Pharmacokinetic Study in Healthy VolunteersBERKI-1NCT05463003
Impact of OCT1 and CYP2D6 Genotypes on Pharmacokinetics of Berberine in Healthy Volunteers
A study testing Berberine in people with Pharmacokinetic Study in Healthy Volunteers, run by University Medicine Greifswald at 1 site in Germany.
Trial summary
This study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers with distinct genotypes of the organic cation transporter 1 (OCT1) gene and the cytochrome P450 2D6 (CYP2D6) gene: Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6… Read more about this study
- Who is it for?
- Ages 18 to 50 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
- 42 participants
- Where
- 1 siteGermany
- Study dates
- 19 Jul 2022to 31 Dec 2022
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- any sex
- OCT1 wildtype: homozygous for OCT*1
- OCT "poor transporter": homozygous or heterozygous for OCT1*3, *4, *5, *6
- CYP2D6 wildtype: homozygous or heterozygous for *1, *2, *35
- CYP2D6 "poor metabolizer": homozygous or heterozygous for *3, *4, *5, *6
- age between 18 and 50 years
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- 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
- a maximum of 3 chronically taken drugs not interfering with OCT1 and CYP2D6 activities
Who cannot join
- BMI > 35 kg/m2 and <18 kg/m2
- known pregnancy or lactation period
- women: positive urine pregnancy test at screening or pharmacokinetic visit
- anemia (hemoglobin < 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)
Show all 9Show fewer
- 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 and regularly draw blood through it
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Medicine Greifswald, Institute of Pharmacology
Greifswald, Mecklenburg-Vorpommern, 17489
About this study
This study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers with distinct genotypes of the organic cation transporter 1 (OCT1) gene and the cytochrome P450 2D6 (CYP2D6) gene:
Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1 wildtype/CYP2D6 deficient genotypes n = 10 Participants will be selected from the study volunteers database of the Institute of Pharmacology in Greifswald according to their OCT1 and CYP2D6 genotypes and to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between Cohort 1a and 2 or Cohort 1b and 3, respectively.
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. A total of 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic activity. At baseline, additional 2x 2.7 ml blood tubes will be collected for DNA isolation.
The total amount of blood collected for each participant is 190 ml at the three Pharmacokinetic Visits and 10 ml at the Screening Visit. Every hour, participants will drink 100 ml of sparkling water to stimulate intestinal peristalsis and promote transport of the capsule. After 2 hours, the participants may drink a cup of tea or coffee and after 4 hours they will be served a meal. Urine will be collected during the first 10 h after administration. Monitoring of vital parameters, e.g. blood pressure and heart rate, will take place for the first 4 hours after administration. The participants will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 hours after administration.
- Being tested
- Berberine
- Keywords
- Berberine, OCT1, CYP2D6, pharmacogenetic, pharmacokinetic
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 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic activity
| Study group | Role | What they receive |
|---|---|---|
| OCT1 and CYP2D6 wildtype genotypes | Active comparator | In this group, the participants are OCT1 and CYP2D6 wildtype genotypes. The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm (cohort) 1 and arm (cohort) 2 and 3, respectively. Receives: Dietary Supplement: Berberine |
| OCT1 deficient and CYP2D6 wildtype genotypes | Active comparator | In this group, the participants are OCT1 deficient and CYP2D6 wildtype genotype. Receives: Dietary Supplement: Berberine |
| OCT1 wildtype and CYP2D6 deficient genotypes | Active comparator | In this group, the participants are OCT1 wildtype and CYP2D6 deficient genotype. Receives: Dietary Supplement: Berberine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Berberine plasma and serum concentration expressed as Area under the Curve (AUC0-48 hours).
Difference in berberine plasma and serum concentrations expressed as Area under the Curve (AUC0-48 hours) between 1) OCT1 wildtype and OCT1 loss of function cohorts (Cohort 1a vs. Cohort 2), and 2) between CYP2D6 wildtype and CYP2D6 loss of function cohorts (Cohort 1b vs. Cohort 3).
Measured: 48 hours
Secondary outcomes (5)
Highest concentration (Cmax) of berberine and the berberine metabolites M1-M9.
Differences in Cmax of berberine and the berberine metabolites M1-M9 between the above described cohorts.
Measured: 48 hours
Time point of highest concentration (Tmax) of berberine and the berberine metabolites M1-M9.
Differences in Tmax of berberine and the berberine metabolites M1-M9 between the above described cohorts.
Measured: 48 hours
Clearance of berberine and the berberine metabolites M1-M9.
Differences in Clearance of berberine and the berberine metabolites M1-M9 between the above described cohorts.
Measured: 48 hours
Apparent volume of distribution of berberine and the berberine metabolites M1-M9.
Differences in apparent volume of distribution of berberine and the berberine metabolites M1-M9 between the above described cohorts.
