Clinical trial NCT05601596: Research OutSmarts Endometriosis II Study
Official title: ROSE II: Pilot Study to Analyze Menstrual Blood to Predict Endometriosis
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Endometriosis
Keywords: Diagnosis
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2022-11-01
Enrollment: 185
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The cohort will enroll a total of 185 menstruating individuals in total; 80 control subjects who self-report the general absence of symptoms of endometriosis and 105 symptomatic cases who report chronic symptoms\* of endometriosis but who have not yet been diagnosed and are seeking physician evaluation for their symptoms.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: ROSE II: Pilot study to analyze menstrual blood to predict endometriosis
timeFrame: 2 years
Secondary outcomes:
measure: ROSE II: Pilot study to assess the progesterone sensitivity or resistance of cultured endometrial stromal cells
timeFrame: 2 years
Other outcomes:
Locations:
city: Manhasset
country: United States
facility: Feinstein Institutes/Northwell health
state: New York
Study officials:
affiliation: Northwell Health
name: Peter K Gregersen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwell Health
name: Christine N Metz, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aghajanova L, Giudice LC. Molecular evidence for differences in endometrium in severe versus mild endometriosis. Reprod Sci. 2011 Mar;18(3):229-51. doi: 10.1177/1933719110386241. Epub 2010 Nov 9.
citation: Ballard K, Lowton K, Wright J. What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006 Nov;86(5):1296-301. doi: 10.1016/j.fertnstert.2006.04.054.
citation: Brosens I, Brosens JJ, Benagiano G. The eutopic endometrium in endometriosis: are the changes of clinical significance? Reprod Biomed Online. 2012 May;24(5):496-502. doi: 10.1016/j.rbmo.2012.01.022. Epub 2012 Jan 31.
citation: Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, Innes J, Julie Kim J. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006 Mar 27;248(1-2):94-103. doi: 10.1016/j.mce.2005.11.041. Epub 2006 Jan 10.
citation: Chehna-Patel N, Sachdeva G, Gajbhiye R, Warty N, Khole V. "Spot"-ting differences between the ectopic and eutopic endometrium of endometriosis patients. Fertil Steril. 2010 Nov;94(6):1964-71, 1971.e1. doi: 10.1016/j.fertnstert.2010.01.048. Epub 2010 Mar 16.
citation: Drury JA, Parkin KL, Coyne L, Giuliani E, Fazleabas AT, Hapangama DK. The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis. Reprod Biol Endocrinol. 2018 Jul 18;16(1):67. doi: 10.1186/s12958-018-0385-3.
citation: Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29(3):400-12. doi: 10.1093/humrep/det457. Epub 2014 Jan 15.
citation: Johnston JL, Reid H, Hunter D. Diagnosing endometriosis in primary care: clinical update. Br J Gen Pract. 2015 Feb;65(631):101-2. doi: 10.3399/bjgp15X683665. No abstract available.
citation: International working group of AAGL, ESGE, ESHRE and WES; Tomassetti C, Johnson NP, Petrozza J, Abrao MS, Einarsson JI, Horne AW, Lee TTM, Missmer S, Vermeulen N, Zondervan KT, Grimbizis G, De Wilde RL. An International Terminology for Endometriosis, 2021. J Minim Invasive Gynecol. 2021 Nov;28(11):1849-1859. doi: 10.1016/j.jmig.2021.08.032. Epub 2021 Oct 21.