Human Genomic Population Structure and Phenotype-genotype Variation in ADME Genes in Four Populations
9 de mayo de 2017 actualizado por: Estella S. Poloni
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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
367
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Praha 2, Chequia, 128 43
- Charles University in Prague/Faculty of Science/Department of Anthropology and Human Genetics
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Addis Ababa, Etiopía, P.O.Box 9086
- Addis Ababa University/College of Health Sciences
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Alexandroupolis, Grecia, 68100
- Democritus University of Thrace/School of Health Sciences/University Campus, Dragana
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Muscat, Omán, P. O. Box 50
- Sultan Qaboos University/College of Medicine and Health Sciences/Department of Pharmacology
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 50 años (Adulto)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.);
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Healthy volunteers in Ethiopia
Phenotype and genotype of enzymes involved in drug metabolism in Ethiopia population
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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
DNA sampling from a saliva sample
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Experimental: Healthy volunteers in Oman
Phenotype and genotype of enzymes involved in drug metabolism in Oman population
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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
DNA sampling from a saliva sample
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Experimental: Healthy volunteers in the Czech Republic
Phenotype and genotype of enzymes involved in drug metabolism in Czech Republic population
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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
DNA sampling from a saliva sample
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Experimental: Healthy volunteers in Greece
Phenotype and genotype of enzymes involved in drug metabolism in Greek population
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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
DNA sampling from a saliva sample
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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
Periodo de tiempo: through study completion, an average of 2 years
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Estimation of genotype/allele/haplotype frequencies of variants in genes involved in drug responses
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through study completion, an average of 2 years
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Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
Periodo de tiempo: through study completion, an average of 2 years
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Estimation of frequency distributions of classes of drug metabolizers (metabolizers' profiles: slow/normal/rapid)
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through study completion, an average of 2 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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
Periodo de tiempo: through study completion, an average of 3 year
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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.
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through study completion, an average of 3 year
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Estella S. Poloni, Dr, University of Geneva/Department of Genetics and Evolution
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de noviembre de 2015
Finalización primaria (Actual)
1 de abril de 2017
Finalización del estudio (Actual)
1 de abril de 2017
Fechas de registro del estudio
Enviado por primera vez
11 de mayo de 2016
Primero enviado que cumplió con los criterios de control de calidad
27 de mayo de 2016
Publicado por primera vez (Estimar)
3 de junio de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
10 de mayo de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
9 de mayo de 2017
Última verificación
1 de mayo de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- 15-169
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Indeciso
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