HealthyENDOCYP2D6NCT04188028
Endobiotics for Phenotyping of Human Cytochrome P450 Enzymes
A study testing Dextromethorphan 5 MG, Paroxetine 10Mg Tablet and Paroxetine 20Mg Tablet in people with Healthy, run by Jules Desmeules at 1 site in Switzerland.
Trial summary
CYP2D6 metabolizes ~25% of all marketed drugs. There is an important variability in the activity of this enzyme among individuals. The cause of this variability might be environmental, genetic, ethnical or even related to a disease. The administration of a CYP2D6 probe drug (e.g. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dextromethorphan 5 MG, Paroxetine 10Mg Tablet and Paroxetine 20Mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jan 2019to 31 Dec 2019
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and women
- Age 18-65 years
- Body Mass Index (BMI) 18-27
- Understanding of French language and able to give a written inform consent
- CYP2D6 genotype : activity score = 0 (PMs) or activity score ≥ 1 (EMs-UMs)
- Reliable contraception during the whole study, including a barrier method
Who cannot join
- Participation in any other interventional clinical study within 3 months prior to inclusion
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP activity (based on the 'drug interactions and cytochromes P450' table published by the Service of Clinical Pharmacology and Toxicology, HUG54 and on the investigator's knowledge)
- Regular smokers of ≥ 10 cigarettes/day
- Alcohol intake 2 days prior to session 1 and during paroxetine intake
- Medical history of chronic alcoholism or abuse of psychoactive drugs
Show all 11Show fewer
- Regular use of psychotropic substances
- Sensitivity to any of the drugs used
- Alteration of hepatic tests (ASAT, ALAT, BILI, GGT) more than 3x normal
- Psychiatric disorders
- Beck Score ≥10 (question related to suicide >0)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Endobiotics for Phenotyping of Human Cytochrome P450 Enzymes: Use of Metabolomics for the Identification of New CYP2D6 Endogenous Biomarkers in Healthy Volunteers
CYP2D6 metabolizes ~25% of all marketed drugs. There is an important variability in the activity of this enzyme among individuals. The cause of this variability might be environmental, genetic, ethnical or even related to a disease. The administration of a CYP2D6 probe drug (e.g. dextromethorphan) is a good way to characterize CYP2D6 phenotype. Nonetheless, it is relatively invasive and the vulnerable population (e.g. pregnant women) cannot be phenotyped in this manner. Therefore, finding an endogenous substance which is metabolized by CYP2D6 could replace usual phenotyping procedure using a probe drug. This study evaluates the impact of a CYP2D6 inhibitor and of genetic polymorphism on the metabolome of healthy volunteers in order to identify new CYP2D6 biomarkers. To this end, untargeted metabolomics analysis using LC-HRMS will be performed on plasma and urine samples This single-centre open-label clinical trial will include 40 healthy subjects (men and women) between 18 and 65 years. Eligible participants will be assigned to a study group according to their CYP2D6 genotypes: poor metabolizers (PMs) and extensive/ultrarapid metabolizers (EMs-UMs). Two sessions will take place for each subjects.
Session 1: CYP2D6 phenotyping (dextromethorphan 5 mg, single dose) Session 2: idem session 1 with prior uptake of a CYP2D6 inhibitor (paroxetine 10 or 20 mg, one dose a day for 7 days).
In both sessions, urine will be collected up to 24 hours and capillary/venous blood will be sampled before phenotyping for metabolomics analyses. Urine will also be collected for 4 hours after dextromethorphan intake in order to phenotype the CYP2D6 enzyme.
- Conditions
- Healthy
- Being tested
- Dextromethorphan 5 MG, Paroxetine 10Mg Tablet, Paroxetine 20Mg Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dextromethorphan 5 MGDrug
dextromethorphan 5 mg po
Paroxetine 10Mg TabletDrug
Paroxetine 10 mg po
Paroxetine 20Mg TabletDrug
Paroxetine 20 mg po
| Study group | Role | What they receive |
|---|---|---|
| CYP2D6 gene score 0 | Experimental | CYP2D6 gene score 0: carrier of two non-functional alleles Receives: Drug: Dextromethorphan 5 MG; Drug: Paroxetine 10Mg Tablet |
| CYP2D6 gene score ≥1 | Experimental | CYP2D6 gene score ≥1: carrier of one fully-functional and one non-functional allele of CYP2D6 , one fully-functional and one reduced-function of CYP2D6, two fully-functional alleles of CYP2D6 or more than two functional alleles alleles Receives: Drug: Dextromethorphan 5 MG; Drug: Paroxetine 20Mg Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify endogenous markers of CYP2D6 activity in urine and plasma using untargeted metabolomics
Metabolomic strategie (LC-Q-Exactive HRMS) will be used to identify and characterize endogenous compounds that correlate with the urinary metabolic ratio dextromethorphan/dextrorphan before and after administration of paroxetine, a strong CYP2D6 inhibitor.
