HealthyNCT02789527
Human Genomic Population Structure and Phenotype-genotype Variation in ADME Genes in Four Populations
A study testing Phenotyping and Genotyping in people with Healthy, run by Estella S. Poloni at 4 sites in 4 countries.
Trial summary
Physicians know that their patients can react differently to the same medical treatment: for some of them, the drug will prove inefficient, whereas for others it might provoke side-effects, sometimes rather serious. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Phenotyping and Genotyping
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 367 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Nov 2015to Apr 2017
- 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
- Women and men in good health
- Aged between 18 and 50 years
- Students or staff in the Academic Institutions where sampling will take place
- With the 2 parents and four grand-parents born to the population;
- Able to provide informed consent
Who cannot join
- Pregnant or breastfeeding women; or women that consider that being pregnant is a possibility;
- Allergic to one of the compounds included in micrococktail (Caffeine, Bupropion, Flurbiprofen, Omeprazole, Dextromethorphan, Midazolam, and Fexofenadine);
- Pedigree related to another volunteer participant (siblings, cousins, uncles/aunts, nephews, etc.);
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Czechia1 site
Charles University in Prague/Faculty of Science/Department of Anthropology and Human Genetics
Prague, 128 43
Ethiopia1 site
Addis Ababa University/College of Health Sciences
Addis Ababa, P.O.Box 9086
Greece1 site
Democritus University of Thrace/School of Health Sciences/University Campus, Dragana
Alexandroupoli, 68100
Oman1 site
Sultan Qaboos University/College of Medicine and Health Sciences/Department of Pharmacology
Muscat, P. O. Box 50
About this study
Official title: Exploratory Study of the Variability, in Five Human Populations, of ADME (Administration, Distribution, Metabolism, Excretion) Genotypes and Phenotypes After the Intake of the "Geneva Micrococktail"
Physicians know that their patients can react differently to the same medical treatment: for some of them, the drug will prove inefficient, whereas for others it might provoke side-effects, sometimes rather serious. Such differences in response to drug intake are due to several factors, of which molecular variations in specific genes, named " ADME " (Absorption, Distribution, Metabolism, Excretion). This project aims at investigating the evolutionary mechanisms responsible for the diversity of ADME genes in human populations. Because of their role at the interface between the organism and its chemical environment, ADME genes are likely targets of recent selective pressures linked to changes in the environments in which humans evolved, such as changes in dietary habits for instance.
The aim of this project is to study the diversity of ADME genes and of their expression in five populations located along a latitudinal axis that extends from East Africa to Central Europe, passing through the Arabian Peninsula and the Mediterranean area, so as to take into account environmental factors that might have influenced the evolution of this diversity. This project is thus intended to evidence the evolutionary mechanisms that shaped genomic regions that are functionally important from the clinical and epidemiological point of view. Moreover, it will allow us to extend the knowledge of human molecular diversity and its evolution to a key-region of the peopling history of our species.
- Conditions
- Healthy
- Being tested
- Phenotyping, Genotyping
- Keywords
- healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenotypingDrug
finger-tip blood drop : enzymatic activities assessed by specific single point concentration ratios after oral intake of the Geneva micrococktail made of : CYP1A2: paraxanthine/caffeine CYP2B6: 4-hydroxybupropion/bupropion CYP2C9: 4-hydroxyflurbiprofen/flurbiprofen CYP2C19: 5-hydroxyomeprazole/omeprazole CYP2D6: dextrorphan/dextromethorphan CYP3A4: 1-hydroxymidazolam/midazolam
GenotypingGenetic
DNA sampling from a saliva sample
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers in Ethiopia | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Ethiopia population Receives: Drug: Phenotyping; Genetic: Genotyping |
| Healthy volunteers in Oman | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Oman population Receives: Drug: Phenotyping; Genetic: Genotyping |
| Healthy volunteers in the Czech Republic | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Czech Republic population Receives: Drug: Phenotyping; Genetic: Genotyping |
| Healthy volunteers in Greece | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Greek population Receives: Drug: Phenotyping; Genetic: Genotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequencies of genotypes and haplotypes of genes involved in drug responses (240,000 Single Nucleotide Polymorphisms) in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Estimation of genotype/allele/haplotype frequencies of variants in genes involved in drug responses
Measured: through study completion, an average of 2 years
Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Estimation of frequency distributions of classes of drug metabolizers (metabolizers' profiles: slow/normal/rapid)
Measured: through study completion, an average of 2 years
Secondary outcomes (1)
Comparison of frequency distributions of variants in genes involved in drug responses and of associated metabolizers' profiles in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Estimation of indices of population genetic/phenotypic diversity and differentiation (expected heterozygosity, Fst). Inferences on the evolutionary mechanisms explaining the estimated diversity among and between populations.
