Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03756480
Recruitment Status : Not yet recruiting
First Posted : November 28, 2018
Last Update Posted : November 14, 2019
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Johns Hopkins University

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.

Condition or disease
Endometriosis Endometrial Diseases

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.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 135 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Prospective Clinical Study of the Relationship Between Cancer Driving Mutations Found in Endometriotic Implants and the Development of Progesterone Resistance
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis

Group/Cohort
Case Group

Clinical or surgical diagnosis of Endometriosis, patients undergoing surgical management

100 participants

Control Group

No diagnosis of Endometriosis, Patients undergoing Laparoscopic Tubal Ligation

35 participants




Primary Outcome Measures :
  1. Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions. [ Time Frame: Six month ]
    Digital droplet PCR will be used to identify somatic cancer-driver mutations with the presence of at least one of KRAS or ARID1A or PIK3CA or PPP2R1A cancer-driver mutations to assess any difference between progesterone-resistant endometriosis and progesterone-sensitive endometriosis.


Secondary Outcome Measures :
  1. Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects [ Time Frame: Six month ]
    Whole exome sequencing in a subset of patients with progesterone-resistant disease and controls will be done using TruSeq Amplicon Cancer Panel (Illumina) to assess the number of cancer driver mutations.

  2. Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects. [ Time Frame: One month ]
    DNA methylation profile of eutopic and ectopic endometrial tissue for cases and controls will be done using Raw Illumina 450K methylation array to assess for any difference.


Biospecimen Retention:   Samples With DNA
Endometrial tissue from ectopic and eutopic sites and blood sample.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03756480


Contacts
Layout table for location contacts
Contact: James Segars, MD, FACOG 410-614-2000 jsegars2@jhmi.edu
Contact: Bhuchitra Singh, MBBS,MPH,MS 410-955-6771 bsingh10@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21218
Sub-Investigator: Ie Ming Shih, MD, PhD         
Sub-Investigator: Tian-Li Wang, PhD         
Sub-Investigator: Maria Facadio Antero, MD         
Sub-Investigator: Bhuchitra Singh, MBBS,MPH,MS         
Sponsors and Collaborators
Johns Hopkins University
National Institutes of Health (NIH)
Investigators
Layout table for investigator information
Principal Investigator: James Segars, MD, FACOG Professor

Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03756480     History of Changes
Other Study ID Numbers: IRB00188129
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Johns Hopkins University:
Endometriosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Endometriosis
Uterine Diseases
Genital Diseases, Female
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs