Mixed Dyslipidemia
Conditions
Keywords
Berberine, Bezafibrate
Brief summary
Dyslipidemia, is a cardiovascular risk factor of great importance whose prevalence has increased over the last decade. Part of the components of metabolic syndrome and consensus so far contemplated to increased triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) as part of the elements for classification, which includes mixed dyslipidemia. Currently, fibrates, such as bezafibrate, are drugs used in treating hypertriglyceridemia, besides reducing the risk of coronary disease. However, although this treatment is safe, it is not without risks; with increased prevalence of adverse effects as the dose thereof is increased or joins combination with a statin drug for the treatment of mixed dyslipidemia long term. Among the alternative therapies is berberine, which to reduce cholesterol and triglycerides may be useful in combination with bezafibrate in the treatment of mixed dyslipidemia and as an option with lower cost and lower frequency of adverse events.
Detailed description
The aim of this study is to evaluate the effect of berberine plus bezafibrate administration on the lipid profile of patients with mixed dyslipidemia.The investigators will conduct a double-blind randomized pilot clinical trial with parallel groups in men and women aged 30-60 years old with diagnosis of mixed dyslipidemia. Patients will be assigned to 3 groups: 1. 12 patients will receive berberine, 1500 mg / day 2. 12 Patients will receive bezafibrate 400 mg / day 3. 12 patients will receive a combination of berberine (1500 mg / day) plus bezafibrate (400 mg / day). All participants will be determined before and after the intervention: lipid profile, total cholesterol (TC), triglycerides (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL). Also weight, Body Mass Index (BMI), waist circumference (WC), glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatinine (CR) uric acid (UA) and tolerability. Statistical analysis was performed upon the sample of subjects. Previous start the statistical analysis of the groups will proceed to verify the behavior of the distribution of the variables included by Z Kolmogorov-Smirnov goodness of fit. The distribution of all the variables under this test is cataloged in normal or not normal, which define the type of statistical test would be performed (parametric or non-parametric). However, based on the sample size, non-parametric tests will be those considered most suitable for application. The data obtained will be expressed and presented using measures of central tendency and dispersion for quantitative (mean and standard deviation) variables and qualitative variables are expressed as frequencies and percentages.
Interventions
DRUGBerberine
Berberine 1500 mg, each 24 h for 90 days 1 Berberine capsule 500 mg for breakfast. 1 Berberine capsule 500 mg for lunch. 1 Berberine capsule 500 mg for dinner.
DRUGBezafibrate
Bezafibrate capsule 400 mg each 24 h for 90 days. 1 Bezafibrate capsule 200 mg for breakfast. 1 Bezafibrate capsule 200 mg for dinner.
DRUGBerberine plus Bezafibrate
Berberine 1500 mg each 24 h for 90 days 1 Berberine capsule 500 mg for breakfast. 1 Berberine capsule 500 mg for lunch. 1 Berberine capsule 500 mg for dinner. Bezafibrate 400 mg each 24 h for 90 days. 1 Bezafibrate capsule 200 mg for breakfast. 1 Bezafibrate capsule 200 mg for dinner.
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Someone of the team make a key number for each patient (36 enrolled, 12 for each intervention), and then put the numbers in to 36 paper envelopes and let the patient chose one. There was double-blind. And the placebo was calcined magnesia.
