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/NCT05966792</url>
    </required_header>
    <id_info>
      <org_study_id>SGLT2i NLRP3 PCOS</org_study_id>
      <nct_id>NCT05966792</nct_id>
    </id_info>
    <brief_title>SGLT2 Inhibitors in Treating Patients With PCOS</brief_title>
    <official_title>The Clinical Efficacy and Mechanism of SGLT2 Inhibitors Treating Polycystic Ovary Syndrome by Modulating the Nod-like Receptor Protein 3 Inflammasome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai 10th People's Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai 10th People's Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Chronic inflammation is the core of Polycystic ovary syndrome (PCOS), and obesity and&#xD;
        overweight further exacerbate the level of inflammation in the peripheral circulation and&#xD;
        ovarian tissue in PCOS patients. Metformin is a classic endocrine drug for the treatment of&#xD;
        PCOS, but its clinical response rate is only about 40%. Our previous published study&#xD;
        (Diabetes Obes Metab, 2022) observed that the new hypoglycemic drug SGLT-2 inhibitor can&#xD;
        significantly improve the clinical symptoms of patients with insulin resistance PCOS, and the&#xD;
        clinical efficacy is not inferior to metformin, but its specific mechanism of action is not&#xD;
        clear. Recent studies have shown that SGLT-2 significantly attenuates the activation of the&#xD;
        Nod-like receptor protein 3 (NLRP3) inflammasomes and the secretion of IL-1β in patients with&#xD;
        type 2 diabetes mellitus at high risk of cardiovascular disease. Based on the above research&#xD;
        background, this project will combine clinical research and mechanism exploration to solve&#xD;
        the following two problems:&#xD;
  &#xD;
          1. whether metformin plus SGLT2 inhibitor can further improve the clinical efficacy of PCOS&#xD;
             patients compared to metformin plus placebo;&#xD;
  &#xD;
          2. mechanistic studies further clarify whether SGLT2 inhibitors improve inflammatory&#xD;
             symptoms by modulating NLRP3 inflammosomes in the treatment of polycystic ovary&#xD;
             syndrome;&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This clinical study is a prospective, single-center, randomized (1:1) controlled clinical&#xD;
        study. The enrollment population is overweight or obese PCOS patients. After signing the&#xD;
        informed consent form, patients who meet the inclusion/exclusion criteria will be randomly&#xD;
        assigned to the experimental and control groups for treatment in a 1:1 ratio, for a total of&#xD;
        72 patients enrolled.&#xD;
  &#xD;
        Subjects randomized to the trial group will receive SGLT-2 inhibitors plus metformin for 12&#xD;
        weeks.&#xD;
  &#xD;
        Participants randomised to control will receive placebo plus metformin for 12 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">March 15, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 15, 2024</primary_completion_date>
    <phase>Phase 4</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>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>HOMA-IR</measure>
      <time_frame>3 months</time_frame>
      <description>Homeostatic model assessment insulin resistance index</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Menstrual cycles</measure>
      <time_frame>3 months</time_frame>
      <description>annual number of menstrual cycles</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NLRP3</measure>
      <time_frame>3 months</time_frame>
      <description>Nod-like receptor protein 3</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IL-1β</measure>
      <time_frame>3 months</time_frame>
      <description>Interleukin-1 beta</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IL-18</measure>
      <time_frame>3 months</time_frame>
      <description>Interleukin-18</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>LH</measure>
      <time_frame>3 months</time_frame>
      <description>luteinizing hormone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>FSH</measure>
      <time_frame>3 months</time_frame>
      <description>follicle-stimulating hormone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PRL</measure>
      <time_frame>3 months</time_frame>
      <description>prolactin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>E2</measure>
      <time_frame>3 months</time_frame>
      <description>estradiol</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>P</measure>
      <time_frame>3 months</time_frame>
      <description>progesterone</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TT</measure>
      <time_frame>3 months</time_frame>
      <description>total testosterone</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">72</enrollment>
    <condition>Polycystic Ovary Syndrome</condition>
    <arm_group>
      <arm_group_label>SGLT2 inhibitors combined with metformin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Intervention with henggliflozin (5mg qd) and metformin (500mg bid) for 3 months</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo combined with metformin</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Intervention with placebo (qd) and metformin (500mg bid) for 3 months</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SGLT2 inhibitors combined with metformin</intervention_name>
      <description>Sodium-glucose cotransporters inhibitors (SGLT2i) are novel hypoglycemic drugs with unique hypoglycemic mechanisms, which are completely independent of islet β-cell function or insulin sensitivity. Previous studies have shown that SGLT2i may improve IR by inhibiting glucotoxicity, reducing body weight, reducing inflammation, improving islet β-cell function, and reducing oxidative stress.</description>
      <arm_group_label>SGLT2 inhibitors combined with metformin</arm_group_label>
      <other_name>Henggliflozin combined with metformin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo combined with metformin</intervention_name>
      <description>Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.</description>
      <arm_group_label>Placebo combined with metformin</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Female aged 18-45&#xD;
  &#xD;
            -  Meet Rotterdam criteria&#xD;
  &#xD;
            -  Insulin resistance&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Treatment with any additional medications that might impede the trial, including GLP-1&#xD;
               RAs, metformin, pioglitazone, contraceptives, or traditional Chinese medicine within&#xD;
               the past 3 months&#xD;
  &#xD;
            -  Pregnancy or lactation&#xD;
  &#xD;
            -  Mental illness&#xD;
  &#xD;
            -  Malignant tumors&#xD;
  &#xD;
            -  Chronic kidney disease or severe liver dysfunction&#xD;
  &#xD;
            -  Inflammatory bowel disease&#xD;
  &#xD;
            -  Involvement in other research programs within the past 3 months&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai 10th People's Hospital</investigator_affiliation>
      <investigator_full_name>Zhang Manna</investigator_full_name>
      <investigator_title>Director, principal investigator, clinical professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Polycystic Ovary Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metformin</mesh_term>
      <mesh_term>Sodium-Glucose Transporter 2 Inhibitors</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05966792
  org study id: SGLT2i NLRP3 PCOS
  nct id: NCT05966792
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Chronic inflammation is the core of Polycystic ovary syndrome (PCOS), and obesity and
        overweight further exacerbate the level of inflammation in the peripheral circulation and
        ovarian tissue in PCOS patients. Metformin is a classic endocrine drug for the treatment of
        PCOS, but its clinical response rate is only about 40%. Our previous published study
        (Diabetes Obes Metab, 2022) observed that the new hypoglycemic drug SGLT-2 inhibitor can
        significantly improve the clinical symptoms of patients with insulin resistance PCOS, and the
        clinical efficacy is not inferior to metformin, but its specific mechanism of action is not
        clear. Recent studies have shown that SGLT-2 significantly attenuates the activation of the
        Nod-like receptor protein 3 (NLRP3) inflammasomes and the secretion of IL-1β in patients with
        type 2 diabetes mellitus at high risk of cardiovascular disease. Based on the above research
        background, this project will combine clinical research and mechanism exploration to solve
        the following two problems:
  