Measured: through study completion, an average of 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study startNov 2015
- Primary completionApr 2017
- Study completionApr 2017
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 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
- 367 participants (actual)
Sponsor and investigators
- Lead sponsor
- Estella S. Poloni
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Sponsor-investigator, Estella S. Poloni, University Hospital, Geneva
- Investigators
- Estella S. Poloni, Dr, Study chair, University of Geneva/Department of Genetics and Evolution
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789527
- Sponsor's protocol ID
- 15-169
- Status last verified
- May 2017
- First submitted
- 11 May 2016
- Last updated
- 10 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Rollason V, Mouterde M, Daali Y, Cizkova M, Priehodova E, Kulichova I, Posova H, Petanova J, Mulugeta A, Makonnen E, Al-Habsi A, Davidson R, Al-Balushi KK, Al-Thihli K, Cerna M, Al-Yahyaee S, Cerny V, Yimer G, Poloni ES, Desmeules J. Safety of the Geneva Cocktail, a Cytochrome P450 and P-Glycoprotein Phenotyping Cocktail, in Healthy Volunteers from Three Different Geographic Origins. Drug Saf. 2020 Nov;43(11):1181-1189. doi: 10.1007/s40264-020-00983-8.
PubMed 32851583
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Study of the Variability, in Five Human Populations, of ADME (Administration, Distribution, Metabolism, Excretion) Genotypes and Phenotypes After the Intake of the "Geneva Micrococktail"
- ClinicalTrials.gov ID
- NCT02789527
- Acronym / sponsor ID
- 15-169
- Conditions
- Healthy
- Keywords
- healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 367 participants (actual)
- Lead sponsor
- Estella S. PoloniUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- Nov 2015 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 3 Jun 2016 (estimated)
- 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.
Physicians know that their patients can react differently to the same medical treatment: for some of them, the drug will prove inefficient, whereas for others it might provoke side-effects, sometimes rather serious. Such differences in response to drug intake are due to several factors, of which molecular variations in specific genes, named " ADME " (Absorption, Distribution, Metabolism, Excretion). This project aims at investigating the evolutionary mechanisms responsible for the diversity of ADME genes in human populations. Because of their role at the interface between the organism and its chemical environment, ADME genes are likely targets of recent selective pressures linked to changes in the environments in which humans evolved, such as changes in dietary habits for instance.
