HealthyNCT03054220
Impact of Genetic Polymorphism on Drug-Drug Interactions Involving CYP2D6
A study testing Dextromethorphan 5 MG, Tramadol 10 mg and Duloxetine 60mg in people with Healthy, run by Jules Desmeules.
Trial summary
CYP2D6 is characterized by a huge variability in the general population, mainly because of genetic polymorphism and drug-drug interactions (DDIs). CYP2D6 genotype is known to have an impact on the extent of DDIs. Indeed several studies have pointed out differential DDIs extent according to CYP2D6 genotype. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dextromethorphan 5 MG, Tramadol 10 mg and Duloxetine 60mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- No sites listed yet
- Study dates
- Jul 2016to Dec 2018
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women
- Age 18-60 years
- Body Mass Index 18-27
- Understanding of French language and able to give a written inform consent
- CYP2D6 genotype : combination of two fully-functional (normal activity) alleles or of one fully-functional and one non-functional allele (null activity), according to table 1, without gene multiplication
Who cannot join
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP2D6 activity
- Regular smokers of >5 cigarettes/day
- Renal or hepatic impairment
- Medical history of chronic alcoholism or abuse of psychoactive drugs, including opiate addiction
- Liver transplantation
Show all 9Show fewer
- Sensitivity to any of the drugs used
- Alteration of hepatic tests more than 2x normal
- Glomerular filtration rate < 60 ml/min/1.73m2
About this study
Official title: Risk of Phenoconversion in Genetic Extensive Metabolizers Healthy Volunteers Carriers of One Fully-Functional and One Non-Functional Allele Versus Carriers of Two Fully-Functional Alleles
CYP2D6 is characterized by a huge variability in the general population, mainly because of genetic polymorphism and drug-drug interactions (DDIs). CYP2D6 genotype is known to have an impact on the extent of DDIs. Indeed several studies have pointed out differential DDIs extent according to CYP2D6 genotype. The terms phenoconversion and phenotype switch are both used to describe the phenomenon by which a given subject changes his phenotype to another due external influence such as DDIs. When given a sufficiently strong CYP2D6 inhibitor, the phenotype of an individual with no mutant allele (extensive metabolizer, EM) of CYP2D6 can be modified to a poor metabolizer (PM) phenotype. This vulnerability is also thought to be dependent on CYP2D6 genotype. Various combinations of alleles predict an EM genotype, which represents about 60 to 70% of the general population. The aim of the study is to determine whether the presence of genetic mutation in CYP2D6 has an impact on DDIs involving the CYP2D6 enzyme. Our interest focuses on CYP2D6 EM carriers of two fully functional alleles and carriers of one non-functional and one functional allele. In order to elucidate this question, CYP2D6 activity will be measured on healthy volunteers by administration of single low doses of dextromethorphan and tramadol in presence or not of duloxetine and paroxetine, two known CYP2D6 inhibitors.
- Conditions
- Healthy
- Being tested
- Dextromethorphan 5 MG, Tramadol 10 mg, Duloxetine 60mg, Paroxetine 20 mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dextromethorphan 5 MGDrug
Tramadol 10 mgDrug
Duloxetine 60mgDrug
Paroxetine 20 mgDrug
| Study group | Role | What they receive |
|---|---|---|
| CYP2D6 gene score 1 | Experimental | carriers of 1 fully functional and 1non functional CYP2D6 alleles Receives: Drug: Dextromethorphan 5 MG; Drug: Tramadol 10 mg; Drug: Duloxetine 60mg; Drug: Paroxetine 20 mg |
| CYP2D6 gene score 2 | Experimental | carriers of 2 fully functional CYP2D6 alleles Receives: Drug: Dextromethorphan 5 MG; Drug: Tramadol 10 mg; Drug: Duloxetine 60mg; Drug: Paroxetine 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the proportion of volunteers with urinary metabolic ratio Dextromethorphan/Dextrorphan >0.3
Measured: 10 hours
Secondary outcomes (6)
AUC of plasmatic concentrations probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma
Measured: 24 hours
Cmax of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Measured: 24 hours
Tmax of plasmatic concentrations probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Measured: 24 hours
Half-life of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Measured: 24 hours
Clearance of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma
Measured: 24 hours
Difference in the urinary metabolic ratio tramadol/M1
Measured: 10 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study startJul 2016
- Primary completionDec 2018
- Study completionDec 2018
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Desmeules
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jules Desmeules, University Hospital, Geneva
- Investigators
- Jules A Desmeules, Pr, Principal investigator, HUG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03054220