Measured: 7 days
Secondary outcomes (2)
Difference in DEM/DOR urinary ratio before and after administration of paroxetine
Measured: 7 days
Correlation of significant ions with DEM/DOR urinary ratio or CYP2D6 activity score
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2019
- Study start1 Jan 2019
- Primary completion31 Jul 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Desmeules
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jules Desmeules, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04188028
- Sponsor's protocol ID
- 2018-01637
- Other IDs
- 2018
- Acronym
- ENDOCYP2D6
- Status last verified
- Jan 2022
- First submitted
- 18 Apr 2019
- Last updated
- 4 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endobiotics for Phenotyping of Human Cytochrome P450 Enzymes: Use of Metabolomics for the Identification of New CYP2D6 Endogenous Biomarkers in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04188028
- Acronym / sponsor ID
- ENDOCYP2D6 / 2018-01637
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Jules DesmeulesUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 5 Dec 2019 (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.
CYP2D6 metabolizes ~25% of all marketed drugs. There is an important variability in the activity of this enzyme among individuals. The cause of this variability might be environmental, genetic, ethnical or even related to a disease. The administration of a CYP2D6 probe drug (e.g. dextromethorphan) is a good way to characterize CYP2D6 phenotype. Nonetheless, it is relatively invasive and the vulnerable population (e.g. pregnant women) cannot be phenotyped in this manner. Therefore, finding an endogenous substance which is metabolized by CYP2D6 could replace usual phenotyping procedure using a probe drug. This study evaluates the impact of a CYP2D6 inhibitor and of genetic polymorphism on the metabolome of healthy volunteers in order to identify new CYP2D6 biomarkers. To this end, untargeted metabolomics analysis using LC-HRMS will be performed on plasma and urine samples This single-centre open-label clinical trial will include 40 healthy subjects (men and women) between 18 and 65 years. Eligible participants will be assigned to a study group according to their CYP2D6 genotypes: poor metabolizers (PMs) and extensive/ultrarapid metabolizers (EMs-UMs). Two sessions will take place for each subjects.
Session 1: CYP2D6 phenotyping (dextromethorphan 5 mg, single dose) Session 2: idem session 1 with prior uptake of a CYP2D6 inhibitor (paroxetine 10 or 20 mg, one dose a day for 7 days).
In both sessions, urine will be collected up to 24 hours and capillary/venous blood will be sampled before phenotyping for metabolomics analyses. Urine will also be collected for 4 hours after dextromethorphan intake in order to phenotype the CYP2D6 enzyme.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYP2D6 gene score 0 | Experimental | Drug: Dextromethorphan 5 MG, Drug: Paroxetine 10Mg TabletCYP2D6 gene score 0: carrier of two non-functional alleles |
| CYP2D6 gene score ≥1 | Experimental | Drug: Dextromethorphan 5 MG, Drug: Paroxetine 20Mg TabletCYP2D6 gene score ≥1: carrier of one fully-functional and one non-functional allele of CYP2D6 , one fully-functional and one reduced-function of CYP2D6, two fully-functional alleles of CYP2D6 or more than two functional alleles alleles |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy men and women
- Age 18-65 years
- Body Mass Index (BMI) 18-27
- Understanding of French language and able to give a written inform consent
- CYP2D6 genotype : activity score = 0 (PMs) or activity score ≥ 1 (EMs-UMs)
Key exclusion criteria (11 listed)
- Participation in any other interventional clinical study within 3 months prior to inclusion
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP activity (based on the 'drug interactions and cytochromes P450' table published by the Service of Clinical Pharmacology and Toxicology, HUG54 and on the investigator's knowledge)
- Regular smokers of ≥ 10 cigarettes/day
- Alcohol intake 2 days prior to session 1 and during paroxetine intake
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 |
|---|---|---|
| Dextromethorphan 5 MGdextromethorphan 5 mg po | Drug | CYP2D6 gene score 0, CYP2D6 gene score ≥1 |
| Paroxetine 10Mg TabletParoxetine 10 mg po | Drug | CYP2D6 gene score 0 |
| Paroxetine 20Mg TabletParoxetine 20 mg po | Drug | CYP2D6 gene score ≥1 |
Primary outcome
Identify endogenous markers of CYP2D6 activity in urine and plasma using untargeted metabolomics
Time frame: 7 days
Metabolomic strategie (LC-Q-Exactive HRMS) will be used to identify and characterize endogenous compounds that correlate with the urinary metabolic ratio dextromethorphan/dextrorphan before and after administration of paroxetine, a strong CYP2D6 inhibitor.
2 secondary outcomes
Difference in DEM/DOR urinary ratio before and after administration of paroxetine
Time frame: 7 days
Correlation of significant ions with DEM/DOR urinary ratio or CYP2D6 activity score
Time frame: 7 days
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 4 Jan 2022.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dextromethorphan 5 MG, Paroxetine 10Mg Tablet and Paroxetine 20Mg Tablet in people with Healthy, run by Jules Desmeules at 1 site in Switzerland.
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 6 inclusion and 11 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 4 Jan 2022. 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 Switzerland. 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?
Identify endogenous markers of CYP2D6 activity in urine and plasma using untargeted metabolomics (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jan 2022; AzTrials last refreshed its copy on 8 Nov 2026.