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/NCT06031389</url>
    </required_header>
    <id_info>
      <org_study_id>HENA-DKD</org_study_id>
      <nct_id>NCT06031389</nct_id>
    </id_info>
    <brief_title>Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis</brief_title>
    <official_title>Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qianfoshan Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qianfoshan Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Diabetic kidney disease (DKD) is a serious complication of diabetes, and it is also the&#xD;
        leading cause of end-stage renal disease (ESRD) in the world. The aggravation of progressive&#xD;
        proteinuria and the decrease of glomerular filtration rate are the important reasons for the&#xD;
        development of DKD into ESRD. It is an important task in the medical field to delay the&#xD;
        development of DKD into ESRD. In recent years, gut microbiota disorder has been considered as&#xD;
        an important influencing factor of DKD, and the concept of gut-renal axis has attracted more&#xD;
        and more attention. The disorder of gut microbiota in DKD patients is mainly manifested by&#xD;
        the decrease in the abundance of probiotics such as Lactobacillus, Bifidobacterium and&#xD;
        Akkermansia, which produce short-chain fatty acids (SCFA), and the increase in the abundance&#xD;
        of uremic toxin-producing bacteria such as Ruminococcus, Alistipes and Subdoligranulum.&#xD;
        Improving gut microbiota disorder and increasing the concentration of beneficial metabolites&#xD;
        such as SCFA in serum have positive effects on improving DKD. In recent years, with the&#xD;
        application of sodium-glucose cotransporter 2 inhibitors (SGLT-2i), diabetes has been&#xD;
        effectively treated. SGLT-2i can reduce blood glucose concentration by inhibiting renal&#xD;
        tubular glucose reabsorption, and at the same time, it can play a renal protection role&#xD;
        independent of blood glucose reduction by correcting the unbalanced tubuloglomerular feedback&#xD;
        during diabetes and improving inflammation. However, the mechanism of its renal protection&#xD;
        seems to be more than that. Studies have shown that SGLT-2i can reduce proteinuria in DKD&#xD;
        mice by regulating the disordered gut microbiota during DKD, but not all SGLT-2i preparations&#xD;
        have the effect of protecting target organs by regulating gut microbiota. Wang found that&#xD;
        canagliflozin can regulate the gut microbiota of diabetes mice and improve cardiovascular&#xD;
        complications; Lee reported that dapagliflozin could reduce the ratio of&#xD;
        Firmicutes/Bacteroides in DKD mice and increase the abundance of Akkermansia. Yang found that&#xD;
        dapagliflozin increased the abundance of Proteobacteria in diabetes rats, but it did not seem&#xD;
        to affect the ratio of Firmicutes/Bacteroides. Van Bommel reported that dapagliflozin would&#xD;
        not affect the gut microbiot of diabetes patients. Whether henagliflozin can improve DKD by&#xD;
        regulating the gut-renal axis is worthy of further study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>N/A</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>Basic Science</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Detection of intestinal flora difference between intervention group and control group with diabetic nephropathy by bacterial 16srDNA sequencing</measure>
      <time_frame>baseline、1 month、3 month、6 month and 12 month</time_frame>
      <description>16srDNA sequencing was used to detect the difference of relative abundance of different kinds of intestinal flora between the two groups.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Statistical analysis of the degree of proteinuria relief in intervention group and control group.</measure>
      <time_frame>baseline、1 month、3 month、6 month and 12 month</time_frame>
      <description>T-test or Wilcoxon rank-sum test were used to compare the difference of urinary microalbumin creatinine ratio in two groups of diabetic nephropathy patients in regular urine biochemical tests.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Diabetic Nephropathies</condition>
    <arm_group>
      <arm_group_label>Henagliflozin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>On the basis of basic treatment, the patients in the Hengglinide（tabuletta） intervention group were given Hengglinide once a day, 10mg or 5mg each time in the morning, and continued to intervene for 12 months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The blank control group was treated with placebo (starch tablets) once a day, 10mg or 5mg each time, taken in the morning for 12 months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Henagliflozin</intervention_name>
      <description>On the basis of hypoglycemic therapy, the patients in the intervention group were given the drug treatment of hengglinide, once a day, 10mg or 5mg each time, taken in the morning, for 12 months.</description>