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
A. Men and women B. Accomplished age 30 to 60 years C. Diagnosis of mixed dyslipidemia established to meet the following criteria: * Total cholesterol \> 5,17 mmol/l. * Triglycerides \> 1,7 mmol/l. D. BMI of 25 kg / m\^2 to 39.9 kg / m\^2, weight stable over the past three months, defined as a variability in the lower body weight of 5%. E. No drug treatment for lipid profile 3 months prior to baseline. F. Women must ensure a non-hormonal method to avoid pregnancy during the study period. G. Written information consent
Exclusion criteria
A. Removal for informed consent letter B. Loss of monitoring C. Presence of serious adverse event D. Adherence to treatment \<80% E. Consumption of drugs known about lipid profile, glucose metabolism, blood pressure and body weight during the intervention period influence F. Intolerance or not tolerability or hypersensitivity to the compounds used in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Triglycerides After 90 Days | 90 days | The blood sample for the determination of triglycerides was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| Total Cholesterol After 90 Days. | 90 days | The blood sample for the determination of total cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days | 90 days | The blood sample for the determination of low density lipoprotein cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| High Density Lipoprotein Cholesterol (HDL-c) After 90 Days | 90 days | The blood sample for the determination of high density lipoprotein cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| Very Low Density Lipoprotein After 90 Days | 90 days | The blood sample for the determination of VLDL was taken after an overnight fast and was calculated at baseline and after 90 days as triglycerides/5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Serum Glucose (FSG) After 90 Days | 90 days | The glucose oxidase technique (Beckman Instruments, Inc., Brea, California, USA) was used to determine fasting serum glucose at baseline and after 90 days with an intra- and interassay coefficient of variation of \<1. |
| Body Weight (BW) After 90 Days | 90 days | The body weight was evaluated at baseline and after 90 days after an overnight fast, through a bioimpedance digital scale results are reported in kilograms with a decimal. |
| Creatinine After 90 Days | 90 days | The blood sample for the determination of creatinine was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| Uric Acid After 90 Days | 90 days | The blood sample for the determination of uric acid was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method. |
| Body Mass Index (BMI) After 90 Days | 90 days | The BMI was calculated at baseline and after 90 days by the square of the body height, and is universally expressed in units of kg/m\^2, resulting from mass in kilograms and height in metres. |
| Waist Circumference (WC) After 90 Days | 90 days | The waist circumference was evaluated at baseline and after 90 days after an overnight fast with a flexible tape in the midpoint between the lowest rib and the iliac crest and is expressed in centimeters. |
| Systolic Blood Pressure After 90 Days | 90 days | The systolic blood pressure was evaluated at baseline and after 90 days with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of SBP. The value was expressed on mmHg. |
| Diastolic Blood Pressure After 90 Days | 90 days | The diastolic blood pressure was evaluated at baseline and after 90 days with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of DBP. The value was expressed on mmHg. |
Countries
Mexico
Participant flow
Pre-assignment details
A total of 60 subjects were screened. After a selection process and the signature of the consenting letter, 36 patients were included in the study 12 men and 24 women, they were randomized in one of the 3 groups
Participants by arm
| Arm | Count |
|---|---|
| Berberine Berberine, 1500 mg/day | 12 |
| Bezafibrate Bezafibrate, 400 mg/day | 12 |
