Trial Outcomes & Findings for Bezafibrate Plus Berberine in Mixed Dyslipidemia (NCT NCT02548832)

NCT ID: NCT02548832

Last Updated: 2023-02-24

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 36 participants
• Primary outcome timeframe: 90 days
• Results posted on: 2023-02-24

Participant Flow

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

Participant milestones

Measure	Berberine Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Berberine 500 mg with breakfast, meal, and dinner, and placebo only on breakfast and dinner Berberine Hydrochloride 500 mg oral capsule: Berberine 1500 mg., homologated with placebo each 24 h for 90 days 1 berberine capsule 500 mg for breakfast and 1 of placebo. 1 berberine capsule 500 mg for lunch. 1 berberine capsule 500 mg and 1 placebo for dinner. Homologated with placebo 1 for breakfast and 1 for dinner.	Bezafibrate Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Placebo 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner. Bezafibrate 200 mg oral capsule: Bezafibrate capsule 400 mg each 24 h for 90 days. 1 bezafibrate 200 mg for breakfast. 1 of bezafibrate 200 mg for dinner. Homologated with placebo 1 for breakfast, 1 for lunch and 1 for dinner.	Berberine Plus Bezafibrate Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner. Berberine Hydrochloride 500 mg and Bezafibrate 200 mg oral capsules: Berberine hydrochloride capsule 500 and bezafibrate capsule 200 mg each 24 h for 90 days. 1 berberine and 1 of bezafibrate 200 mg for breakfast 1 berberine for lunch 1 berberine and 1 of bezafibrate 200 mg for dinner
Overall Study STARTED	12	12	12
Overall Study COMPLETED	10	10	10
Overall Study NOT COMPLETED	2	2	2

Reasons for withdrawal

Measure	Berberine Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Berberine 500 mg with breakfast, meal, and dinner, and placebo only on breakfast and dinner Berberine Hydrochloride 500 mg oral capsule: Berberine 1500 mg., homologated with placebo each 24 h for 90 days 1 berberine capsule 500 mg for breakfast and 1 of placebo. 1 berberine capsule 500 mg for lunch. 1 berberine capsule 500 mg and 1 placebo for dinner. Homologated with placebo 1 for breakfast and 1 for dinner.	Bezafibrate Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Placebo 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner. Bezafibrate 200 mg oral capsule: Bezafibrate capsule 400 mg each 24 h for 90 days. 1 bezafibrate 200 mg for breakfast. 1 of bezafibrate 200 mg for dinner. Homologated with placebo 1 for breakfast, 1 for lunch and 1 for dinner.	Berberine Plus Bezafibrate Men and women aged 30 to 60 years with established diagnosis of mixed dyslipidemia: Total Cholesterol \> 5,17 mmol/L, Triglycerides \> 1,7 mmol/L. Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner. Berberine Hydrochloride 500 mg and Bezafibrate 200 mg oral capsules: Berberine hydrochloride capsule 500 and bezafibrate capsule 200 mg each 24 h for 90 days. 1 berberine and 1 of bezafibrate 200 mg for breakfast 1 berberine for lunch 1 berberine and 1 of bezafibrate 200 mg for dinner
Overall Study Lost to Follow-up	2	2	2