- Sponsor's protocol ID
- 2016-00262
- Other IDs
- 2016
- Status last verified
- Apr 2019
- First submitted
- 6 Feb 2017
- Last updated
- 19 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Phenoconversion in Genetic Extensive Metabolizers Healthy Volunteers Carriers of One Fully-Functional and One Non-Functional Allele Versus Carriers of Two Fully-Functional Alleles
- ClinicalTrials.gov ID
- NCT03054220
- Acronym / sponsor ID
- 2016-00262
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Jules DesmeulesUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 15 Feb 2017 (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 is characterized by a huge variability in the general population, mainly because of genetic polymorphism and drug-drug interactions (DDIs). CYP2D6 genotype is known to have an impact on the extent of DDIs. Indeed several studies have pointed out differential DDIs extent according to CYP2D6 genotype. The terms phenoconversion and phenotype switch are both used to describe the phenomenon by which a given subject changes his phenotype to another due external influence such as DDIs. When given a sufficiently strong CYP2D6 inhibitor, the phenotype of an individual with no mutant allele (extensive metabolizer, EM) of CYP2D6 can be modified to a poor metabolizer (PM) phenotype. This vulnerability is also thought to be dependent on CYP2D6 genotype. Various combinations of alleles predict an EM genotype, which represents about 60 to 70% of the general population. The aim of the study is to determine whether the presence of genetic mutation in CYP2D6 has an impact on DDIs involving the CYP2D6 enzyme. Our interest focuses on CYP2D6 EM carriers of two fully functional alleles and carriers of one non-functional and one functional allele. In order to elucidate this question, CYP2D6 activity will be measured on healthy volunteers by administration of single low doses of dextromethorphan and tramadol in presence or not of duloxetine and paroxetine, two known CYP2D6 inhibitors.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYP2D6 gene score 1 | Experimental | Drug: Dextromethorphan 5 MG, Drug: Tramadol 10 mg, Drug: Duloxetine 60mg, Drug: Paroxetine 20 mgcarriers of 1 fully functional and 1non functional CYP2D6 alleles |
| CYP2D6 gene score 2 | Experimental | Drug: Dextromethorphan 5 MG, Drug: Tramadol 10 mg, Drug: Duloxetine 60mg, Drug: Paroxetine 20 mgcarriers of 2 fully functional CYP2D6 alleles |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy men and women
- Age 18-60 years
- Body Mass Index 18-27
- Understanding of French language and able to give a written inform consent
- CYP2D6 genotype : combination of two fully-functional (normal activity) alleles or of one fully-functional and one non-functional allele (null activity), according to table 1, without gene multiplication
Key exclusion criteria (9 listed)
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP2D6 activity
- Regular smokers of >5 cigarettes/day
- Renal or hepatic impairment
- Medical history of chronic alcoholism or abuse of psychoactive drugs, including opiate addiction
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 MG | Drug | CYP2D6 gene score 1, CYP2D6 gene score 2 |
| Tramadol 10 mg | Drug | CYP2D6 gene score 1, CYP2D6 gene score 2 |
| Duloxetine 60mg | Drug | CYP2D6 gene score 1, CYP2D6 gene score 2 |
| Paroxetine 20 mg | Drug | CYP2D6 gene score 1, CYP2D6 gene score 2 |
Primary outcome
Difference in the proportion of volunteers with urinary metabolic ratio Dextromethorphan/Dextrorphan >0.3
Time frame: 10 hours
6 secondary outcomes
AUC of plasmatic concentrations probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma
Time frame: 24 hours
Cmax of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Time frame: 24 hours
Tmax of plasmatic concentrations probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Time frame: 24 hours
Half-life of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma and tramadol) and their metabolites in plasma
Time frame: 24 hours
Clearance of probe drugs (dextromethorphan and tramadol) and their metabolites and tramadol) and their metabolites in plasma
Time frame: 24 hours
Difference in the urinary metabolic ratio tramadol/M1
Time frame: 10 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 19 Apr 2019.
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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.
Jules A Desmeules, Pr principal investigator
HUG
Questions about this trial
What is this clinical trial studying?
A study testing Dextromethorphan 5 MG, Tramadol 10 mg and Duloxetine 60mg in people with Healthy, run by Jules Desmeules.
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 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 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Difference in the proportion of volunteers with urinary metabolic ratio Dextromethorphan/Dextrorphan >0.3 (time frame: 10 hours). 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 19 Apr 2019.