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Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis

Primary Purpose

Diabetic Nephropathies

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Henagliflozin
Placebo
Sponsored by
Qianfoshan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetic Nephropathies focused on measuring Henagliflozin, Diabetic Nephropathy, enteric microorganisms

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1.18-65 years old, regardless of gender; 2. It was confirmed as DKD by renal biopsy. 3. It needs to be treated with DKD standard scheme, but it can be adjusted according to needs. 4.eGFR>30ml/min/1.73m2 5.200mg/g<UACR<5000mg/g 6. Stabilize the maximum tolerated dose ACEi/ARB ≥4 weeks. 7. Volunteer to participate in the study, understand the significance of this experiment and the indicators to be measured, and sign the informed consent form. Exclusion Criteria: 1. Severe infection: there are clinical manifestations such as fever, cough and expectoration, sore throat, abdominal pain, diarrhea, carbuncle and furuncle, and the white blood cell count in blood is beyond the normal range (10× 109/L); 2. Severe hypoproteinemia (albumin < 20g/L) 3 malnutrition or BMI<18.5 kg/m2. 4. Hemoglobin < 60g/L; 5. No full capacity; 6. Severe hypotension (< 90/60mmhg); 7. Severe hypertension (> 180/110mmHg). Have used SGLT2i of any kind, dosage and dosage form within 8.6 months or are intolerant of such drugs. 9.1 type diabetes mellitus 10. Patients who have had ketoacidosis, diabetic coma or multiple hypoglycemia episodes in the past. 11. Polycystic kidney disease, lupus nephritis, ANCA- related vasculitis. 12. Immunosuppressant treatment for 6 months or less before enrollment. 13. Severe heart failure (NYHA grade ≧II-III) 14. Other serious heart diseases, such as recent myocardial infarction, persistent atrial fibrillation and valvular heart disease. 15 patients with severe liver dysfunction (ALT or AST>3 times the normal upper limit, or total bilirubin > 2 times the normal upper limit) 16. Chronic cystitis, or urinary tract infection ≥3 times within 1 year. 17 patients with obvious bleeding tendency or blood system diseases, or patients with bone marrow suppression. 18. Malignant tumor 19. Pregnant women, lactating patients or patients who plan to become pregnant. 20. There are acute or severe systemic infections. 21. The subject is participating in clinical trials of other drugs or medical devices. 22. Any known drug or alcohol dependence, difficulty in understanding the trial protocol, and inability or unwillingness to follow up according to the trial protocol. 23. Moderate and severe cognitive impairment and no long-term fixed guardian. 24. Chronic diarrhea and indigestion 25. Patients that the researcher thinks are not suitable to participate in this trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Henagliflozin

    Placebo

    Arm 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.

    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.

    Outcomes

    Primary Outcome Measures

    Detection of intestinal flora difference between intervention group and control group with diabetic nephropathy by bacterial 16srDNA sequencing
    16srDNA sequencing was used to detect the difference of relative abundance of different kinds of intestinal flora between the two groups.

    Secondary Outcome Measures

    Statistical analysis of the degree of proteinuria relief in intervention group and control group.
    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.

    Full Information

    First Posted
    July 29, 2023
    Last Updated
    September 3, 2023
    Sponsor
    Qianfoshan Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06031389
    Brief Title
    Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis
    Official Title
    Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2024 (Anticipated)
    Primary Completion Date
    December 31, 2024 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Qianfoshan Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diabetic Nephropathies
    Keywords
    Henagliflozin, Diabetic Nephropathy, enteric microorganisms

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    120 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Henagliflozin
    Arm Type
    Experimental
    Arm 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 Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm 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(s)
    Henagliflozin
    Intervention 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention 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.
    Primary Outcome Measure Information:
    Title
    Detection of intestinal flora difference between intervention group and control group with diabetic nephropathy by bacterial 16srDNA sequencing
    Description
    16srDNA sequencing was used to detect the difference of relative abundance of different kinds of intestinal flora between the two groups.
    Time Frame
    baseline、1 month、3 month、6 month and 12 month
    Secondary Outcome Measure Information:
    Title
    Statistical analysis of the degree of proteinuria relief in intervention group and control group.
    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.
    Time Frame
    baseline、1 month、3 month、6 month and 12 month

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1.18-65 years old, regardless of gender; 2. It was confirmed as DKD by renal biopsy. 3. It needs to be treated with DKD standard scheme, but it can be adjusted according to needs. 4.eGFR>30ml/min/1.73m2 5.200mg/g<UACR<5000mg/g 6. Stabilize the maximum tolerated dose ACEi/ARB ≥4 weeks. 7. Volunteer to participate in the study, understand the significance of this experiment and the indicators to be measured, and sign the informed consent form. Exclusion Criteria: 1. Severe infection: there are clinical manifestations such as fever, cough and expectoration, sore throat, abdominal pain, diarrhea, carbuncle and furuncle, and the white blood cell count in blood is beyond the normal range (10× 109/L); 2. Severe hypoproteinemia (albumin < 20g/L) 3 malnutrition or BMI<18.5 kg/m2. 4. Hemoglobin < 60g/L; 5. No full capacity; 6. Severe hypotension (< 90/60mmhg); 7. Severe hypertension (> 180/110mmHg). Have used SGLT2i of any kind, dosage and dosage form within 8.6 months or are intolerant of such drugs. 9.1 type diabetes mellitus 10. Patients who have had ketoacidosis, diabetic coma or multiple hypoglycemia episodes in the past. 11. Polycystic kidney disease, lupus nephritis, ANCA- related vasculitis. 12. Immunosuppressant treatment for 6 months or less before enrollment. 13. Severe heart failure (NYHA grade ≧II-III) 14. Other serious heart diseases, such as recent myocardial infarction, persistent atrial fibrillation and valvular heart disease. 15 patients with severe liver dysfunction (ALT or AST>3 times the normal upper limit, or total bilirubin > 2 times the normal upper limit) 16. Chronic cystitis, or urinary tract infection ≥3 times within 1 year. 17 patients with obvious bleeding tendency or blood system diseases, or patients with bone marrow suppression. 18. Malignant tumor 19. Pregnant women, lactating patients or patients who plan to become pregnant. 20. There are acute or severe systemic infections. 21. The subject is participating in clinical trials of other drugs or medical devices. 22. Any known drug or alcohol dependence, difficulty in understanding the trial protocol, and inability or unwillingness to follow up according to the trial protocol. 23. Moderate and severe cognitive impairment and no long-term fixed guardian. 24. Chronic diarrhea and indigestion 25. Patients that the researcher thinks are not suitable to participate in this trial.

    12. IPD Sharing Statement

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    Henagliflozin Delays the Progress of Diabetic Nephropathy Via Regulates Gut-Renal Axis

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