Measured: 48 hours
Changes of plasma concentrations of known endogenous biomarkers like isobutyrylcarnitine
Changes of plasma concentrations of known endogenous biomarkers like isobutyrylcarnitine. These will be monitored during all time points after berberine administration and their changes over time will be related to the concentration changes of berberine and its major metabolites over time.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2022
- Study start19 Jul 2022
- Primary completion20 Nov 2022
- Study completion31 Dec 2022
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 study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers: Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1 wildtype/CYP2D6 deficient genotypes n = 10
- Masking
- None (open label)
- Enrolment
- 42 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
- NCT05463003
- Sponsor's protocol ID
- IPHA-2022-002
- Acronym
- BERKI-1
- Status last verified
- Dec 2024
- First submitted
- 8 Jul 2022
- Last updated
- 24 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Blocher JA, Meyer-Tonnies MJ, Morof F, Ronnpagel V, Bethmann J, Vollmer M, Engeli S, Tzvetkov MV. Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. Clin Pharmacol Ther. 2025 Jan;117(1):250-260. doi: 10.1002/cpt.3454. Epub 2024 Nov 3.
PubMed 39488825
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of OCT1 and CYP2D6 Genotypes on Pharmacokinetics of Berberine in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05463003
- Acronym / sponsor ID
- BERKI-1 / IPHA-2022-002
- Keywords
- Berberine, OCT1, CYP2D6, pharmacogenetic, pharmacokinetic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- 19 Jul 2022 (actual)
- Primary completion
- 20 Nov 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 18 Jul 2022 (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.
This study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers with distinct genotypes of the organic cation transporter 1 (OCT1) gene and the cytochrome P450 2D6 (CYP2D6) gene:
Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1 wildtype/CYP2D6 deficient genotypes n = 10 Participants will be selected from the study volunteers database of the Institute of Pharmacology in Greifswald according to their OCT1 and CYP2D6 genotypes and to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between Cohort 1a and 2 or Cohort 1b and 3, respectively.
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. A total of 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic activity. At baseline, additional 2x 2.7 ml blood tubes will be collected for DNA isolation.
The total amount of blood collected for each participant is 190 ml at the three Pharmacokinetic Visits and 10 ml at the Screening Visit. Every hour, participants will drink 100 ml of sparkling water to stimulate intestinal peristalsis and promote transport of the capsule. After 2 hours, the participants may drink a cup of tea or coffee and after 4 hours they will be served a meal. Urine will be collected during the first 10 h after administration. Monitoring of vital parameters, e.g. blood pressure and heart rate, will take place for the first 4 hours after administration. The participants will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 hours after administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers: Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1 wildtype/CYP2D6 deficient genotypes n = 10
| Arm | Type | Receives |
|---|---|---|
| OCT1 and CYP2D6 wildtype genotypes | Active comparator | Dietary Supplement: BerberineIn this group, the participants are OCT1 and CYP2D6 wildtype genotypes. The participants are selected to achieve best matching according to sex, age, BMI, alcohol consumption and smoking between arm (cohort) 1 and arm (cohort) 2 and 3, respectively. |
| OCT1 deficient and CYP2D6 wildtype genotypes | Active comparator | Dietary Supplement: BerberineIn this group, the participants are OCT1 deficient and CYP2D6 wildtype genotype. |
| OCT1 wildtype and CYP2D6 deficient genotypes | Active comparator | Dietary Supplement: BerberineIn this group, the participants are OCT1 wildtype and CYP2D6 deficient genotype. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- any sex
- OCT1 wildtype: homozygous for OCT*1
- OCT "poor transporter": homozygous or heterozygous for OCT1*3, *4, *5, *6
- CYP2D6 wildtype: homozygous or heterozygous for *1, *2, *35
- CYP2D6 "poor metabolizer": homozygous or heterozygous for *3, *4, *5, *6
Key exclusion criteria (9 listed)
- BMI > 35 kg/m2 and <18 kg/m2
- known pregnancy or lactation period
- women: positive urine pregnancy test at screening or pharmacokinetic visit
- anemia (hemoglobin < 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)
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 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic activity | Dietary supplement | OCT1 and CYP2D6 wildtype genotypes, OCT1 deficient and CYP2D6 wildtype genotypes, OCT1 wildtype and CYP2D6 deficient genotypes |
Primary outcome
Berberine plasma and serum concentration expressed as Area under the Curve (AUC0-48 hours).
Time frame: 48 hours
Difference in berberine plasma and serum concentrations expressed as Area under the Curve (AUC0-48 hours) between 1) OCT1 wildtype and OCT1 loss of function cohorts (Cohort 1a vs. Cohort 2), and 2) between CYP2D6 wildtype and CYP2D6 loss of function cohorts (Cohort 1b vs. Cohort 3).
5 secondary outcomes
Highest concentration (Cmax) of berberine and the berberine metabolites M1-M9.
Time frame: 48 hours
Time point of highest concentration (Tmax) of berberine and the berberine metabolites M1-M9.
Time frame: 48 hours
Clearance of berberine and the berberine metabolites M1-M9.
Time frame: 48 hours
Apparent volume of distribution of berberine and the berberine metabolites M1-M9.
Time frame: 48 hours
Changes of plasma concentrations of known endogenous biomarkers like isobutyrylcarnitine
Time frame: 48 hours
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 24 Dec 2024.
- Derived from this study: PubMed 39488825Blocher JA, Meyer-Tonnies MJ, Morof F, Ronnpagel V, Bethmann J, Vollmer M, Engeli S, Tzvetkov MV. Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. Clin Pharmacol Ther. 2025 Jan;117(1):250-260. doi: 10.1002/cpt.3454. Epub 2024 Nov 3.
- 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 10 inclusion and 9 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 24 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 and serum concentration expressed as Area under the Curve (AUC0-48 hours). (time frame: 48 hours). 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 NCT05463003, 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 24 Dec 2024.