Clinical trial NCT02789527: Human Genomic Population Structure and Phenotype-genotype Variation in ADME Genes in Four Populations
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"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: healthy volunteers
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2016-06-03
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.);

Primary outcomes:
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
timeFrame: through study completion, an average of 2 years
measure: Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: 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
timeFrame: through study completion, an average of 3 year
Other outcomes:
Locations:
city: Praha 2
country: Czechia
facility: Charles University in Prague/Faculty of Science/Department of Anthropology and Human Genetics
city: Addis Ababa
country: Ethiopia
facility: Addis Ababa University/College of Health Sciences
city: Alexandroupolis
country: Greece
facility: Democritus University of Thrace/School of Health Sciences/University Campus, Dragana
city: Muscat
country: Oman
facility: Sultan Qaboos University/College of Medicine and Health Sciences/Department of Pharmacology
Study officials:
affiliation: University of Geneva/Department of Genetics and Evolution
name: Estella S. Poloni, Dr
role: STUDY_CHAIR
References:
citation: 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.