      <arm_group_label>Henagliflozin</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>On the basis of basic treatment, patients in the blank control group were given starch tablets once a day, 10mg or 5mg each time, taken in the morning for 12 months.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1.18-65 years old, regardless of gender; 2. It was confirmed as DKD by renal biopsy. 3. It&#xD;
          needs to be treated with DKD standard scheme, but it can be adjusted according to needs.&#xD;
  &#xD;
          4.eGFR&gt;30ml/min/1.73m2 5.200mg/g&lt;UACR&lt;5000mg/g 6. Stabilize the maximum tolerated dose&#xD;
          ACEi/ARB ≥4 weeks. 7. Volunteer to participate in the study, understand the significance of&#xD;
          this experiment and the indicators to be measured, and sign the informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          1. Severe infection: there are clinical manifestations such as fever, cough and&#xD;
          expectoration, sore throat, abdominal pain, diarrhea, carbuncle and furuncle, and the white&#xD;
          blood cell count in blood is beyond the normal range (10× 109/L); 2. Severe hypoproteinemia&#xD;
          (albumin &lt; 20g/L) 3 malnutrition or BMI&lt;18.5 kg/m2. 4. Hemoglobin &lt; 60g/L; 5. No full&#xD;
          capacity; 6. Severe hypotension (&lt; 90/60mmhg); 7. Severe hypertension (&gt; 180/110mmHg). Have&#xD;
          used SGLT2i of any kind, dosage and dosage form within 8.6 months or are intolerant of such&#xD;
          drugs.&#xD;
  &#xD;
          9.1 type diabetes mellitus 10. Patients who have had ketoacidosis, diabetic coma or&#xD;
          multiple hypoglycemia episodes in the past.&#xD;
  &#xD;
          11. Polycystic kidney disease, lupus nephritis, ANCA- related vasculitis. 12.&#xD;
          Immunosuppressant treatment for 6 months or less before enrollment. 13. Severe heart&#xD;
          failure (NYHA grade ≧II-III) 14. Other serious heart diseases, such as recent myocardial&#xD;
          infarction, persistent atrial fibrillation and valvular heart disease.&#xD;
  &#xD;
          15 patients with severe liver dysfunction (ALT or AST&gt;3 times the normal upper limit, or&#xD;
          total bilirubin &gt; 2 times the normal upper limit) 16. Chronic cystitis, or urinary tract&#xD;
          infection ≥3 times within 1 year. 17 patients with obvious bleeding tendency or blood&#xD;
          system diseases, or patients with bone marrow suppression.&#xD;
  &#xD;
          18. Malignant tumor 19. Pregnant women, lactating patients or patients who plan to become&#xD;
          pregnant. 20. There are acute or severe systemic infections. 21. The subject is&#xD;
          participating in clinical trials of other drugs or medical devices.&#xD;
  &#xD;
          22. Any known drug or alcohol dependence, difficulty in understanding the trial protocol,&#xD;
          and inability or unwillingness to follow up according to the trial protocol.&#xD;
  &#xD;
          23. Moderate and severe cognitive impairment and no long-term fixed guardian. 24. Chronic&#xD;
          diarrhea and indigestion 25. Patients that the researcher thinks are not suitable to&#xD;
          participate in this trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 29, 2023</study_first_submitted>
    <study_first_submitted_qc>September 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 3, 2023</last_update_submitted>
    <last_update_submitted_qc>September 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Qianfoshan Hospital</investigator_affiliation>
      <investigator_full_name>Zunsong Wang</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <keyword>Henagliflozin</keyword>
    <keyword>Diabetic Nephropathy</keyword>
    <keyword>enteric microorganisms</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Kidney Diseases</mesh_term>
      <mesh_term>Diabetic Nephropathies</mesh_term>
    </condition_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/NCT06031389
  org study id: HENA-DKD
  nct id: NCT06031389
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Diabetic kidney disease (DKD) is a serious complication of diabetes, and it is also the
        leading cause of end-stage renal disease (ESRD) in the world. The aggravation of progressive
        proteinuria and the decrease of glomerular filtration rate are the important reasons for the
        development of DKD into ESRD. It is an important task in the medical field to delay the
        development of DKD into ESRD. In recent years, gut microbiota disorder has been considered as
        an important influencing factor of DKD, and the concept of gut-renal axis has attracted more
        and more attention. The disorder of gut microbiota in DKD patients is mainly manifested by
        the decrease in the abundance of probiotics such as Lactobacillus, Bifidobacterium and
        Akkermansia, which produce short-chain fatty acids (SCFA), and the increase in the abundance
        of uremic toxin-producing bacteria such as Ruminococcus, Alistipes and Subdoligranulum.
