Clinical Trials Evaluating the Effect of Metformin Treatment on Function Endometrium in Women Diagnosed With Idiopathic Infertility (METIN)

A Randomized, Controlled, Double-blind Study Clinical Trials Evaluating the Effect of Metformin Treatment on Function Endometrium in Women Diagnosed With Idiopathic Infertility

Randomized, controlled, double-blind, three-arm clinical trial in which 75 women will be randomized to treatment with metformin, 75 women to treatment with placebo and 50 women to the observation group. The medical intervention will last 24 weeks (6 months). Women with confirmed idiopathic infertility, in whom infertility factors have been excluded during full diagnostics, will be included in the study

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Metformin Hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Monika Zbucka-Krętowska, Associate Professor; Phone Number: +48 85 831 87 89; Email: monika.zbucka-kretowska@umb.edu.pl
• Study Contact Backup: Name: Clinical Research Support Center; Phone Number: +48 85 686 53 86; Email: owbk@umb.edu.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 18-45
2. No pregnancy for a minimum of 12 months prior to screening.
3. Diagnosed with idiopathic infertility.
4. No use of hormone therapy 30 days before screening.
5. No use of any methods of contraception 30 days before screening and during the examination.
6. BMI between 18.5 - 30 kg/m2.

Exclusion Criteria:

1. Positive pregnancy test result.
2. Patients diagnosed with another factor of infertility.
3. Patients with type I or II diabetes.
4. Patients taking metformin or other hypoglycaemic drugs in the last 4 weeks before screening.
5. Patients with hepatic impairment and abnormal liver function tests (alanine aminotransferase and/or aspartate aminotransferase (above 3x ULN).
6. Patients with an eGFR less than 45 mL/min/1.73m2.
7. Accompanying chronic diseases with poor prognosis.
8. Patients with a history of lactic acidosis or other metabolic acidosis.
9. Patients with a history of congestive heart failure III/IV NYHA degree.
10. Patients with acute myocardial ischemia.
11. Patients with sepsis or severe infection.
12. Diseases which, in the opinion of the investigator, constitute an exclusion criterion and prevent the patient from participating in the study.
13. Patients with predictable problems with cooperation with the research team.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metformin; patients randomized to received metformin	Drug: Metformin Hydrochloride; The investigational medicinal product/placebo will be dispensed to study participants by study staff during randomization visits V1, V2, V3, V4, V5 and V6. The randomized patient will receive the investigational medicinal product/placebo in tablets of 500 mg. The received tablets will be dispensed in an amount sufficient for the next visit. Patients will be asked to bring unused medicine and all empty ones packaging to the Center for each subsequent visit. The investigational medicinal product/placebo will be administered orally 500 mg three times a day (Table No. 1). The dose of the study product will be gradually increased from 500 mg/day to 1500 mg/day in order to avoid or reduce side effects related to taking the study medicinal product metformin
Placebo Comparator: placebo; patients randomized to received placebo	Drug: Placebo; The investigational medicinal product/placebo will be dispensed to study participants by study staff during randomization visits V1, V2, V3, V4, V5 and V6. The randomized patient will receive the investigational medicinal product/placebo in tablets of 500 mg. The received tablets will be dispensed in an amount sufficient for the next visit. Patients will be asked to bring unused medicine and all empty ones packaging to the Center for each subsequent visit. The investigational medicinal product/placebo will be administered orally 500 mg three times a day (Table No. 1). The dose of the study product will be gradually increased from 500 mg/day to 1500 mg/day in order to avoid or reduce side effects related to taking the study medicinal product metformin
No Intervention: group without intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of metformin on fertility and the possibility of becoming pregnant,as measured by pregnancy test strips and β-hCG levels	The aim of the study is to evaluate the effect of metformin on endometrial function in women diagnosed with idiopathic infertility, by proving the use of the proposed therapy to improve fertility in these women.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the effect of metformin therapy on endometrial function.	It will be tested by assessing the concentration of biomarkers in the tissue before and after treatment	4 years
Molecular analysis of endometrial tissues using Next Generation Sequencing (NGS) technology	Transcriptome analysis of endometrial tissues before and after metformin therapy.	4 years
Intra-tissue metabolic profiling of steroids	The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium.	4 years
Oxidative stress evaluation by using total oxidative capacity (TOC) and total antioxidant capacity (TAC)	In-depth analysis of molecular and cellular processes using multi-omics combined with clinical data will provide essential knowledge about the mechanisms of metformin's action, which may have clinical applications not only in cases of idiopathic female infertility but also in other disorders.	4 years
Quality of Life questionary evaluation SF-36, FertiQoL,	The results on the response scales are rotatable, summed and scaled from 0 to 100. Subscale and higher scores indicate good quality life. The number of obtained equation points is 50 or less arrangements with a psychologist.	24 weeks

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Collaborators: Medical Research Agency, Poland

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: August 22, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 2021/ABM/03/00006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No