The aim of this project is to study the diversity of ADME genes and of their expression in five populations located along a latitudinal axis that extends from East Africa to Central Europe, passing through the Arabian Peninsula and the Mediterranean area, so as to take into account environmental factors that might have influenced the evolution of this diversity. This project is thus intended to evidence the evolutionary mechanisms that shaped genomic regions that are functionally important from the clinical and epidemiological point of view. Moreover, it will allow us to extend the knowledge of human molecular diversity and its evolution to a key-region of the peopling history of our species.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers in Ethiopia | Experimental | Drug: Phenotyping, Genetic: GenotypingPhenotype and genotype of enzymes involved in drug metabolism in Ethiopia population |
| Healthy volunteers in Oman | Experimental | Drug: Phenotyping, Genetic: GenotypingPhenotype and genotype of enzymes involved in drug metabolism in Oman population |
| Healthy volunteers in the Czech Republic | Experimental | Drug: Phenotyping, Genetic: GenotypingPhenotype and genotype of enzymes involved in drug metabolism in Czech Republic population |
| Healthy volunteers in Greece | Experimental | Drug: Phenotyping, Genetic: GenotypingPhenotype and genotype of enzymes involved in drug metabolism in Greek population |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Women and men in good health
- Aged between 18 and 50 years
- Students or staff in the Academic Institutions where sampling will take place
- With the 2 parents and four grand-parents born to the population;
- Able to provide informed consent
Key exclusion criteria (3 listed)
- Pregnant or breastfeeding women; or women that consider that being pregnant is a possibility;
- Allergic to one of the compounds included in micrococktail (Caffeine, Bupropion, Flurbiprofen, Omeprazole, Dextromethorphan, Midazolam, and Fexofenadine);
- Pedigree related to another volunteer participant (siblings, cousins, uncles/aunts, nephews, etc.);
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 |
|---|---|---|
| Phenotypingfinger-tip blood drop : enzymatic activities assessed by specific single point concentration ratios after oral intake of the Geneva micrococktail made of : CYP1A2: paraxanthine/caffeine CYP2B6: 4-hydroxybupropion/bupropion CYP2C9: 4-hydroxyflurbiprofen/flurbiprofen CYP2C19: 5-hydroxyomeprazole/omeprazole CYP2D6: dextrorphan/dextromethorphan CYP3A4: 1-hydroxymidazolam/midazolam | Drug | Healthy volunteers in Ethiopia, Healthy volunteers in Greece, Healthy volunteers in Oman, Healthy volunteers in the Czech Republic |
| GenotypingDNA sampling from a saliva sample | Genetic | Healthy volunteers in Ethiopia, Healthy volunteers in Greece, Healthy volunteers in Oman, Healthy volunteers in the Czech Republic |
Primary outcome
Frequencies of genotypes and haplotypes of genes involved in drug responses (240,000 Single Nucleotide Polymorphisms) in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Time frame: through study completion, an average of 2 years
Estimation of genotype/allele/haplotype frequencies of variants in genes involved in drug responses
Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Time frame: through study completion, an average of 2 years
Estimation of frequency distributions of classes of drug metabolizers (metabolizers' profiles: slow/normal/rapid)
1 secondary outcome
Comparison of frequency distributions of variants in genes involved in drug responses and of associated metabolizers' profiles in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Time frame: through study completion, an average of 3 year
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 10 May 2017.
- Derived from this study: PubMed 32851583Rollason V, Mouterde M, Daali Y, Cizkova M, Priehodova E, Kulichova I, Posova H, Petanova J, Mulugeta A, Makonnen E, Al-Habsi A, Davidson R, Al-Balushi KK, Al-Thihli K, Cerna M, Al-Yahyaee S, Cerny V, Yimer G, Poloni ES, Desmeules J. Safety of the Geneva Cocktail, a Cytochrome P450 and P-Glycoprotein Phenotyping Cocktail, in Healthy Volunteers from Three Different Geographic Origins. Drug Saf. 2020 Nov;43(11):1181-1189. doi: 10.1007/s40264-020-00983-8.
- 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.
Estella S. Poloni, Dr study chair
University of Geneva/Department of Genetics and Evolution
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phenotyping and Genotyping in people with Healthy, run by Estella S. Poloni at 4 sites in 4 countries.
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 3 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 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Czechia, Ethiopia, Greece, Oman. 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?
Frequencies of genotypes and haplotypes of genes involved in drug responses (240,000 Single Nucleotide Polymorphisms) in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek (time frame: through study completion, an average of 2 years). The study lists 2 primary outcomes in all. 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 NCT02789527, 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 10 May 2017.