Clinical trial NCT03756480: Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance
Official title: Prospective Clinical Study of the Relationship Between Cancer Driving Mutations Found in Endometriotic Implants and the Development of Progesterone Resistance
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Endometriosis
Endometrial Diseases
Keywords: Endometriosis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-11-28
Enrollment: 135
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Women between the ages of 18-45 undergoing surgical management for endometriosis as cases and women between ages of 18-45 years undergoing elective tubal ligation and no diagnosis of endometriosis.

Brief summary: This study will test the hypothesis that the molecular changes present in ectopic endometriosis lesions correlate with progesterone-resistant disease (using the criteria defined in this study) and are present in matched eutopic endometrium.

Detailed description: Tissues from 100 patients with endometriosis will be analyzed with droplet digital PCR (ddPCR) targeted sequencing and responders (n=50) will be compared to non-responders (n=50) after controlling confounding factors.

From a subset of the 100 cases, whole exome sequencing (WES) and Methylation-Specific PCR (MSP)-based methylation profiling on microdissected epithelium and stroma will be performed in matched eutopic and ectopic tissues from 20 patients with known cancer-associated mutations or 20 controls.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent.
* Gender: female.
* Age: 18-45 years at the time of signing consent.
* Clinical or surgical diagnosis of endometriosis undergoing laparoscopy.
* Controls may not have clinical or surgical diagnosis of endometriosis.
* Regular menstrual cycles.
* BMI between 18-40 kg/m2.
* Sexually active or have had a previous vaginal exam that used a speculum.
* English speaking

Exclusion Criteria:

* Use of any kind of steroidal therapy including oral contraceptives, Norplant, estrogen replacement/supplemental therapy, androgens (Danazol, Cyclomen, Danocrine, testosterone) or progesterone. She may not be taking or be on Celebrex.
* Pregnant.
* Presence of pelvic infection.
* Mullerian anomalies with absence of a cervix.
* History of cancer of the reproductive tract.
* Presence of undiagnosed uterine bleeding.
* Treatment with intrauterine device (IUD) or progestin-containing intrauterine device.

Primary outcomes:
measure: Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions.
timeFrame: Six month
Secondary outcomes:
measure: Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects
timeFrame: Six month
measure: Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects.
timeFrame: One month
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Professor
name: James Segars, MD, FACOG
role: PRINCIPAL_INVESTIGATOR
References: