Research OutSmarts Endometriosis II Study

Study Overview
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Brief Summary
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This product will be used as a diagnostic test to screen for the likelihood of endometriosis in menstruating adults with symptoms suggestive of endometriosis. The purpose of the test will be to guide clinical decisions regarding: 1) whether to undergo diagnostic laparoscopy to confirm the presence of endometriosis (currently, the gold standard for diagnosing endometriosis) and/or 2) how to guide the choice of hormonal or other therapies to treat symptoms of endometriosis.

Detailed Description
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Endometriosis is a chronic, complex, and common gynecologic disorder characterized by the growth of endometrial-like tissues outside of the uterus that is accompanied by inflammation. One of the most frustrating problems for those with endometriosis is the long delay before being diagnosed, which can be up to 7-10 years. One of the reasons for this delay is that definitive diagnosis requires invasive surgery (Tomassetti et al, 2021 PMID: 34690084). There are no approved non-invasive methods for predicting endometriosis. This study will assess the analysis of fresh menstrual blood as a non-invasive predictor of endometriosis. This approach is based on the numerous reports documenting the differences in the endometrium of women with and without endometriosis; this endometrium is shed each month as menstrual blood which can be easily collected and analyzed. Through this prospective, non-interventional pilot study the investigators propose to collect and analyze menstrual blood from healthy controls without chronic symptoms of endometriosis and symptomatic women who have significant and chronic symptoms suggestive of endometriosis and are considered by their healthcare providers to be candidates for diagnostic laparoscopic surgery in the coming months (as part of their standard care). Menstrual blood from controls and symptomatic cases will be analyzed using single cell RNA-sequencing to develop a panel of biomarkers that can be developed into a screening test or diagnostic test for endometriosis. The primary objectives of this study are to confirm the results of our recent single cell RNA sequencing (scRNA-Seq) analysis of menstrual effluent obtained from healthy controls vs. endometriosis (and symptomatic subjects) obtained through IRB 13-376 and to develop a screening/ diagnostic algorithm (menstrual global (MG) score) based on the data to be used to predict endometriosis in symptomatic patients. The secondary objective is to assess the reproducibility of the scRNA-Sequencing data using menstrual blood collected across different menstrual cycles among a subset of controls and/or cases (symptomatic patients). There are no existing commercially available products for the diagnostic analysis of cells or tissues present in menstrual effluent for endometriosis or any other condition. To our knowledge this is no commercially available product for predicting endometriosis using peripheral blood or other biological specimens (other than the analysis of ectopic endometriosis lesions themselves). Currently, definitive diagnosis of endometriosis requires laparoscopic surgery and pathological analysis of the removed ectopic lesions.

Official Title
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ROSE II: Pilot Study to Analyze Menstrual Blood to Predict Endometriosis

Conditions
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Endometriosis

Intervention / Treatment
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* Diagnostic Test: Analysis of menstrual blood to predict endometriosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For All 18 to 40 year old menstruating women (continue to get cycles) More than a light menstrual flow (light flow is soaking less than 1 thin pad or light tampon in 4 hours at peak flow) Willingness to provide two menstrual samples across two separate menstrual cycles. Willingness to provide a DNA sample (obtained via menstrual blood or cheek swab) For Controls: •General Absence of *symptoms suggestive of endometriosis which includes: 1-Chronic pelvic pain 2-Painful menses 3-Pain during intercourse 4-Pain going to the bathroom 5-Abdominal bloating (BUT MUST NOT Include): 6-Report of missed days of work, school, athletic,social and/or other activities due to related pain and discomfort For Symptomatic: Consistently Experiencing chronic symptoms of endometriosis* Without definitive diagnosis Seeking physician evaluation (considered by physician to be a candidate for laproscopic surgery Willingness to provide one of the menstrual samples PRIOR to planned surgery Surgical and pathological confirmation of endo (or NOT) Exclusion Criteria: For All: under age 18 or over 40 years Unable/unwilling to provide a menstrual sample Light menstrual flow (light flow is soaking less than 1 thin pad or light tampon in 4 hours at peak flow) Diagnosed with endometriosis CONTROL: More than 1 symptom of endometriosis* Report of missed days of work, school, athletic, social and/or other activities due to related pain and discomfort Symptomatic: Unable to provide a menstrual sample prior to surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control Participant<br>Having No symptoms of Endo. Provide Menstrual samples. | Diagnostic Test: Analysis of menstrual blood to predict endometriosis<br>* Menstrual blood from controls and symptomatic cases will be analyzed using single cell RNA-sequencing to develop a panel of biomarkers that can be developed into a screening test or diagnostic test for endometriosis.<br>|
| Symptomatic participant<br>Having symptoms of Endo and heading to diagnostic surgery as part of their standard of care (referred). | Diagnostic Test: Analysis of menstrual blood to predict endometriosis<br>* Menstrual blood from controls and symptomatic cases will be analyzed using single cell RNA-sequencing to develop a panel of biomarkers that can be developed into a screening test or diagnostic test for endometriosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ROSE II: Pilot study to analyze menstrual blood to predict endometriosis | The investigators will utilize single cell RNA sequencing analysis of stromal cells and uNK cells in menstrual effluent in order to define cellular and gene expression phenotypes that have been shown to be highly correlated with the presence of endometriosis | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ROSE II: Pilot study to assess the progesterone sensitivity or resistance of cultured endometrial stromal cells | The investigators will assess the response of endometrial stromal cells in menstrual blood to in vitro progesterone exposure using measurements of insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnosis