Clinical trial NCT06273241: Impact of Food Intake on Berberine Kinetics
Official title: Impact of Food Intake on Berberine Kinetics - BERKI-3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pharmacokinetic Study in Healthy Volunteers
Keywords: berberine
food effect
pharmacokinetic
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
First posted: 2024-02-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is an unblinded, randomized, prospective study comparing berberine intake in fasted condition and after a high or low caloric meal in a cross-over design.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Berberine plasma concentration fasted vs fed
timeFrame: 24 hours
Secondary outcomes:
measure: Berberine plasma concentrations light vs heavy meal
timeFrame: 24 hours
Other outcomes:
measure: Blood glucose concentrations
timeFrame: 2 hours
measure: Blood insulin concentrations
timeFrame: 2 hours
Locations:
city: Greifswald
country: Germany
facility: University Medicine Greifswald, Institute of Pharmacology
state: Mecklenburg-Vorpommern
Study officials:
affiliation: Universitätsmedizin Greifswald, Institut für Pharmakologie
name: Stefan Engeli, Prof.
role: PRINCIPAL_INVESTIGATOR
References: