Impact of Food Intake on Berberine Kinetics

Pharmacokinetic Study in Healthy Volunteers Clinical Trial

— BERKI-3  

Official title:

Impact of Food Intake on Berberine Kinetics - BERKI-3

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06273241
• Other study ID #: IPHA-2024-009
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 4, 2024
• Est. completion date: September 30, 2024

Study information

• Verified date: February 2024
• Source: University Medicine Greifswald
• Contact: Stefan Engeli, Prof.
• 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. A significant sex difference was observed. These results lead to the BERKI-2 study, investigating the influence of the female hormonal cycle on berberine kinetics. In this study, women took a single berberine dose once in the first and once in the second half of their menstrual cycle, men served as a control group ingesting a single berberine dose. Contrary to our expectations, the previously observed sex difference could not be confirmed.

In both BERKI-1 and 2 studies, the plasma concentration curve exhibited two peaks. The first after about 2-3 h, and the second after approximately 5 h of berberine intake. All participants took a single dose of Berberine under fasting conditions in the morning and 4 h after berberine intake, they ate a meal. Shortly after meal intake, the plasma concentration curve peaked again BERKI-3 will investigate the impact of food intake on berberine bioavailability and the kinetic properties. Given the suspected influence of berberine on glycemic control, we will also measure insulin and glucose after the meal at noon.

As in BERKI-1 and 2, time dependent blood and urine samples will be collected after a single berberine dose. One By measuring berberine metabolites by Liquid Chromatography and Mass-spec One dose will be taken in the fasted condition and the other two after a light or high caloric meal, respectively.

24 heathy volunteers with an equal ratio of man and women will be enrolled.

Description:

All enrolled participants will come under fasting conditions for 10 h to the Clinical Research Unit. Every volunteer will receive a single dose of 1000 mg berberine (two capsules) with 250 ml still water. Intake will be either in the fasting condition, or after a light caloric meal (2 toast, butter, cheese, marmalade), or a high caloric meal (2 toast with butter, 2 fried eggs, 2 slices of bacon, 3 hash brown and 240ml of whole milk), respectively. In between these different intakes will be at least one week. The order of fasting - light meal - heavy meal study visits will be randomized.

We will take a total amount of 12 blood samples at defined time points (baseline; 1; 2; 3; 4; 5; 6; 7; 8; 24 h). At each time point, blood will be collected in a tube for collecting plasma. In addition, for glucose and insulin measurements, we will obtain blood samples at 4 h, 5 h and 6 h.

Every hour until the meal at noon, participants will drink 100 ml of sparkling water to stimulate the intestinal peristalsis and promote transport of the capsule. Volunteers are asked to stay in bed for four hours after berberine intake but then are allowed to move freely in the Clinical Research Unit. After 2 h they will be served tea or coffee and after 4 h they will be served a meal.

Urine will be collected at the first 8 h after administration. The participants will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 8 hours after administration.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• wildtype genotypes for CYP2D6 and OCT1

• 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 orthopedic diseases

Exclusion Criteria:

• BMI =18,5kg/m2 and =29,9 kg/m2

• only in women: known pregnancy or lactation period

• only in women: positive pregnancy test at screening or any other study visit

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

• elevated liver function tests (ALAT, ASAT, yGT, Bilirubin > 2xULN)

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

• currently mentally unstable

• use of recreational drugs more than twice a week

• poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it

Related Conditions & MeSH terms

• Pharmacokinetic Study in Healthy Volunteers

Intervention

Other:
• food intake
A single dose of 1000 mg berberine in two capsules will be administered with 250 ml of still water in the overnight fasting condition as the control condition. The two intervention arms will test the effect of different meals on berberine kinetics..

Locations

Country	Name	City	State
Germany	University Medicine Greifswald, Institute of Pharmacology	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
Other	Blood glucose concentrations	AUC of blood glucose over two hours after single doses of berberine, both in the fasted and fed condition.	2 hours
Other	Blood insulin concentrations	AUC of blood insulin over two hours after single doses of berberine, both in the fasted and fed condition.	2 hours
Primary	Berberine plasma concentration fasted vs fed	Difference of berberine plasma concentrations between the fasted and fed condition, expressed as area under the curve (AUC0-24h).	24 hours
Secondary	Berberine plasma concentrations light vs heavy meal	Difference of berberine plasma concentrations after a light and heavy meal, expressed as area under the curve (AUC0-24h).	24 hours