xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06012682</url>
    </required_header>
    <id_info>
      <org_study_id>2021/ABM/03/00006</org_study_id>
      <nct_id>NCT06012682</nct_id>
    </id_info>
    <brief_title>Clinical Trials Evaluating the Effect of Metformin Treatment on Function Endometrium in Women Diagnosed With Idiopathic Infertility</brief_title>
    <acronym>METIN</acronym>
    <official_title>A Randomized, Controlled, Double-blind Study Clinical Trials Evaluating the Effect of Metformin Treatment on Function Endometrium in Women Diagnosed With Idiopathic Infertility</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medical University of Bialystok</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Medical Research Agency, Poland</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Medical University of Bialystok</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Randomized, controlled, double-blind, three-arm clinical trial in which 75 women will be&#xD;
        randomized to treatment with metformin, 75 women to treatment with placebo and 50 women to&#xD;
        the observation group. The medical intervention will last 24 weeks (6 months). Women with&#xD;
        confirmed idiopathic infertility, in whom infertility factors have been excluded during full&#xD;
        diagnostics, will be included in the study&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Effects of metformin on fertility and the possibility of becoming pregnant,as measured by pregnancy test strips and β-hCG levels</measure>
      <time_frame>4 years</time_frame>
      <description>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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Evaluation of the effect of metformin therapy on endometrial function.</measure>
      <time_frame>4 years</time_frame>
      <description>It will be tested by assessing the concentration of biomarkers in the tissue before and after treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Molecular analysis of endometrial tissues using Next Generation Sequencing (NGS) technology</measure>
      <time_frame>4 years</time_frame>
      <description>Transcriptome analysis of endometrial tissues before and after metformin therapy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intra-tissue metabolic profiling of steroids</measure>
      <time_frame>4 years</time_frame>
      <description>The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Oxidative stress evaluation by using total oxidative capacity (TOC) and total antioxidant capacity (TAC)</measure>
      <time_frame>4 years</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life questionary evaluation SF-36, FertiQoL,</measure>
      <time_frame>24 weeks</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Infertility, Female</condition>
    <arm_group>
      <arm_group_label>metformin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>patients randomized to received metformin</description>
    </arm_group>
    <arm_group>
      <arm_group_label>placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>patients randomized to received placebo</description>
    </arm_group>
    <arm_group>
      <arm_group_label>group without intervention</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Metformin Hydrochloride</intervention_name>
      <description>The investigational medicinal product/placebo will be dispensed to study participants by study staff during randomization visits V1, V2, V3, V4, V5 and V6.&#xD;
  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</description>
      <arm_group_label>metformin</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>The investigational medicinal product/placebo will be dispensed to study participants by study staff during randomization visits V1, V2, V3, V4, V5 and V6.&#xD;
  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</description>
      <arm_group_label>placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 18-45&#xD;
  &#xD;
            2. No pregnancy for a minimum of 12 months prior to screening.&#xD;
  &#xD;
            3. Diagnosed with idiopathic infertility.&#xD;
  &#xD;
            4. No use of hormone therapy 30 days before screening.&#xD;
  &#xD;
            5. No use of any methods of contraception 30 days before screening and during the&#xD;
               examination.&#xD;
  &#xD;
            6. BMI between 18.5 - 30 kg/m2.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Positive pregnancy test result.&#xD;
  &#xD;
            2. Patients diagnosed with another factor of infertility.&#xD;
  &#xD;
            3. Patients with type I or II diabetes.&#xD;
  &#xD;
            4. Patients taking metformin or other hypoglycaemic drugs in the last 4 weeks before&#xD;
               screening.&#xD;
  &#xD;
            5. Patients with hepatic impairment and abnormal liver function tests (alanine&#xD;
               aminotransferase and/or aspartate aminotransferase (above 3x ULN).&#xD;
  &#xD;
            6. Patients with an eGFR less than 45 mL/min/1.73m2.&#xD;
  &#xD;
            7. Accompanying chronic diseases with poor prognosis.&#xD;
  &#xD;
            8. Patients with a history of lactic acidosis or other metabolic acidosis.&#xD;
  &#xD;
            9. Patients with a history of congestive heart failure III/IV NYHA degree.&#xD;
  &#xD;
           10. Patients with acute myocardial ischemia.&#xD;
  &#xD;
           11. Patients with sepsis or severe infection.&#xD;
  &#xD;
           12. Diseases which, in the opinion of the investigator, constitute an exclusion criterion&#xD;
               and prevent the patient from participating in the study.&#xD;
  &#xD;
           13. Patients with predictable problems with cooperation with the research team.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Monika Zbucka-Krętowska, Associate Professor</last_name>
      <phone>+48 85 831 87 89</phone>
      <email>monika.zbucka-kretowska@umb.edu.pl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Clinical Research Support Center</last_name>
      <phone>+48 85 686 53 86</phone>
      <email>owbk@umb.edu.pl</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infertility</mesh_term>
      <mesh_term>Infertility, Female</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metformin</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06012682
  org study id: 2021/ABM/03/00006
  nct id: NCT06012682
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  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
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Effects of metformin on fertility and the possibility of becoming pregnant,as measured by pregnancy test strips and β-hCG levels
  time frame: 4 years
  description: 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.
  measure: Evaluation of the effect of metformin therapy on endometrial function.
  time frame: 4 years
  description: It will be tested by assessing the concentration of biomarkers in the tissue before and after treatment
  measure: Molecular analysis of endometrial tissues using Next Generation Sequencing (NGS) technology
  time frame: 4 years
  description: Transcriptome analysis of endometrial tissues before and after metformin therapy.
  measure: Intra-tissue metabolic profiling of steroids
  time frame: 4 years
  description: The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium.
  measure: Oxidative stress evaluation by using total oxidative capacity (TOC) and total antioxidant capacity (TAC)
  time frame: 4 years
  description: 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.
  measure: Quality of Life questionary evaluation SF-36, FertiQoL,
  time frame: 24 weeks
  description: 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.
  arm group label: metformin
  arm group type: Experimental
  description: patients randomized to received metformin
  arm group label: placebo
  arm group type: Placebo Comparator
  description: patients randomized to received placebo
  arm group label: group without intervention
  arm group type: No Intervention
  intervention type: Drug
  intervention name: Metformin Hydrochloride
  description: 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
  arm group label: metformin
  intervention type: Drug
  intervention name: Placebo
  description: 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
  arm group label: placebo
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Monika Zbucka-Krętowska, Associate Professor
  phone: +48 85 831 87 89
  email: monika.zbucka-kretowska@umb.edu.pl
  last name: Clinical Research Support Center
  phone: +48 85 686 53 86
  email: owbk@umb.edu.pl
  responsible party type: Sponsor
  mesh term: Infertility
  mesh term: Infertility, Female
  mesh term: Metformin