Endometrial Transcript Profile with Progesterone After Post-ovulatory Mifepristone

Early Phase 1

Completed

• Conditions: Endometrial Endocrine Regulation; Progesterone Supplementation in Women After Mifepristone
• Interventions: Drug: mifepristone 200 mg; Drug: Micronized Progesterone 600 mg; Drug: Placebo Vaginal; Drug: Oral Placebo Tablet

• Registration Number: NCT06616077
• Lead Sponsor: Reproductive Health Research Insritute, Chile

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2022-06-07
• Primary Completion: 2023-04-27
• Study Completion: 2023-05-08
• Status Verified: 2024-09
• Study First Submitted: 2024-09-17
• Study First Submitted QC: 2024-09-24
• Last Update Submitted: 2024-09-24
• Study First Posted: 2024-09-27
• Last Update Posted: 2024-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 9

Inclusion Criteria

• proven fertility
• regular menstrual cycles
• surgically sterilized at least one year before participating in the protocol

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Mife + PLA	mifepristone 200 mg	Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal placebo during LH+3 until LH+5
Mife + PLA	Placebo Vaginal	Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal placebo during LH+3 until LH+5
Mife + P4	Micronized Progesterone 600 mg	Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
Mife + P4	mifepristone 200 mg	Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
PLA + P4	Micronized Progesterone 600 mg	An oral placebo pill two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
PLA + P4	Oral Placebo Tablet	An oral placebo pill two days after positive LH (LH+2) and vaginal micronized progesterone (600 mg/day) during LH+3 until LH+5
PLA + PLA	Oral Placebo Tablet	An oral placebo pill two days after positive LH (LH+2) and a vaginal placebo during LH+3 until LH+5
PLA + PLA	Placebo Vaginal	An oral placebo pill two days after positive LH (LH+2) and a vaginal placebo during LH+3 until LH+5

Primary Outcome Measures

Name	Time	Method
Endometrial Gene Expression Profile	From enrollment to the end of treatments after aproximately 12 weeks	RNA-seq gene expression in the midluteal phase

Secondary Outcome Measures

Name	Time	Method
Endometrial dating	From enrollment to the end of treatments after aproximately 8 months	Estimated cycle day based on endometrial morphology according to the Noyes criteria

Trial Locations

Locations (1)

Hospital San Borja Arriarán; 🇨🇱 Santiago, Región Metropolitana, Chile