Metabolic Syndrome X
Conditions
Keywords
Metabolic Syndrome, Central Obesity, Insulin Sensitivity, Ursolic Acid, Triterpenoid
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.
Interventions
DRUGUrsolic acid
Ursolic acid capsules of 150 mg extracted from rosemary, once a day before breakfast
DRUGPlacebo
Calcined magnesia capsules of 150 mg, once a day before breakfast
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Week 12 | The systolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12 |
| Diastolic Blood Pressure | Week 12 | The diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12 |
| Total Insulin Sensitivity | Week 12 | The insulin sensitivity was calculated at baseline and at week 12. The value reported corresponds at week 12 with Matsuda index. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. The entered values reflect the insulin sensitivity |
| Waist Circumference | Week 12 | Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflect the waist circumference measure at week 12 |
| Fasting Glucose | Week 12 | The fasting glucose levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12 |
| Triglycerides | Week 12 | The triglycerides were evaluated at baseline and week 12 with enzymatic-colorimetric techniques and the entered values reflect the triglycerides level at week 12 |
| High Density Lipoprotein Cholesterol (HDL-c) | Week 12 | The HDL-c levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index | Week 12 | The Body Mass index was calculated at baseline and at week 12 with the Quetelet index and the entered values reflect the body mass index at week 12 |
| Total Cholesterol | Week 12 | The total cholesterol was estimated by standardized techniques at baseline and week 12 and the entered values reflect the total cholesterol level at week 12 |
| Low Density Lipoproteins Cholesterol (LDL-c) | Week 12 | The LDL-c levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the c-LDL levels at week 12 |
| Creatinine | Week 12 | The creatinine levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the creatinine levels at week 12 |
| Uric Acid | Week 12 | The uric acid levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the uric acid levels at week 12 |
| Body Weight | Week 12 | The body weight was measured at baseline and week 12 with a bioimpedance balance and the entered values reflect the weight at week 12 |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ursolic Acid Ursolic acid capsules, 150 mg, once a day before breakfast during 12 weeks
Ursolic acid: Ursolic acid capsules of 150 mg extracted from rosemary, once a day before breakfast | 12 |
| Placebo Calcined magnesia capsules, 150 mg, once a day before breakfast during 12 weeks
Placebo: Calcined magnesia capsules of 150 mg, once a day before breakfast | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | Ursolic Acid | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Continuous | 46.5 years STANDARD_DEVIATION 8.7 | 43.7 years STANDARD_DEVIATION 8.5 | 45.1 years STANDARD_DEVIATION 8.6 |
| Body Mass Index | 31.7 kg/m^2 STANDARD_DEVIATION 4.2 | 29.9 kg/m^2 STANDARD_DEVIATION 3.6 | 30.8 kg/m^2 STANDARD_DEVIATION 3.9 |
| Body Weight | 81.5 kg STANDARD_DEVIATION 14 | 75.7 kg STANDARD_DEVIATION 11.5 | 78.6 kg STANDARD_DEVIATION 12.8 |
| Creatinine | 68.1 µmol/L STANDARD_DEVIATION 15 | 61.1 µmol/L STANDARD_DEVIATION 18.6 | 64.6 µmol/L STANDARD_DEVIATION 16.8 |
| Diastolic Blood Pressure | 80 mmHg STANDARD_DEVIATION 10 | 77 mmHg STANDARD_DEVIATION 12 | 78 mmHg STANDARD_DEVIATION 11 |
| Fasting Glucose | 5.8 mmol/L STANDARD_DEVIATION 0.9 | 6.0 mmol/L STANDARD_DEVIATION 0.5 | 5.9 mmol/L STANDARD_DEVIATION 0.7 |
| High Density Lipoprotein cholesterol (HDL-c) | 1.8 mmol/L STANDARD_DEVIATION 0.7 | 1.6 mmol/L STANDARD_DEVIATION 0.6 | 1.7 mmol/L STANDARD_DEVIATION 0.7 |
| Low Density Lipoproteins cholesterol (LDL-c) | 3.5 mmol/L STANDARD_DEVIATION 2.1 | 3.7 mmol/L STANDARD_DEVIATION 1.1 | 3.6 mmol/L STANDARD_DEVIATION 1.6 |
| Region of Enrollment Mexico | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Systolic Blood Pressure | 128 mmHg STANDARD_DEVIATION 20 | 125 mmHg STANDARD_DEVIATION 13 | 127 mmHg STANDARD_DEVIATION 17 |
| Total Cholesterol | 6.0 mmol/L STANDARD_DEVIATION 2 | 6.0 mmol/L STANDARD_DEVIATION 1.4 | 6.0 mmol/L STANDARD_DEVIATION 1.7 |
| Total Insulin Sensitivity | 3.1 index STANDARD_DEVIATION 0.6 | 3.1 index STANDARD_DEVIATION 1.1 | 3.1 index STANDARD_DEVIATION 0.8 |
| Triglycerides | 2.5 mmol/L STANDARD_DEVIATION 0.1 | 2.0 mmol/L STANDARD_DEVIATION 0.6 | 2.3 mmol/L STANDARD_DEVIATION 0.4 |
| Uric acid | 291.5 µmol/L STANDARD_DEVIATION 71.4 | 243.9 µmol/L STANDARD_DEVIATION 53.5 | 267.7 µmol/L STANDARD_DEVIATION 62.5 |
