Endometrial Transcript Profile with Progesterone After Post-ovulatory Mifepristone

NCT ID: NCT06616077

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-07
• Study Completion Date: 2023-05-08

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.

Conditions

Endometrial Endocrine Regulation; Progesterone Supplementation in Women After Mifepristone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Mife + PLA

Oral mifepristone 200 mg two days after positive LH (LH+2) and vaginal placebo during LH+3 until LH+5

Group Type: PLACEBO_COMPARATOR

mifepristone 200 mg

Intervention Type: DRUG

Post ovulatory single oral administration (LH+2, LH peak=LH+0)

Placebo Vaginal

Intervention Type: DRUG

Cocoa butter

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

Group Type: EXPERIMENTAL

Micronized Progesterone 600 mg

Intervention Type: DRUG

Vaginal supplementary micronized progesterone will be given after postovulatory administration of the progesterone receptor antagonist mifepristone. Administration from LH+3 to LH+5 (LH peak=LH+0); 200 mg 3 times per day.

mifepristone 200 mg

Intervention Type: DRUG

Post ovulatory single oral administration (LH+2, LH peak=LH+0)

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

Group Type: ACTIVE_COMPARATOR

Micronized Progesterone 600 mg

Intervention Type: DRUG

Vaginal supplementary micronized progesterone will be given after postovulatory administration of the progesterone receptor antagonist mifepristone. Administration from LH+3 to LH+5 (LH peak=LH+0); 200 mg 3 times per day.

Oral Placebo Tablet

Intervention Type: DRUG

Oral placebo tablet containing brewer yeast, cellulose, stearic acid, silica, magnesium stearate

PLA + PLA

An oral placebo pill two days after positive LH (LH+2) and a vaginal placebo during LH+3 until LH+5

Group Type: PLACEBO_COMPARATOR

Oral Placebo Tablet

Intervention Type: DRUG

Oral placebo tablet containing brewer yeast, cellulose, stearic acid, silica, magnesium stearate

Placebo Vaginal

Intervention Type: DRUG

Cocoa butter

Interventions

Micronized Progesterone 600 mg

Vaginal supplementary micronized progesterone will be given after postovulatory administration of the progesterone receptor antagonist mifepristone. Administration from LH+3 to LH+5 (LH peak=LH+0); 200 mg 3 times per day.

Intervention Type: DRUG

mifepristone 200 mg

Post ovulatory single oral administration (LH+2, LH peak=LH+0)

Intervention Type: DRUG

Oral Placebo Tablet

Oral placebo tablet containing brewer yeast, cellulose, stearic acid, silica, magnesium stearate

Intervention Type: DRUG

Placebo Vaginal

Cocoa butter

Intervention Type: DRUG

Other Intervention Names

Progendo; MIFEAPROFA

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 43 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Reproductive Health Research Insritute, Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alejandro A Tapia-Pizarro, Biologist, PhD

Role: STUDY_DIRECTOR

University of Chile

Locations

Hospital San Borja Arriarán

Santiago, Santiago Metropolitan, Chile

Countries

Chile

Other Identifiers

RU001

Identifier Type: -

Identifier Source: org_study_id