        Improving gut microbiota disorder and increasing the concentration of beneficial metabolites
        such as SCFA in serum have positive effects on improving DKD. In recent years, with the
        application of sodium-glucose cotransporter 2 inhibitors (SGLT-2i), diabetes has been
        effectively treated. SGLT-2i can reduce blood glucose concentration by inhibiting renal
        tubular glucose reabsorption, and at the same time, it can play a renal protection role
        independent of blood glucose reduction by correcting the unbalanced tubuloglomerular feedback
        during diabetes and improving inflammation. However, the mechanism of its renal protection
        seems to be more than that. Studies have shown that SGLT-2i can reduce proteinuria in DKD
        mice by regulating the disordered gut microbiota during DKD, but not all SGLT-2i preparations
        have the effect of protecting target organs by regulating gut microbiota. Wang found that
        canagliflozin can regulate the gut microbiota of diabetes mice and improve cardiovascular
        complications; Lee reported that dapagliflozin could reduce the ratio of
        Firmicutes/Bacteroides in DKD mice and increase the abundance of Akkermansia. Yang found that
        dapagliflozin increased the abundance of Proteobacteria in diabetes rats, but it did not seem
        to affect the ratio of Firmicutes/Bacteroides. Van Bommel reported that dapagliflozin would
        not affect the gut microbiot of diabetes patients. Whether henagliflozin can improve DKD by
        regulating the gut-renal axis is worthy of further study.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Single (Participant)
  measure: Detection of intestinal flora difference between intervention group and control group with diabetic nephropathy by bacterial 16srDNA sequencing
  time frame: baseline、1 month、3 month、6 month and 12 month
  description: 16srDNA sequencing was used to detect the difference of relative abundance of different kinds of intestinal flora between the two groups.
  measure: Statistical analysis of the degree of proteinuria relief in intervention group and control group.
  time frame: baseline、1 month、3 month、6 month and 12 month
  description: T-test or Wilcoxon rank-sum test were used to compare the difference of urinary microalbumin creatinine ratio in two groups of diabetic nephropathy patients in regular urine biochemical tests.
  arm group label: Henagliflozin
  arm group type: Experimental
  description: On the basis of basic treatment, the patients in the Hengglinide（tabuletta） intervention group were given Hengglinide once a day, 10mg or 5mg each time in the morning, and continued to intervene for 12 months.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: The blank control group was treated with placebo (starch tablets) once a day, 10mg or 5mg each time, taken in the morning for 12 months.
  intervention type: Drug
  intervention name: Henagliflozin
  description: On the basis of hypoglycemic therapy, the patients in the intervention group were given the drug treatment of hengglinide, once a day, 10mg or 5mg each time, taken in the morning, for 12 months.
  arm group label: Henagliflozin
  intervention type: Drug
  intervention name: Placebo
  description: On the basis of basic treatment, patients in the blank control group were given starch tablets once a day, 10mg or 5mg each time, taken in the morning for 12 months.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Qianfoshan Hospital
  investigator full name: Zunsong Wang
  investigator title: Director
  mesh term: Kidney Diseases
  mesh term: Diabetic Nephropathies