Baseline Characteristics

Bezafibrate Plus Berberine in Mixed Dyslipidemia

Baseline characteristics by cohort

Measure	Berberine n=12 Participants Berberine, 1500 mg/day	Bezafibrate n=12 Participants Bezafibrate, 400 mg/day	Berberine Plus Bezafibrate n=12 Participants Berberine (1500 mg/day) plus bezafibrate (400 mg/day)	Total n=36 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 8.6 • n=5 Participants	44.8 years STANDARD_DEVIATION 9 • n=7 Participants	46.8 years STANDARD_DEVIATION 10.5 • n=5 Participants	46 years STANDARD_DEVIATION 9.3 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	36 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Mexico	12 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	36 participants n=4 Participants
Triglycerides (TG)	2.5 mmol/L STANDARD_DEVIATION 0.8 • n=5 Participants	2.2 mmol/L STANDARD_DEVIATION 0.8 • n=7 Participants	2.6 mmol/L STANDARD_DEVIATION 0.8 • n=5 Participants	2.43 mmol/L STANDARD_DEVIATION 0.8 • n=4 Participants
Low-density lipoprotein cholesterol (LDL-C)	3.7 mmol/L STANDARD_DEVIATION 0.7 • n=5 Participants	3.2 mmol/L STANDARD_DEVIATION 0.9 • n=7 Participants	3.4 mmol/L STANDARD_DEVIATION 0.6 • n=5 Participants	3.43 mmol/L STANDARD_DEVIATION 0.73 • n=4 Participants
Total cholesterol (TC)	6.0 mmol/L STANDARD_DEVIATION 0.6 • n=5 Participants	6.0 mmol/L STANDARD_DEVIATION 0.4 • n=7 Participants	6.3 mmol/L STANDARD_DEVIATION 0.7 • n=5 Participants	6.1 mmol/L STANDARD_DEVIATION 0.56 • n=4 Participants
High-density lipoprotein cholesterol (HDL-C)	1.8 mmol/L STANDARD_DEVIATION 0.4 • n=5 Participants	1.6 mmol/L STANDARD_DEVIATION 0.5 • n=7 Participants	1.7 mmol/L STANDARD_DEVIATION 0.4 • n=5 Participants	1.7 mmol/L STANDARD_DEVIATION 0.43 • n=4 Participants
Very low density lipoprotein (VLDL)	0.5 mmol/L STANDARD_DEVIATION 0.2 • n=5 Participants	0.4 mmol/L STANDARD_DEVIATION 0.1 • n=7 Participants	0.5 mmol/L STANDARD_DEVIATION 0.2 • n=5 Participants	0.46 mmol/L STANDARD_DEVIATION 0.16 • n=4 Participants
Glucose	5.4 mmol/L STANDARD_DEVIATION 0.8 • n=5 Participants	5.5 mmol/L STANDARD_DEVIATION 0.5 • n=7 Participants	5.5 mmol/L STANDARD_DEVIATION 0.6 • n=5 Participants	5.46 mmol/L STANDARD_DEVIATION 0.63 • n=4 Participants
Uric Acid (UA)	315.2 mmol/L STANDARD_DEVIATION 83.3 • n=5 Participants	366.5 mmol/L STANDARD_DEVIATION 59.5 • n=7 Participants	303.3 mmol/L STANDARD_DEVIATION 83.3 • n=5 Participants	328.3 mmol/L STANDARD_DEVIATION 75.3 • n=4 Participants
Creatinine (Cr)	70.7 mmol/L STANDARD_DEVIATION 26.5 • n=5 Participants	70.7 mmol/L STANDARD_DEVIATION 26.5 • n=7 Participants	61.9 mmol/L STANDARD_DEVIATION 26.5 • n=5 Participants	67.76 mmol/L STANDARD_DEVIATION 26.5 • n=4 Participants
Body mass index (BMI)	30.1 kg/m^2 STANDARD_DEVIATION 4.1 • n=5 Participants	31.5 kg/m^2 STANDARD_DEVIATION 4.3 • n=7 Participants	29.0 kg/m^2 STANDARD_DEVIATION 3.3 • n=5 Participants	30.2 kg/m^2 STANDARD_DEVIATION 3.9 • n=4 Participants
Waist circumference	95.6 cm STANDARD_DEVIATION 9.6 • n=5 Participants	99.1 cm STANDARD_DEVIATION 11.8 • n=7 Participants	89.7 cm STANDARD_DEVIATION 8.4 • n=5 Participants	95.1 cm STANDARD_DEVIATION 9.9 • n=4 Participants
Body weight	77.6 kg STANDARD_DEVIATION 10.3 • n=5 Participants	83.3 kg STANDARD_DEVIATION 16.3 • n=7 Participants	74.6 kg STANDARD_DEVIATION 6.5 • n=5 Participants	78.5 kg STANDARD_DEVIATION 11.0 • n=4 Participants
Systolic blood pressure (SBP)	121 mmHg STANDARD_DEVIATION 11 • n=5 Participants	124 mmHg STANDARD_DEVIATION 11 • n=7 Participants	118 mmHg STANDARD_DEVIATION 10 • n=5 Participants	121 mmHg STANDARD_DEVIATION 10.6 • n=4 Participants
Diastolic blood pressure (DBP)	76 mmHg STANDARD_DEVIATION 6 • n=5 Participants	74 mmHg STANDARD_DEVIATION 8 • n=7 Participants	76 mmHg STANDARD_DEVIATION 6 • n=5 Participants	75.3 mmHg STANDARD_DEVIATION 6.6 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Triglycerides After 90 Days	2.3 mmol/L Standard Deviation 0.9	1.1 mmol/L Standard Deviation 0.4	1.3 mmol/L Standard Deviation 0.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Total Cholesterol After 90 Days.	5.3 mM Standard Deviation 0.5	5.8 mM Standard Deviation 0.8	4.6 mM Standard Deviation 1.2

