To Study The Influence Of Genomic Factors On Metabolism And Effects Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
To Study The Influence Of Pharmacogenomics Factors On Pharmacokinetics And Pharmacodynamics Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
The purpose of this study is to match the genetic component and clinical attributes of anovulatory patients with response to clomiphene treatment.
By improving our understanding on patient-specific clomiphene response will allow optimization of treatment, reduction of side-effects and shorten the time-to-pregnancy.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Anovulation is the commonest cause for infertility, with clomiphene being the standard treatment. Pharmacogenetic causes of variability in the pharmacokinetics and pharmacodynamics of clomiphene is not well characterized in anovulatory Asian women. Although recent findings suggest that the pharmacokinetics and pharmacodynamics of clomiphene may be influenced by several polygenic pathways involving genes regulating its metabolism (CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C19, CYP2D6), thus contributing significantly to the wide variability in dose-response relationships observed in clinical practice. There has not been objective evidence thus far from an unbiased genome-wide perspective. It is likely that polymorphisms at the CYP cluster of genes encoding for their respective cytochrome proteins may not explain all of the variability with regards to clomiphene's dose-response relationship.
The investigators hypothesize that the pharmacokinetics and pharmacodynamics of clomiphene is under strong control by genetic loci and that these genetic variants could also strongly determine the therapeutic outcome in Asian normogonadotrophic anovulatory patients. The contribution by candidate genes mentioned above will also be clarified in a definitive manner by this study.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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Singapore, Singapur, 229899
- KK Women's and Children's Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Women of reproductive age with ovulatory dysfunction desiring pregnancy,
- Willing to discontinue any form of herbal or traditional chinese medicines for at least three weeks before starting Clomiphene
- Ability to provide written and informed consent taken from participating patients, and
- Willingness to cooperate with study instructions
Exclusion Criteria:
- Pregnant at the time of recruitment,
- Ovarian cysts more than 5cm,
- Abnormal menorrhagia at the time of study recruitment,
- Abnormal liver function or active liver disease,
- Presence of neoplastic lesions of any type,
- Primary pituitary or ovarian failure (Type I and III World Health Organisation [WHO] Infertility)
- Patients with previous treatment with ovulation inducing agents such as follicle stimulating hormone (FSH) and luteinising hormone releasing hormone-analogues (LHRH-analogues);
- Infertility due to other endocrine abnormalities such as hyperprolactinaemia, hypo/hyperthyroidism, premature ovarian failure, diabetes or male factor
- Allergy to clomiphene.
- Fallopian tubal pathology (hydrosalpinges, previous salpingectomies)
- Patients on any drugs with potential to interact with CYP2D6 such as the selective serotonin receptor uptake inhibitors (ex. Venlafaxine, paroxitene, fluoxetine)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: Grupo
- Perspectivas temporales: Futuro
Cohortes e Intervenciones
Grupo / Cohorte |
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Asian Normogonadotrophic Anovulatory Women
Asian women with normal gonadotropin levels but do not ovulate.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Achievement of successful ovulation
Periodo de tiempo: Day 20-23 of menses cycle
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Successful ovulation is defined as a mid-luteal phase serum progesterone level of >20 nmol/L.
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Day 20-23 of menses cycle
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Jerry Chan, MB BCh BaO (Hons) MA,FRCOG,PhD, KK Women's and Children's Hospital
Publicaciones y enlaces útiles
Publicaciones Generales
- Ghobadi C, Gregory A, Crewe HK, Rostami-Hodjegan A, Lennard MS. CYP2D6 is primarily responsible for the metabolism of clomiphene. Drug Metab Pharmacokinet. 2008;23(2):101-5. doi: 10.2133/dmpk.23.101.
- Rostami-Hodjegan A, Lennard MS, Tucker GT, Ledger WL. Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril. 2004 May;81(5):1187-93. doi: 10.1016/j.fertnstert.2003.07.044.
- Murdter TE, Kerb R, Turpeinen M, Schroth W, Ganchev B, Bohmer GM, Igel S, Schaeffeler E, Zanger U, Brauch H, Schwab M. Genetic polymorphism of cytochrome P450 2D6 determines oestrogen receptor activity of the major infertility drug clomiphene via its active metabolites. Hum Mol Genet. 2012 Mar 1;21(5):1145-54. doi: 10.1093/hmg/ddr543. Epub 2011 Nov 22.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2014/RM/001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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