Sex Differences in Berberine Pharmacokinetics

NCT05845931 | Completed

• 1 other identifier: IPHA-2023-006
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetic Study in Healthy Volunteers

Keywords

Berberine; Sex differences; pharmacokinetic; menstrual cycle

Outcome Measures

Primary Outcomes (1)

• Berberine plasma concentration women vs. men

  Difference in berberine plasma concentrations expressed as Area under the Curve between women and men.

  day 1

Secondary Outcomes (1)

• Berberine plasma concentrations durig first and second half of the menstrual cycle

  day 1

Study Arms (2)

woman

ACTIVE COMPARATOR

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

men

ACTIVE COMPARATOR

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

Interventions

Berberine DIETARY_SUPPLEMENT

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).

men; woman

Eligibility Criteria

• Age: 18 Years - 35 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medicine Greifswald: lead

Study Sites (1)

Center of Drug Absorption and Transport (C_DAT)

Greifswald, Mecklenburg-Vorpommern, 17489, Germany

Location

Related Publications (1)

• Yao Q, Wei T, Qiu H, Cai Y, Yuan L, Liu X, Li X. Epigenetic Effects of Natural Products in Inflammatory Diseases: Recent Findings. Phytother Res. 2025 Jan;39(1):90-137. doi: 10.1002/ptr.8364. Epub 2024 Nov 8.

  PMID: 39513382 DERIVED

MeSH Terms

Interventions

Berberine

Intervention Hierarchy (Ancestors)

Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stefan Engeli, Prof.

  Universitätsmedizin Greifswald, Institut für Pharmakologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This Study will be an open label study. Participants will be selected from an existing database of our Institute.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med Stefan Engeli

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

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 6, 2023
• Study Start: May 5, 2023
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)