ENDOMET - Novel Diagnostic Tools and Treatments for Endometriosis

NCT01301885 | Recruiting

• 1 other identifier: ENDOMET-231/2004
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 4

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.

Conditions

Endometriosis

Keywords

endometriosis; dysmenorrhea; infertility; biomarker; drug target; recurrence; complications; dyspareunia; dyschezia; dysuria; chronic pelvic pain; surgical treatment; long-term follow-up

Outcome Measures

Primary Outcomes (4)

• Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions.

  During the surgical sample collection

• Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels.

  During the surgical sample collection

• Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts.

  During the surgical sample collection

• A relational database to identify differentially expressed genes in the endometrium and endometriosis lesions

  During the surgical sample collection

Secondary Outcomes (2)

• A prospective 5-year follow-up of pain recurrence after surgical treatment of endometriosis

  5 years (annually) after the completion of patient recruitment

• Serum HE-4 concentration is not dependent on menstrual cycle or hormonal treatment among endometriosis patients and healthy premenopausal women

  During surgical sample collection

Study Arms (2)

Endometriosis

Women (19-48 years of age) with surgically confirmed endometriosis.

Procedure: Laparoscopy/laparotomy

Healthy women

Healthy women (32-48 years of age), symptom free, existence of endometriosis ruled out during laparoscopy for tubal ligation

Procedure: Laparoscopy/laparotomy

Interventions

Laparoscopy/laparotomy PROCEDURE

Surgical treatment of endometriosis (laparotomy/laparoscopy) or laparoscopic sterilisation. Sample collection in both groups.

Endometriosis; Healthy women

Eligibility Criteria

• Age: 19 Years - 48 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Turku University Hospital: lead
• University of Turku: collaborator
• The Finnish Funding Agency for Technology and Innovation (TEKES): collaborator
• VTT Technical Research Centre of Finland: collaborator
• Finnish Medical Foundation: collaborator
• Hormos Medical: collaborator
• PerkinElmer, Wallac Oy: collaborator
• Biotop Oy: collaborator
• Pharmatest Services Ltd: collaborator
• Drug Discovery Graduate School, Finland: collaborator
• The National Graduate School of Clinical Investigation, Finland: collaborator

Study Sites (4)

Dept of Obstetrics and Gynecology, Helsinki University Hospital

Helsinki, 00029, Finland

COMPLETED

Dept of Obstetrics and Gynecology, North Carelia Central Hospital

Joensuu, 80210, Finland

COMPLETED

Dept of Obstetrics and Gynecology, Päijät-Häme Central Hospital

Lahti, 15850, Finland

COMPLETED

Dept of Obstetrics and Gynecology, Turku University Central Hospital

Turku, 20520, Finland

RECRUITING

Related Publications (8)

• 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.

  PMID: 32859947 BACKGROUND

• 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.

  PMID: 29462326 BACKGROUND

• 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.

  PMID: 19337252 RESULT

• 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.

  PMID: 19663710 RESULT

• 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.

  PMID: 22426487 RESULT

• 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.

  PMID: 22969138 RESULT

• 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.

  PMID: 25137424 RESULT

• 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.

  PMID: 25099244 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

serum, peritoneal fluid, endometrium tissue, healthy peritoneum, tissue of endometriosis (peritoneal, ovarian, deep infiltrating. Extracted DNA, RNA, cDNA and protein from the above samples.

MeSH Terms

Conditions

Endometriosis; Dysmenorrhea; Infertility; Recurrence; Dyspareunia; Constipation; Dysuria

Interventions

Laparoscopy; Laparotomy

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Disease Attributes; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders; Signs and Symptoms, Digestive; Lower Urinary Tract Symptoms; Urological Manifestations

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Antti Perheentupa, MD, PhD

  Department of Obstetrics and Gynecology, Turku University Central Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antti H Perheentupa, MD PhD

CONTACT

+358-2-3130000; [email protected]

Kaisa Huhtinen, PhD

CONTACT

+358-2-333 7376; [email protected]

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 21, 2011
• First Posted: February 23, 2011
• Study Start: October 1, 2005
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 16, 2021

Record last verified: 2021-08

Locations

FI (4)