## Protocol Section
### Identification Module
**NCT ID:** NCT06414720

**Acronym:** ENDOmiRNA

**Brief Title:** Salivary microRNA in Endometriosis: Correlation With Response to Progestin Therapy

**Official Title:** Salivary MicroRNA in Endometriosis: Correlation With Progestin Treatment Response: A Prospective Observational Study

#### Organization Study ID Info
**ID:** ENDOmiRNA
#### Organization
**Class:** OTHER
**Full Name:** University of Udine
### Status Module
#### Completion Date
**Date:** 2025-05-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-01-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-04-22

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-05
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Udine

#### Responsible Party

**Investigator Affiliation:** University of Udine

**Investigator Full Name:** Giuseppe Vizzielli

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study aims to analyze the salivary miRNA specific for patients diagnosed with endometriosis, specifically evaluating the miRNA profile of patients who respond versus those who do not respond to progestin therapy. Ninety patients attending the Chronic Pelvic Pain Clinic will be recruited, and they will be asked to provide a saliva sample before starting medical therapy. The response to the therapy will be evaluated after 4 months from the beginning of the therapy itself.

**Detailed Description:** In recent years, scientific literature has focused on the search for new non-invasive diagnostic tools that can identify patients with endometriosis early and easily, thereby reducing diagnostic delay and enabling the immediate initiation of appropriate treatment. Among these, microRNA (miRNA) is emerging as a promising option. Despite recent progress in this field, a predictive biomarker of response to medical therapy or vice versa, resistance to progesterone in endometriosis, has not yet been identified, including among miRNAs. This study aims, therefore, to identify salivary miRNA signatures specific to endometriosis and differentially expressed between responder and non-responder patients to 2 mg dienogest medical therapy. 90 patients diagnosed with endometriosis attending the Obstetrics and Gynecology Clinic at the Santa Maria della Misericordia Hospital in Udine will be enrolled. The investigators will ask them for a salivary sample before starting the progestin therapy. After 4 months from the beginning, the response will be evaluated. The researchers will evaluate the differences between salivary miRNA of the responders vs non-responders.

### Conditions Module

**Conditions:**

- Endometriosis

**Keywords:**

- Endometriosis

- miRNA

- Progesterone resistance

### Design Module

#### Bio Spec

**Description:** salivary specimen

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 90

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients diagnosed with endometriosis attending the Obstetrics and Gynecology Clinic at the Santa Maria della Misericordia Hospital in Udine, who have not yet started medical therapy.

**Intervention Names:**

- Drug: Dienogest 2 MG

**Label:** Endometriosis patients

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Endometriosis patients

**Description:** The patients will be started on progestin therapy after a saliva sample is collected from them for miRNA analysis.

**Name:** Dienogest 2 MG

**Other Names:**

- zafrilla

- devicius

- endodien

- visanne

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** response to 2 mg dienogest therapy evaluated with NRS (numeric rating scale) scale assessed for acyclic pain, dyspareunia, dyschezia, dysmenorrhea, periovulatory pain

**Measure:** response to the progestin therapy

**Time Frame:** 0 (pre-therapy) - 4 months (after therapy)

**Description:** changes in quality of life assessed with questionnaire SF-36 (Short Form Health Survey 36)

**Measure:** changes in quality of life

**Time Frame:** 0 (pre-therapy) - 4 months (after therapy)

**Description:** Once it is established which patients are responders and which are non-responders, differential salivary miRNAs between the two groups will be identified via sequencing. The miRNA reverse transcription reaction will be performed using the reverse transcription kit TaqMan MicroRNA (Applied Biosystems). The reverse transcription product will be used for Real-time PCR. The small nucleolar RNA RNU6 will be used as an endogenous control. The protocol of Amplification will be carried out using the LightCycler 480 instrument (Roche). For each miRNA, qPCR will be performed in duplicate. The relative expression levels of miRNAs will be calculated using the 2-ΔΔCt method.

**Measure:** differences in salivary miRNoma

**Time Frame:** sample collection at time 0, analysis after time 4

### Eligibility Module

**Eligibility Criteria:** INCLUSION CRITERIA

* Age \> 18 years
* Fertile age
* Clinical-ultrasound diagnosis or histological diagnosis of endometriosis
* Informed consent

EXCLUSION CRITERIA

* Pregnancy
* Pre-menarcheal or post-menopausal status
* Chronic pelvic pain syndrome with or without central sensitization assessed with the Central Sensitization Inventory Test (CSI)
* Neoplasia, diabetes, BMI \> 30 kg/m2, coagulopathies, autoimmune diseases, or other conditions that may affect salivary miRNA measurement
* Currently undergoing progestin therapy

**Maximum Age:** 45 Years

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

**Study Population:** All the patients diagnosed with endometriosis attending the Obstetrics and Gynecology Clinic at the Santa Maria della Misericordia Hospital in Udine, who meet the inclusion criteria.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** matildedegano@rocketmail.com

**Name:** Matilde Degano, dr

**Phone:** 3206173076

**Phone Ext:** 0039

**Role:** CONTACT

**Contact 2:**

**Email:** anna.biasioli@asufc.sanita.fvg.it

**Name:** Anna Biasioli, dr

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Udine

**Contacts:**

***Contact 1:***

- **Email:** matildedegano@rocketmail.com

- **Name:** Matilde Degano, dr

- **Phone:** 3206173076

- **Phone Ext:** 0039

- **Role:** CONTACT

***Contact 2:***

- **Email:** anna.biasioli@asufc.sanita.fvg.it

- **Name:** Anna Biasioli, dr

- **Role:** CONTACT

***Contact 3:***

- **Name:** Daniela Cesselli, prof

- **Role:** SUB_INVESTIGATOR

***Contact 4:***

- **Name:** Michela Bulfoni, dr

- **Role:** SUB_INVESTIGATOR

**Country:** Italy

**Facility:** University of Udine

**State:** UD

**Status:** RECRUITING

**Zip:** 33100

#### Overall Officials

**Official 1:**

**Affiliation:** University of Udine

**Name:** Giuseppe Vizzielli, prof

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Bendifallah S, Suisse S, Puchar A, Delbos L, Poilblanc M, Descamps P, Golfier F, Jornea L, Bouteiller D, Touboul C, Dabi Y, Darai E. Salivary MicroRNA Signature for Diagnosis of Endometriosis. J Clin Med. 2022 Jan 26;11(3):612. doi: 10.3390/jcm11030612.

**PMID:** 35160066

**Citation:** Zhang P, Wang G. Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms. Int J Mol Sci. 2023 Apr 10;24(8):6992. doi: 10.3390/ijms24086992.

**PMID:** 37108154

**Citation:** Hon JX, Wahab NA, Karim AKA, Mokhtar NM, Mokhtar MH. MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance. Int J Mol Sci. 2023 Oct 9;24(19):15001. doi: 10.3390/ijms241915001.

**PMID:** 37834449

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005831

- Term: Genital Diseases, Female

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000091662

- Term: Genital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7877

- Name: Endometriosis

- Relevance: HIGH

- As Found: Endometriosis

- ID: M8943

- Name: Genital Diseases, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000004715

- Term: Endometriosis

### Intervention Browse Module - Ancestors

- ID: D000003272

- Term: Contraceptive Agents, Male

- ID: D000003270

- Term: Contraceptive Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000003278

- Term: Contraceptives, Oral, Hormonal

- ID: D000003276

- Term: Contraceptives, Oral

- ID: D000003271

- Term: Contraceptive Agents, Female

- ID: D000080066

- Term: Contraceptive Agents, Hormonal

- ID: D000006727

- Term: Hormone Antagonists

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000018931

- Term: Antineoplastic Agents, Hormonal

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M230930

- Name: Dienogest

- Relevance: HIGH

- As Found: Fidelity

- ID: M14244

- Name: Progestins

- Relevance: LOW

- As Found: Unknown

- ID: M14245

- Name: Progesterone

- Relevance: LOW

- As Found: Unknown

- ID: M6494

- Name: Contraceptive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M6496

- Name: Contraceptive Agents, Male

- Relevance: LOW

- As Found: Unknown

- ID: M6500

- Name: Contraceptives, Oral

- Relevance: LOW

- As Found: Unknown

- ID: M6502

- Name: Contraceptives, Oral, Hormonal

- Relevance: LOW

- As Found: Unknown

- ID: M6495

- Name: Contraceptive Agents, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2116

- Name: Contraceptive Agents, Hormonal

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M20966

- Name: Antineoplastic Agents, Hormonal

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000023635

- Term: Dienogest

### Misc Info Module

- Version Holder: 2024-05-31
