Bezafibrate Plus Berberine in Mixed Dyslipidemia

Effect of Berberine Plus Bezafibrate Administration on the Lipid Profile of Patients With Mixed Dyslipidemia: A Pilot Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Mixed Dyslipidemia
• Intervention / Treatment: Drug: Berberine; Drug: Bezafibrate; Drug: Berberine plus Bezafibrate

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Esperanza Martínez-Abundis, PhD; Phone Number: 34211 (33) 1058-5200; Email: esperanzamartnezabundi@yahoo.com

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Berberine; Berberine 500 mg with breakfast, meal, and dinner.	Drug: Berberine; 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.
Experimental: Bezafibrate; Bezafibrate 200 mg on breakfast and dinner.	Drug: Bezafibrate; Bezafibrate capsule 400 mg each 24 h for 90 days. 1 Bezafibrate capsule 200 mg for breakfast. 1 Bezafibrate capsule 200 mg for dinner.
Experimental: Berberine plus Bezafibrate; Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.	Drug: Berberine 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.; Other Names: Berberine, bezafibrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	90 days
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.	90 days
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.	90 days
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.	90 days
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.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	90 days
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.	90 days
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.	90 days
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.	90 days
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.	90 days
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.	90 days
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.	90 days
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.	90 days

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: Esperanza Martínez-Abundis, INTEC, CUCS, University of Guadalajara

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: September 10, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Berberine; Bezafibrate
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Bezafibrate
• Other Study ID Numbers: EABYBL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No