Impact of Food Intake on Berberine Kinetics (BERKI-3)

Impact of Food Intake on Berberine Kinetics - BERKI-3

The influence of genetic variants of the CYP2D6 enzyme and the Organic Cation Transporter 1 (OCT-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 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, the participants 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, the investigators 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 healthy volunteers with an equal ratio of man and women will be enrolled.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetic Study in Healthy Volunteers
• Intervention / Treatment: Other: food intake

Detailed 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 toasts, butter, cheese, marmalade), or a high caloric meal (2 toasts 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.

A total amount of 12 blood samples at defined time points (baseline; 1; 2; 3; 4; 5; 6; 7; 8; 24 h) will be taken. At each time point, blood will be collected in a tube for collecting plasma. In addition, for glucose and insulin measurements, blood samples will be obtained 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 participants will be served tea or coffee and after 4 h a meal will be served.

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17487
      • University Medicine Greifswald, Institute of Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• wildtype genotypes for CYP2D6 and organic cation transporter 1 (OCT-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 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
• anemia: 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Berberine intake in fasted condition; Intake of 1000 mg berberine in the fasted condition (intake of last meal: before 20:00 on the day before the study visit)	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. A total amount of 12 blood samples at defined time points (baseline; 1; 2; 3; 4; 5; 6; 7; 8; 24 h) will be taken. For glucose and insulin measurements, blood samples will be obtained at 4 h, 5 h and 6 h .
Active Comparator: Berberine intake after a low caloric meal; Intake of 1000 mg berberine after a light caloric meal (2 toasts, butter, cheese, marmalade)	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. A total amount of 12 blood samples at defined time points (baseline; 1; 2; 3; 4; 5; 6; 7; 8; 24 h) will be taken. For glucose and insulin measurements, blood samples will be obtained at 4 h, 5 h and 6 h .
Active Comparator: Berberine intake after a high caloric meal; Intake of 1000 mg berberine after a high caloric meal (2 toasts with butter, 2 fried eggs, 2 slices of bacon, 3 hash brown and 240ml of whole milk)	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. A total amount of 12 blood samples at defined time points (baseline; 1; 2; 3; 4; 5; 6; 7; 8; 24 h) will be taken. For glucose and insulin measurements, blood samples will be obtained at 4 h, 5 h and 6 h .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose concentrations	AUC of blood glucose over two hours after single doses of berberine, both in the fasted and fed condition.	2 hours
Blood insulin concentrations	AUC of blood insulin over two hours after single doses of berberine, both in the fasted and fed condition.	2 hours

Collaborators and Investigators

• Sponsor: University Medicine Greifswald
• Investigators: Principal Investigator: Stefan Engeli, Prof., Universitätsmedizin Greifswald, Institut für Pharmakologie

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Actual): May 11, 2024
• Study Completion (Actual): May 11, 2024

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: pharmacokinetic; food effect; berberine
• Other Study ID Numbers: IPHA-2024-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No