Determinaton of Changes in the Endometrial Gene Expression Profile Induced by Exogenous Progesterone After Post-ovulatory Administration of Mifepristone
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Endometrial Gene Expression Profile
研究概览
简要总结
The goal of this exploratory trial is to determine the endometrial gene expression profile induced by exogenous progesterone after postovulatory administration of mifepristone. It will also learn about the plasticity ofr the endometrial response to progesterone. The main questions it aims to answer are:
Is exogenous progesterone able to modulate the gene expression of endometrial transcripts that have been altered by mifepristone?
Researchers will compare the endometrial gene expression profiles with exogeonous progesterone to a placebo (a look-alike substance that contains no drug) after postovulatory administration of mifepristone.
Participants will:
Do ovulation follow-up tests at home assesing LH in urine Visit the hospital 2 days after a positive LH for mifepristone administration and ultrasonography check of ovaries and uterus.
Starting from the next day, take progesterone or placebo for 3 days. Visit the hospital 2 days after that for ultrasonography check of ovaries and uterus and for an endometrial and blood sample collection.
The endometrial samples will be processed to isolate the RNA and for histological assessment. Gene expression profiles will be determined by RNA-seq.
详细描述
Objective
To determine the effect of progesterone supplementation on the mid-secretory endometrial transcript profile after postovulatory administration of mifepristone.
Design: A randomized, double-blind, placebo-controlled study. Setting: Tertiary academic medical center Subjects: A total of 9 Hispanic women of proven fertility who had been surgically sterilized.
Interventions: Participating women received a single dose of mifepristone 200mg 48 hours after the LH peak (LH+2, LH+0=LH peak). Endometrial samples were obtained on LH+7 after vaginal administration of micronized progesterone (600mg/day) for 3 days (LH+3 to LH+5). Each woman contributed with one cycle treated with placebo and another with progesterone (group A). Additionally, endometrial samples were obtained on LH+7 from subset of 4 women who did not receive mifepristone; with each one contributing with one cycle treated with vaginal progesterone supplementation or placebo as a reference (group B). Endometrial thickness, circulating progesterone levels, and endometrial histology were also documented in all cycles. RNA-seq was used to identify genes whose transcript levels significantly changed by the administration of progesterone versus placebo, with postovulatory administration of mifepristone. The transcript profiles of these genes were further evaluated in the endometrial samples from group B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 43 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •proven fertility
- •regular menstrual cycles
- •surgically sterilized at least one year before participating in the protocol
排除标准
- •chronic medical problems
- •abnormal results of screening blood tests
- •ovarian masses
- •symptomatic endometriosis
- •uterine leiomyomata
- •being under chronic medication or taking hormones or drugs able to modify the metabolism of steroid hormones in the 3 preceding months to study enrollment
研究组 & 干预措施
Mife + PLA
Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal placebo during LH+3 until LH+5
干预措施: mifepristone 200 mg (Drug)
Mife + PLA
Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal placebo during LH+3 until LH+5
干预措施: Placebo Vaginal (Drug)
Mife + P4
Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
干预措施: Micronized Progesterone 600 mg (Drug)
Mife + P4
Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
干预措施: mifepristone 200 mg (Drug)
PLA + P4
An oral placebo pill two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
干预措施: Micronized Progesterone 600 mg (Drug)
PLA + P4
An oral placebo pill two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
干预措施: Oral Placebo Tablet (Drug)
PLA + PLA
An oral placebo pill two days after positive LH (LH+2) and a vaginal placebo during LH+3 until LH+5
干预措施: Oral Placebo Tablet (Drug)
PLA + PLA
An oral placebo pill two days after positive LH (LH+2) and a vaginal placebo during LH+3 until LH+5
干预措施: Placebo Vaginal (Drug)
结局指标
主要结局
Endometrial Gene Expression Profile
时间窗: From enrollment to the end of treatments after aproximately 12 weeks
RNA-seq gene expression in the midluteal phase
次要结局
- Endometrial dating(From enrollment to the end of treatments after aproximately 8 months)