BERKI-2: Sex Differences in Berberine Pharmacokinetics

Sponsor

University Medicine Greifswald (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05845931

Collaborator

(none)

Enrollment

Arms

8.2

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetic Study in Healthy Volunteers	Dietary Supplement: Berberine	N/A

Detailed 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. 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. 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is an unblinded, non-randomized, prospective Kinetic study comparing age-matched women and men (parallel). In women, an additional cross-over approach is appliedThis is an unblinded, non-randomized, prospective Kinetic study comparing age-matched women and men (parallel). In women, an additional cross-over approach is applied

Masking:

None (Open Label)

Masking Description:

This Study will be an open label study. Participants will be selected from an existing database of our Institute.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 24, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: woman The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2.	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 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 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.)
Active Comparator: men The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2.	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 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 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.)

Arm

Intervention/Treatment

Active Comparator: woman

The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2.

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 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 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.)

Active Comparator: men

The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2.

Dietary Supplement: Berberine

Outcome Measures

Primary Outcome Measures

Berberine plasma concentration women vs. men [day 1]
Difference in berberine plasma concentrations expressed as Area under the Curve between women and men.

Secondary Outcome Measures

Berberine plasma concentrations durig first and second half of the menstrual cycle [day 1]
Difference in berberine plasma concentrations expressed as Area under the Curve between the 1st and the 2nd phase of the female menstrual cycle.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 30 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University Medicine Greifswald

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Stefan Engeli, MD, Prof. Dr. med Stefan Engeli, University Medicine Greifswald

ClinicalTrials.gov Identifier:

NCT05845931

Other Study ID Numbers:

IPHA-2023-006

First Posted:

May 6, 2023

Last Update Posted:

May 6, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Stefan Engeli, MD, Prof. Dr. med Stefan Engeli, University Medicine Greifswald

Study Results

No Results Posted as of May 6, 2023