Sex Differences in Berberine Pharmacokinetics

Pharmacokinetic Study in Healthy Volunteers Clinical Trial

— BERKI-2  

Official title:

Sex Differences in Berberine Pharmacokinetics in Healthy Volunteers - BERKI-2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05845931
• Other study ID #: IPHA-2023-006
• Status: Recruiting
• Phase: N/A
• Start date: May 5, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2023
• Source: University Medicine Greifswald
• Contact: Stefan Engeli, Prof. Dr. med.
• Phone: +49 3834865633
• Email: stefan.engeli[@]med.uni-greifswald.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The influence of genetic variants of the CYP2D6 enzyme and the Organic Cation Transporter 1 on the kinetics of berberine (BERKI-1) has recently been studied. By chance, a significant sex difference was observed independent of the genetic variant. The Area under the curve of berberine in women compared to men was about three times higher, and the difference was statistically significant

The aim of BERKI-2 is to confirm the sex difference in an independent second study. In addition, influences of sex hormones on berberine kinetics in women will be studied.

As in BERKI-1, time-dependent blood and urine samples will be collected after a single berberine dose. By measuring berberine metabolites by Liquid Chromatography and Mass-spectrometry standard kinetic parameters e.g., AUC0-24, Cmax, Tmax will be calculated. Age-matched healthy women (n = 15) and men (n = 15) will be enroled.

Description:

A single dose of 1000 mg berberine will be administered in two capsules with 250 ml of still water in the overnight fasting condition at 8 a.m.. A total of 11 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine concentrations. Another serum sample will be obtained at baseline from women only to determine estradiol, progesterone, luteinizing hormone and follicle stimulating hormone to characterize the first and second phase of the cycle.

Every hour, participants will drink 100 ml of sparkling water to stimulate intestinal peristalsis and promote transport of the capsule. Volunteers are asked to stay in bed during the first four hours but are then allowed to move freely within the Clinical Research Unit. After 2 h, participants may drink a cup of tea or coffee and after 4 h they will be served a meal. Urine will be collected during the first 10 h after administration. Between 2 and 4 p.m., measuring body composition by bioelectrical impedance analysis (BIA) will be peformed to obtain fat mass and fat free mass (total and percentage) and body water. We use the seca mBCA 525 scale.The participants will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 h after administration.

Women will undergo this treatment twice at least one week apart. Once in the first half (between days 4-10 after start of menstrual bleeding) and once in the second half (between days 20-26 after start of menstrual bleeding) of their menstrual cycle. The first day of menstrual bleeding marks day 1 as a reference.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• wild type genotypes for CYP2D6 and Organic Cation Transporter 1

• understands the study purpose and design

• contractually capable and provides signed informed consent form

• healthy condition or mild and/or well treated forms of allergies, asthma, hypertension, and orthopaedic diseases

• no regular use of more than 2 drugs

Exclusion Criteria:

• volunteers who have already participated in BERKI-1

• BMI <18 kg/m2 and >35 kg/m2

• disorders of sex hormone regulation, hormone treatments

• women: menopause,known pregnancy or lactation period, positive urine pregnancy test at screening and at visits, oral contraceptives, depot contraceptives, or hormone-re-leasing intrauterine devices

• anaemia (haemoglobin < 13 g/dl (8,07 mmol/l) in men or < 12 g/dl (7,45 mmol/l) in women

• elevated liver function tests (> 2x ULN)

• reduced renal function (eGFRMDRD < 60 ml/min/1,7m2)

• psychiatric disease or drug dependency at time of visit

• use of recreational drugs more than twice a week

• poor venous conditions that make it impossible to place a peripheral venous catheter

Related Conditions & MeSH terms

• Pharmacokinetic Study in Healthy Volunteers

Intervention

Dietary Supplement:
• Berberine
A single dose of 1000 mg berberine in two capsules will be administered with 250 ml of still water in the overnight fasting condition. A total of 11 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine concentrations. (Women will undergo the Intervention twice, once in the 1st half and once in the 2nd half of their menstrual cycle.) In addition urine will be collected over the time of 0-10 h after berberine intake and body composition will be measured by bioelectrical impedance analysis (BIA).

Locations

Country	Name	City	State
Germany	Center of Drug Absorption and Transport (C_DAT)	Greifswald	Mecklenburg-Vorpommern

Sponsors (1)

Lead Sponsor	Collaborator
University Medicine Greifswald

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Berberine plasma concentration women vs. men	Difference in berberine plasma concentrations expressed as Area under the Curve between women and men.	day 1
Secondary	Berberine plasma concentrations durig first and second half of the menstrual cycle	Difference in berberine plasma concentrations expressed as Area under the Curve between the 1st and the 2nd phase of the female menstrual cycle.	day 1