Pharmacokinetic Study in Healthy VolunteersBERKI-2NCT05845931
Sex Differences in Berberine Pharmacokinetics
A study testing Berberine in people with Pharmacokinetic Study in Healthy Volunteers, run by University Medicine Greifswald at 1 site in Germany.
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. By chance, a significant sex difference was observed independent of the genetic variant. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetic Study in Healthy Volunteers
- What is being tested?
- Berberine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 5 May 2023to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Center of Drug Absorption and Transport (C_DAT)
Greifswald, Mecklenburg-Vorpommern, 17489
About this study
Official title: Sex Differences in Berberine Pharmacokinetics in Healthy Volunteers - BERKI-2
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.
Read the 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 at 8 a.m.. 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. Between 2 and 4 p.m., measuring body composition by bioelectrical impedance analysis (BIA) will be peformed to obtain fat mass and fat free mass (total and percentage) and body water. We use the seca mBCA 525 scale.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.
- Being tested
- Berberine
- Keywords
- Berberine, Sex differences, pharmacokinetic, menstrual cycle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerberineDietary 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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Berberine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Berberine plasma concentration women vs. men
Difference in berberine plasma concentrations expressed as Area under the Curve between women and men.
Measured: day 1
Secondary outcomes (1)
Berberine plasma concentrations durig first and second half of the menstrual cycle
Difference in berberine plasma concentrations expressed as Area under the Curve between the 1st and the 2nd phase of the female menstrual cycle.
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start5 May 2023
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pharmacokinetic Study in Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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 applied
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefan Engeli, MD, University Medicine Greifswald
- Investigators
- Stefan Engeli, Prof., Principal investigator, Universitätsmedizin Greifswald, Institut für Pharmakologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05845931
- Sponsor's protocol ID
- IPHA-2023-006
- Acronym
- BERKI-2
- Status last verified
- Dec 2024
- First submitted
- 24 Apr 2023
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39513382
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex Differences in Berberine Pharmacokinetics in Healthy Volunteers - BERKI-2
- ClinicalTrials.gov ID
- NCT05845931
- Acronym / sponsor ID
- BERKI-2 / IPHA-2023-006
- Keywords
- Berberine, Sex differences, pharmacokinetic, menstrual cycle
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- 5 May 2023 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 6 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 at 8 a.m.. 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. Between 2 and 4 p.m., measuring body composition by bioelectrical impedance analysis (BIA) will be peformed to obtain fat mass and fat free mass (total and percentage) and body water. We use the seca mBCA 525 scale.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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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 applied
| Arm | Type | Receives |
|---|---|---|
| woman | Active comparator | Dietary Supplement: BerberineThe participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2. |
| men | Active comparator | Dietary Supplement: BerberineThe participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm 1 and arm 2. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerberineA 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). | Dietary supplement | men, woman |
Primary outcome
Berberine plasma concentration women vs. men
Time frame: day 1
Difference in berberine plasma concentrations expressed as Area under the Curve between women and men.
1 secondary outcome
Berberine plasma concentrations durig first and second half of the menstrual cycle
Time frame: day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Derived from this study: PubMed 39513382Yao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Engeli, Prof. principal investigator
Universitätsmedizin Greifswald, Institut für Pharmakologie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Berberine in people with Pharmacokinetic Study in Healthy Volunteers, run by University Medicine Greifswald at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Berberine plasma concentration women vs. men (time frame: day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05845931, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.