| Berberine Plus Bezafibrate Berberine (1500 mg/day) plus bezafibrate (400 mg/day) | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Berberine Plus Bezafibrate | Bezafibrate | Berberine |
|---|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 9.3 | 46.8 years STANDARD_DEVIATION 10.5 | 44.8 years STANDARD_DEVIATION 9 | 46.4 years STANDARD_DEVIATION 8.6 |
| Body mass index (BMI) | 30.2 kg/m^2 STANDARD_DEVIATION 3.9 | 29.0 kg/m^2 STANDARD_DEVIATION 3.3 | 31.5 kg/m^2 STANDARD_DEVIATION 4.3 | 30.1 kg/m^2 STANDARD_DEVIATION 4.1 |
| Body weight | 78.5 kg STANDARD_DEVIATION 11 | 74.6 kg STANDARD_DEVIATION 6.5 | 83.3 kg STANDARD_DEVIATION 16.3 | 77.6 kg STANDARD_DEVIATION 10.3 |
| Creatinine (Cr) | 67.76 mmol/L STANDARD_DEVIATION 26.5 | 61.9 mmol/L STANDARD_DEVIATION 26.5 | 70.7 mmol/L STANDARD_DEVIATION 26.5 | 70.7 mmol/L STANDARD_DEVIATION 26.5 |
| Diastolic blood pressure (DBP) | 75.3 mmHg STANDARD_DEVIATION 6.6 | 76 mmHg STANDARD_DEVIATION 6 | 74 mmHg STANDARD_DEVIATION 8 | 76 mmHg STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 12 Participants | 12 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glucose | 5.46 mmol/L STANDARD_DEVIATION 0.63 | 5.5 mmol/L STANDARD_DEVIATION 0.6 | 5.5 mmol/L STANDARD_DEVIATION 0.5 | 5.4 mmol/L STANDARD_DEVIATION 0.8 |
| High-density lipoprotein cholesterol (HDL-C) | 1.7 mmol/L STANDARD_DEVIATION 0.43 | 1.7 mmol/L STANDARD_DEVIATION 0.4 | 1.6 mmol/L STANDARD_DEVIATION 0.5 | 1.8 mmol/L STANDARD_DEVIATION 0.4 |
| Low-density lipoprotein cholesterol (LDL-C) | 3.43 mmol/L STANDARD_DEVIATION 0.73 | 3.4 mmol/L STANDARD_DEVIATION 0.6 | 3.2 mmol/L STANDARD_DEVIATION 0.9 | 3.7 mmol/L STANDARD_DEVIATION 0.7 |
| Region of Enrollment Mexico | 36 participants | 12 participants | 12 participants | 12 participants |
| Sex: Female, Male Female | 24 Participants | 10 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 12 Participants | 2 Participants | 6 Participants | 4 Participants |
| Systolic blood pressure (SBP) | 121 mmHg STANDARD_DEVIATION 10.6 | 118 mmHg STANDARD_DEVIATION 10 | 124 mmHg STANDARD_DEVIATION 11 | 121 mmHg STANDARD_DEVIATION 11 |
| Total cholesterol (TC) | 6.1 mmol/L STANDARD_DEVIATION 0.56 | 6.3 mmol/L STANDARD_DEVIATION 0.7 | 6.0 mmol/L STANDARD_DEVIATION 0.4 | 6.0 mmol/L STANDARD_DEVIATION 0.6 |
| Triglycerides (TG) | 2.43 mmol/L STANDARD_DEVIATION 0.8 | 2.6 mmol/L STANDARD_DEVIATION 0.8 | 2.2 mmol/L STANDARD_DEVIATION 0.8 | 2.5 mmol/L STANDARD_DEVIATION 0.8 |
| Uric Acid (UA) | 328.3 mmol/L STANDARD_DEVIATION 75.3 | 303.3 mmol/L STANDARD_DEVIATION 83.3 | 366.5 mmol/L STANDARD_DEVIATION 59.5 | 315.2 mmol/L STANDARD_DEVIATION 83.3 |
| Very low density lipoprotein (VLDL) | 0.46 mmol/L STANDARD_DEVIATION 0.16 | 0.5 mmol/L STANDARD_DEVIATION 0.2 | 0.4 mmol/L STANDARD_DEVIATION 0.1 | 0.5 mmol/L STANDARD_DEVIATION 0.2 |
| Waist circumference | 95.1 cm STANDARD_DEVIATION 9.9 | 89.7 cm STANDARD_DEVIATION 8.4 | 99.1 cm STANDARD_DEVIATION 11.8 | 95.6 cm STANDARD_DEVIATION 9.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 5 / 12 | 5 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
High Density Lipoprotein Cholesterol (HDL-c) After 90 Days
The blood sample for the determination of high density lipoprotein cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | High Density Lipoprotein Cholesterol (HDL-c) After 90 Days | 1.5 mM | Standard Deviation 0.3 |
| Bezafibrate | High Density Lipoprotein Cholesterol (HDL-c) After 90 Days | 2.0 mM | Standard Deviation 0.3 |
| Berberine Plus Bezafibrate | High Density Lipoprotein Cholesterol (HDL-c) After 90 Days | 1.8 mM | Standard Deviation 0.5 |
Primary
Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days
The blood sample for the determination of low density lipoprotein cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days | 2.8 mM | Standard Deviation 0.8 |
| Bezafibrate | Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days | 2.4 mM | Standard Deviation 0.6 |
| Berberine Plus Bezafibrate | Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days | 2.2 mM | Standard Deviation 1.3 |
Primary
Total Cholesterol After 90 Days.
The blood sample for the determination of total cholesterol was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Total Cholesterol After 90 Days. | 5.3 mM | Standard Deviation 0.5 |
| Bezafibrate | Total Cholesterol After 90 Days. | 5.8 mM | Standard Deviation 0.8 |
| Berberine Plus Bezafibrate | Total Cholesterol After 90 Days. | 4.6 mM | Standard Deviation 1.2 |
Primary
Triglycerides After 90 Days
The blood sample for the determination of triglycerides was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Triglycerides After 90 Days | 2.3 mmol/L | Standard Deviation 0.9 |
| Bezafibrate | Triglycerides After 90 Days | 1.1 mmol/L | Standard Deviation 0.4 |
| Berberine Plus Bezafibrate | Triglycerides After 90 Days | 1.3 mmol/L | Standard Deviation 0.7 |
Primary
Very Low Density Lipoprotein After 90 Days
The blood sample for the determination of VLDL was taken after an overnight fast and was calculated at baseline and after 90 days as triglycerides/5.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Very Low Density Lipoprotein After 90 Days | 0.4 mM | Standard Deviation 0.1 |
| Bezafibrate | Very Low Density Lipoprotein After 90 Days | 0.2 mM | Standard Deviation 0 |
| Berberine Plus Bezafibrate | Very Low Density Lipoprotein After 90 Days | 0.2 mM | Standard Deviation 0.1 |
Secondary
Body Mass Index (BMI) After 90 Days
The BMI was calculated at baseline and after 90 days by the square of the body height, and is universally expressed in units of kg/m\^2, resulting from mass in kilograms and height in metres.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Body Mass Index (BMI) After 90 Days | 29.6 kg/m^2 | Standard Deviation 4.4 |
| Bezafibrate | Body Mass Index (BMI) After 90 Days | 31.8 kg/m^2 | Standard Deviation 3.4 |
| Berberine Plus Bezafibrate | Body Mass Index (BMI) After 90 Days | 28.4 kg/m^2 | Standard Deviation 2.8 |
Secondary
Body Weight (BW) After 90 Days
The body weight was evaluated at baseline and after 90 days after an overnight fast, through a bioimpedance digital scale results are reported in kilograms with a decimal.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Body Weight (BW) After 90 Days | 75.4 kg | Standard Deviation 10.2 |
| Bezafibrate | Body Weight (BW) After 90 Days | 83.6 kg | Standard Deviation 10.7 |
| Berberine Plus Bezafibrate | Body Weight (BW) After 90 Days | 73.0 kg | Standard Deviation 6.2 |
Secondary
Creatinine After 90 Days
The blood sample for the determination of creatinine was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Creatinine After 90 Days | 53.0 mM | Standard Deviation 26.5 |
| Bezafibrate | Creatinine After 90 Days | 44.2 mM | Standard Deviation 35.4 |
| Berberine Plus Bezafibrate | Creatinine After 90 Days | 61.9 mM | Standard Deviation 35.4 |
Secondary
Diastolic Blood Pressure After 90 Days
The diastolic blood pressure was evaluated at baseline and after 90 days with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of DBP. The value was expressed on mmHg.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Diastolic Blood Pressure After 90 Days | 73 mmHg | Standard Deviation 8 |
| Bezafibrate | Diastolic Blood Pressure After 90 Days | 74 mmHg | Standard Deviation 11 |
| Berberine Plus Bezafibrate | Diastolic Blood Pressure After 90 Days | 72 mmHg | Standard Deviation 10 |
Secondary
Fasting Serum Glucose (FSG) After 90 Days
The glucose oxidase technique (Beckman Instruments, Inc., Brea, California, USA) was used to determine fasting serum glucose at baseline and after 90 days with an intra- and interassay coefficient of variation of \<1.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Fasting Serum Glucose (FSG) After 90 Days | 5.6 mM | Standard Deviation 0.4 |
| Bezafibrate | Fasting Serum Glucose (FSG) After 90 Days | 5.5 mM | Standard Deviation 0.5 |
| Berberine Plus Bezafibrate | Fasting Serum Glucose (FSG) After 90 Days | 5.3 mM | Standard Deviation 0.3 |
Secondary
Systolic Blood Pressure After 90 Days
The systolic blood pressure was evaluated at baseline and after 90 days with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of SBP. The value was expressed on mmHg.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Systolic Blood Pressure After 90 Days | 122 mmHg | Standard Deviation 10 |
| Bezafibrate | Systolic Blood Pressure After 90 Days | 122 mmHg | Standard Deviation 13 |
| Berberine Plus Bezafibrate | Systolic Blood Pressure After 90 Days | 114 mmHg | Standard Deviation 10 |
Secondary
Uric Acid After 90 Days
The blood sample for the determination of uric acid was taken after an overnight fast and was evaluated at baseline and after 90 days by spectrophotometry method.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Uric Acid After 90 Days | 285.5 mM | Standard Deviation 166.5 |
| Bezafibrate | Uric Acid After 90 Days | 350.9 mM | Standard Deviation 53.5 |
| Berberine Plus Bezafibrate | Uric Acid After 90 Days | 279.5 mM | Standard Deviation 89.2 |
Secondary
Waist Circumference (WC) After 90 Days
The waist circumference was evaluated at baseline and after 90 days after an overnight fast with a flexible tape in the midpoint between the lowest rib and the iliac crest and is expressed in centimeters.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine | Waist Circumference (WC) After 90 Days | 94.0 cm | Standard Deviation 11.2 |
| Bezafibrate | Waist Circumference (WC) After 90 Days | 98.0 cm | Standard Deviation 12 |
| Berberine Plus Bezafibrate | Waist Circumference (WC) After 90 Days | 88.7 cm | Standard Deviation 9.2 |