| Waist Circumference | 97 cm STANDARD_DEVIATION 10 | 93 cm STANDARD_DEVIATION 9 | 95 cm STANDARD_DEVIATION 10 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Diastolic Blood Pressure
The diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Diastolic Blood Pressure | 76 mmHg | Standard Deviation 6 |
| Placebo | Diastolic Blood Pressure | 76 mmHg | Standard Deviation 7 |
p-value: 0.373Wilcoxon (Mann-Whitney)
Primary
Fasting Glucose
The fasting glucose levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Fasting Glucose | 4.7 mmol/L | Standard Deviation 0.4 |
| Placebo | Fasting Glucose | 5.7 mmol/L | Standard Deviation 0.7 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Primary
High Density Lipoprotein Cholesterol (HDL-c)
The HDL-c levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | High Density Lipoprotein Cholesterol (HDL-c) | 1.8 mmol/L | Standard Deviation 0.9 |
| Placebo | High Density Lipoprotein Cholesterol (HDL-c) | 1.8 mmol/L | Standard Deviation 0.7 |
p-value: 0.575Wilcoxon (Mann-Whitney)
Primary
Systolic Blood Pressure
The systolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Systolic Blood Pressure | 120 mmHg | Standard Deviation 8 |
| Placebo | Systolic Blood Pressure | 124 mmHg | Standard Deviation 15 |
p-value: 0.169Wilcoxon (Mann-Whitney)
Primary
Total Insulin Sensitivity
The insulin sensitivity was calculated at baseline and at week 12. The value reported corresponds at week 12 with Matsuda index. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. The entered values reflect the insulin sensitivity
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Total Insulin Sensitivity | 4.2 index | Standard Deviation 1.2 |
| Placebo | Total Insulin Sensitivity | 2.6 index | Standard Deviation 1.4 |
p-value: 0.003Wilcoxon (Mann-Whitney)
Primary
Triglycerides
The triglycerides were evaluated at baseline and week 12 with enzymatic-colorimetric techniques and the entered values reflect the triglycerides level at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Triglycerides | 1.8 mmol/L | Standard Deviation 0.8 |
| Placebo | Triglycerides | 2.5 mmol/L | Standard Deviation 1.3 |
p-value: 0.308Wilcoxon (Mann-Whitney)
Primary
Waist Circumference
Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflect the waist circumference measure at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Waist Circumference | 83 cm | Standard Deviation 9 |
| Placebo | Waist Circumference | 96 cm | Standard Deviation 8 |
p-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
Body Mass Index
The Body Mass index was calculated at baseline and at week 12 with the Quetelet index and the entered values reflect the body mass index at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Body Mass Index | 24.9 kg/m^2 | Standard Deviation 1.2 |
| Placebo | Body Mass Index | 32.1 kg/m^2 | Standard Deviation 3.9 |
p-value: 0.049Wilcoxon (Mann-Whitney)
Secondary
Body Weight
The body weight was measured at baseline and week 12 with a bioimpedance balance and the entered values reflect the weight at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Body Weight | 71 kg | Standard Deviation 11 |
| Placebo | Body Weight | 81 kg | Standard Deviation 15 |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Creatinine
The creatinine levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the creatinine levels at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Creatinine | 0.06 mmol/L | Standard Deviation 0.02 |
| Placebo | Creatinine | 0.06 mmol/L | Standard Deviation 0.02 |
p-value: 0.953Wilcoxon (Mann-Whitney)
Secondary
Low Density Lipoproteins Cholesterol (LDL-c)
The LDL-c levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the c-LDL levels at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Low Density Lipoproteins Cholesterol (LDL-c) | 2.8 mmol/L | Standard Deviation 1.2 |
| Placebo | Low Density Lipoproteins Cholesterol (LDL-c) | 4.3 mmol/L | Standard Deviation 2.3 |
p-value: 0.116Wilcoxon (Mann-Whitney)
Secondary
Total Cholesterol
The total cholesterol was estimated by standardized techniques at baseline and week 12 and the entered values reflect the total cholesterol level at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Total Cholesterol | 5.2 mmol/L | Standard Deviation 1.2 |
| Placebo | Total Cholesterol | 6.4 mmol/L | Standard Deviation 1.9 |
p-value: 0.224Wilcoxon (Mann-Whitney)
Secondary
Uric Acid
The uric acid levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the uric acid levels at week 12
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ursolic Acid | Uric Acid | 249.8 µmol/L | Standard Deviation 53.5 |
| Placebo | Uric Acid | 422.3 µmol/L | Standard Deviation 124.9 |
p-value: 0.999Wilcoxon (Mann-Whitney)