          1. whether metformin plus SGLT2 inhibitor can further improve the clinical efficacy of PCOS
             patients compared to metformin plus placebo;
  
          2. mechanistic studies further clarify whether SGLT2 inhibitors improve inflammatory
             symptoms by modulating NLRP3 inflammosomes in the treatment of polycystic ovary
             syndrome;
  This clinical study is a prospective, single-center, randomized (1:1) controlled clinical
        study. The enrollment population is overweight or obese PCOS patients. After signing the
        informed consent form, patients who meet the inclusion/exclusion criteria will be randomly
        assigned to the experimental and control groups for treatment in a 1:1 ratio, for a total of
        72 patients enrolled.
  
        Subjects randomized to the trial group will receive SGLT-2 inhibitors plus metformin for 12
        weeks.
  
        Participants randomised to control will receive placebo plus metformin for 12 weeks.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: HOMA-IR
  time frame: 3 months
  description: Homeostatic model assessment insulin resistance index
  measure: Menstrual cycles
  time frame: 3 months
  description: annual number of menstrual cycles
  measure: NLRP3
  time frame: 3 months
  description: Nod-like receptor protein 3
  measure: IL-1β
  time frame: 3 months
  description: Interleukin-1 beta
  measure: IL-18
  time frame: 3 months
  description: Interleukin-18
  measure: LH
  time frame: 3 months
  description: luteinizing hormone
  measure: FSH
  time frame: 3 months
  description: follicle-stimulating hormone
  measure: PRL
  time frame: 3 months
  description: prolactin
  measure: E2
  time frame: 3 months
  description: estradiol
  measure: P
  time frame: 3 months
  description: progesterone
  measure: TT
  time frame: 3 months
  description: total testosterone
  arm group label: SGLT2 inhibitors combined with metformin
  arm group type: Experimental
  description: Intervention with henggliflozin (5mg qd) and metformin (500mg bid) for 3 months
  arm group label: Placebo combined with metformin
  arm group type: Placebo Comparator
  description: Intervention with placebo (qd) and metformin (500mg bid) for 3 months
  intervention type: Drug
  intervention name: SGLT2 inhibitors combined with metformin
  description: Sodium-glucose cotransporters inhibitors (SGLT2i) are novel hypoglycemic drugs with unique hypoglycemic mechanisms, which are completely independent of islet β-cell function or insulin sensitivity. Previous studies have shown that SGLT2i may improve IR by inhibiting glucotoxicity, reducing body weight, reducing inflammation, improving islet β-cell function, and reducing oxidative stress.
  arm group label: SGLT2 inhibitors combined with metformin
  other name: Henggliflozin combined with metformin
  intervention type: Drug
  intervention name: Placebo combined with metformin
  description: Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.
  arm group label: Placebo combined with metformin
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai 10th People's Hospital
  investigator full name: Zhang Manna
  investigator title: Director, principal investigator, clinical professor
  mesh term: Polycystic Ovary Syndrome
  mesh term: Syndrome
  mesh term: Metformin
  mesh term: Sodium-Glucose Transporter 2 Inhibitors
  sharing ipd: No