Randomized, controlled, double-blind clinical trial evaluating the effect of METformin treatment on endometrial function in women diagnosed with Idiopathic Infertility

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Bialystok

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

16 Oct 2024 → ongoing

Decision date (initial)

2024-12-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-518670-13-00

EudraCT number

2022-003879-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

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.

Secondary objectives 5

1. Evaluation of the effect of metformin therapy on endometrial function. It will be tested by assessing the concentration of markers such as: cytokines, IGF, LIF, TGF-α, EGF, HB-EGF, VEGF, histamine, inhibin B, relaxin and insulin receptor in the tissue before and after treatment.
2. Transcriptome analysis of endometrial tissues (NGS) before and after metformin therapy.
3. Intratissue metabolomic profiling of steroids. The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium.
4. Effect of metformin treatment on the regulation of oxidative stress in the endometrium.
5. Additional information will also be provided by the analysis of the Quality of life (QoL) questionnaire of the patients undergoing the study and the analysis of menus combined with the DXA study.

Conditions and MedDRA coding

idiopathic infertility

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥20≤40.
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.
7. Eligibility for the in vitro fertilization program.

Exclusion criteria 13

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Obtaining a pregnancy during the study.

Secondary endpoints 5

1. Evaluation of the effect of metformin therapy on endometrial function,assessed indirectly by blood tests of patients, will be examined by analyzing the concentrations of markers: cytokine(interleukin 1 and 2),insulin-like growth factor(IGF),leukemia inhibitory factor(LIF),transforming growth factor alpha(TGF-α),epidermal growth factor(EGF),heparin-binding growth factor-like EGF(HB-EGF),vascular endothelial growth factor(VEGF),histamine, inhibin B,relaxin and insulin receptor
2. Analysis of the transcriptome of endometrial tissues using next-generation sequencing (NGS) technology to assess the effectiveness of increasing pregnancy rates in the in vitro fertilization procedure. The study will examine the full transcriptome, including a detailed microRNA profile. This will allow us to assess whether microRNAs, as regulators of gene expression, can act as predictive markers indicating the effectiveness of the in vitro fertilization procedure.
3. Intrauterine metabolomic profiling of steroids will be conducted to investigate whether metabolic analysis of these compounds can be used to identify potential prognostic markers. These markers could then be used to assess the effectiveness of increasing pregnancy rates in an in vitro fertilization procedure.
4. Effect of metformin treatment on regulation of oxidative stress. Increased production of reactive oxygen species (ROS) can negatively affect the implantation process. Metformin stimulates antioxidant processes and reduces the synthesis of ROS, which may contribute to the chance of embryo implantation in in vitro fertilization.
5. Analysis of the Quality of Life (QoL) questionnaire of patients undergoing the study and analysis of menus combined with DXA examination will provide key information to assess the impact of diet and lifestyle on the effectiveness of in vitro fertilization. The data collected will allow a holistic assessment of patients' health and well-being, which can have important implications for the effectiveness of treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Bialystok

Sponsor organisation

Medical University Of Bialystok

Address

Ul. Jana Kilinskiego 1

City

Bialystok

Postcode

15-089

Country

Poland

Scientific contact point

Organisation

Medical University Of Bialystok

Contact name

Reproductive Health Outpatient Clinic

Public contact point

Organisation

Medical University Of Bialystok

Contact name

Reproductive Health Outpatient Clinic

Third parties 2

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications