To Study The Influence Of Pharmacogenomics Factors On Pharmacokinetics And Pharmacodynamics Of Clomiphene In Asian Normogonadotrophic Anovulatory Patients.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Achievement of successful ovulation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 43 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Achievement of successful ovulation
时间窗: Day 20-23 of menses cycle
Successful ovulation is defined as a mid-luteal phase serum progesterone level of \>20 nmol/L.
次要结局
未报告次要终点