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Low Density Lipoprotein Cholesterol (LDL-c) After 90 Days	2.8 mM Standard Deviation 0.8	2.4 mM Standard Deviation 0.6	2.2 mM Standard Deviation 1.3

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
High Density Lipoprotein Cholesterol (HDL-c) After 90 Days	1.5 mM Standard Deviation 0.3	2.0 mM Standard Deviation 0.3	1.8 mM Standard Deviation 0.5

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Very Low Density Lipoprotein After 90 Days	0.4 mM Standard Deviation 0.1	0.2 mM Standard Deviation 0.0	0.2 mM Standard Deviation 0.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Body Weight (BW) After 90 Days	75.4 kg Standard Deviation 10.2	83.6 kg Standard Deviation 10.7	73.0 kg Standard Deviation 6.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Body Mass Index (BMI) After 90 Days	29.6 kg/m^2 Standard Deviation 4.4	31.8 kg/m^2 Standard Deviation 3.4	28.4 kg/m^2 Standard Deviation 2.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Waist Circumference (WC) After 90 Days	94.0 cm Standard Deviation 11.2	98.0 cm Standard Deviation 12.0	88.7 cm Standard Deviation 9.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Systolic Blood Pressure After 90 Days	122 mmHg Standard Deviation 10	122 mmHg Standard Deviation 13	114 mmHg Standard Deviation 10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Diastolic Blood Pressure After 90 Days	73 mmHg Standard Deviation 8	74 mmHg Standard Deviation 11	72 mmHg Standard Deviation 10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Fasting Serum Glucose (FSG) After 90 Days	5.6 mM Standard Deviation 0.4	5.5 mM Standard Deviation 0.5	5.3 mM Standard Deviation 0.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Uric Acid After 90 Days	285.5 mM Standard Deviation 166.5	350.9 mM Standard Deviation 53.5	279.5 mM Standard Deviation 89.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Berberine n=10 Participants Berberine 500 mg with breakfast, meal, and dinner.	Bezafibrate n=10 Participants Bezafibrate 200 mg with breakfast and dinner.	Berberine Plus Bezafibrate n=10 Participants Berberine 500 mg with breakfast, meal, and dinner, and bezafibrate 200 mg only on breakfast and dinner.
Creatinine After 90 Days	53.0 mM Standard Deviation 26.5	44.2 mM Standard Deviation 35.4	61.9 mM Standard Deviation 35.4

Adverse Events

Berberine

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Bezafibrate

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Berberine Plus Bezafibrate

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Berberine n=12 participants at risk 1500 mg berberine each 24 hours	Bezafibrate n=12 participants at risk 400 mg bezafibrate each 24 hours	Berberine Plus Bezafibrate n=12 participants at risk 1500 mg berberine each 24 hours plus 400 mg bezafibrate each 24 hours
General disorders Headache	8.3% 1/12 • Number of events 1 • adverse events were collected throughout the 90 days of the study	16.7% 2/12 • Number of events 2 • adverse events were collected throughout the 90 days of the study	0.00% 0/12 • adverse events were collected throughout the 90 days of the study
General disorders Dyspepsia	25.0% 3/12 • Number of events 3 • adverse events were collected throughout the 90 days of the study	25.0% 3/12 • Number of events 3 • adverse events were collected throughout the 90 days of the study	16.7% 2/12 • Number of events 2 • adverse events were collected throughout the 90 days of the study
General disorders Nausea	8.3% 1/12 • Number of events 1 • adverse events were collected throughout the 90 days of the study	0.00% 0/12 • adverse events were collected throughout the 90 days of the study	0.00% 0/12 • adverse events were collected throughout the 90 days of the study

Additional Information

Esperanza Martinez Abundis

INSTITUTO DE TERAPÉUTICA EXPERIMENTAL Y CLÍNICA

Phone: 3310585200

Email: esperanzamartnezabundi@yahoo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place