clínica
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: Manuel González-Ortíz, PhD
role: PRINCIPAL_INVESTIGATOR
References: