Clinical trial NCT01301885: ENDOMET - Novel Diagnostic Tools and Treatments for Endometriosis
Official title: Novel Diagnostic Tools for Endometriosis and Their Exploitation for Prognosis and Prevention of Complications
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Endometriosis
Keywords: endometriosis
dysmenorrhea
infertility
biomarker
drug target
recurrence
complications
dyspareunia
dyschezia
dysuria
chronic pelvic pain
surgical treatment
long-term follow-up
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: University of Turku
name: The Finnish Funding Agency for Technology and Innovation (TEKES)
name: VTT Technical Research Centre of Finland
name: Finnish Medical Foundation
name: Hormos Medical
name: PerkinElmer, Wallac Oy
name: Biotop Oy
name: Pharmatest Services Ltd
name: Drug Discovery Graduate School, Finland
name: The National Graduate School of Clinical Investigation, Finland
First posted: 2011-02-23
Enrollment: 230
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Endometriosis: Finnish Caucasian women surgically treated for endometriosis; age 19-48, no significant other disease or medication for other diseases

Healthy controls: symptomless Finnish Caucasian women going through laparoscopy for tubal ligation; age 32-48, no significant other disease or medication

Brief summary: Endometriosis is a chronic disease characterized by the presence of functional endometrial glands and stroma in ectopic locations outside the uterine cavity. The ectopic endometrial tissue responds to estradiol and other hormones similarly to the normal endometrium. Endometriosis is one of the most common benign gynecological conditions, as many as 5-10% of women in the reproductive age may be affected. In addition to pain which may be severe, subfertility is one of the typical problems associated with endometriosis and may be present in up to 40% of those affected. There is lack of a clear correlation between severity of pain and degree of compromised fertility. Different modes of treatment exist. Hormonal treatments are based on the suppression of estrogenic action on endometriosis as well as the endometrium. Unfortunately, discontinuation of the hormonal treatment typically results in a rapid recurrence of the disease. Surgery may alleviate the symptom for different lengths of time, however, curative treatment frequently involves hysterectomy with bilateral oophorectomy. In order to escape this radical treatment, new targeted therapy in the form of novel pharmacological agents would be of crucial importance. Presently, endometriosis can be reliably diagnosed only by laparoscopy. Since this is an invasive surgical procedure, new diagnostic tools would be warmly welcomed. Furthermore, as the progression of the disease is presently impossible to predict, new markers for the "malignancy" of each case are desperately needed.

The aim of the investigators research is to identify expression of endometriosis specific RNAs/proteins. Evaluation of expression profiles in samples of endometriosis and endometrium of patients with careful clinical and surgical classification of endometriosis as well as healthy control women should initially enable to identify novel targets for new therapies and biomarkers. Particularly the different pain symptoms will be recorded annually and evaluated comprehensively. Furthermore, combined with an adequate 10-year follow up (based on a questionnaire, including fertility, received treatments and different pain symptoms; NRS), the study should enable for example to identify markers for endometriosis associated infertility as well as cases where the disease progresses very rapidly or reoccurs. Different forms of effective treatment may thereafter be designed following the identification of such factors.


Eligibility criteria: Inclusion Criteria:

* study group: surgically and pathologically verified endometriosis
* control group: existence of endometriosis ruled out in laparoscopy

Exclusion Criteria:

* no other significant disease or medication for other diseases
* suspicion of malignancy
* pregnancy
* acute infection
* insufficient understanding of Finnish language
* previous hysterectomy and/or bilateral salpingo-oophorectomy

Primary outcomes:
measure: Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions.
timeFrame: During the surgical sample collection
measure: Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels.
timeFrame: During the surgical sample collection
measure: Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts.
timeFrame: During the surgical sample collection
measure: A relational database to identify differentially expressed genes in the endometrium and endometriosis lesions
timeFrame: During the surgical sample collection
Secondary outcomes:
measure: A prospective 5-year follow-up of pain recurrence after surgical treatment of endometriosis
timeFrame: 5 years (annually) after the completion of patient recruitment
measure: Serum HE-4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women
timeFrame: During surgical sample collection
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Dept of Obstetrics and Gynecology, Helsinki University Hospital
city: Joensuu
country: Finland
facility: Dept of Obstetrics and Gynecology, North Carelia Central Hospital
city: Lahti
country: Finland
facility: Dept of Obstetrics and Gynecology, Päijät-Häme Central Hospital
city: Turku
country: Finland
facility: Dept of Obstetrics and Gynecology, Turku University Central Hospital
Study officials:
affiliation: Department of Obstetrics and Gynecology, Turku University Central Hospital
name: Antti Perheentupa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gabriel M, Fey V, Heinosalo T, Adhikari P, Rytkonen K, Komulainen T, Huhtinen K, Laajala TD, Siitari H, Virkki A, Suvitie P, Kujari H, Aittokallio T, Perheentupa A, Poutanen M. A relational database to identify differentially expressed genes in the endometrium and endometriosis lesions. Sci Data. 2020 Aug 28;7(1):284. doi: 10.1038/s41597-020-00623-x.
citation: Heinosalo T, Gabriel M, Kallio L, Adhikari P, Huhtinen K, Laajala TD, Kaikkonen E, Mehmood A, Suvitie P, Kujari H, Aittokallio T, Perheentupa A, Poutanen M. Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis. Hum Reprod. 2018 May 1;33(5):817-831. doi: 10.1093/humrep/dey026.
citation: Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setala M, Harkki P, Jalkanen J, Fraser J, Makinen J, Auranen A, Poutanen M, Perheentupa A. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009 Apr 21;100(8):1315-9. doi: 10.1038/sj.bjc.6605011. Epub 2009 Mar 31.
citation: Hiissa J, Elo LL, Huhtinen K, Perheentupa A, Poutanen M, Aittokallio T. Resampling reveals sample-level differential expression in clinical genome-wide studies. OMICS. 2009 Oct;13(5):381-96. doi: 10.1089/omi.2009.0027.
citation: Hallamaa M, Suvitie P, Huhtinen K, Matomaki J, Poutanen M, Perheentupa A. Serum HE4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women. Gynecol Oncol. 2012 Jun;125(3):667-72. doi: 10.1016/j.ygyno.2012.03.011. Epub 2012 Mar 14.
citation: Huhtinen K, Desai R, Stahle M, Salminen A, Handelsman DJ, Perheentupa A, Poutanen M. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab. 2012 Nov;97(11):4228-35. doi: 10.1210/jc.2012-1154. Epub 2012 Sep 11.
citation: Huhtinen K, Saloniemi-Heinonen T, Keski-Rahkonen P, Desai R, Laajala D, Stahle M, Hakkinen MR, Awosanya M, Suvitie P, Kujari H, Aittokallio T, Handelsman DJ, Auriola S, Perheentupa A, Poutanen M. Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions. J Clin Endocrinol Metab. 2014 Nov;99(11):E2188-97. doi: 10.1210/jc.2014-1913. Epub 2014 Aug 19.
citation: Vehmas AP, Muth-Pawlak D, Huhtinen K, Saloniemi-Heinonen T, Jaakkola K, Laajala TD, Kaprio H, Suvitie PA, Aittokallio T, Siitari H, Perheentupa A, Poutanen M, Corthals GL. Ovarian endometriosis signatures established through discovery and directed mass spectrometry analysis. J Proteome Res. 2014 Nov 7;13(11):4983-94. doi: 10.1021/pr500384n. Epub 2014 Aug 20.