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Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease

Primary Purpose

Type 2 Diabetes Mellitus With Complication

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Canagliflozin
Pioglitazone
Sponsored by
First Affiliated Hospital Xi'an Jiaotong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Type 2 Diabetes Mellitus With Complication

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Meets the diagnostic criteria for type 2 diabetes(1999 WHO criteria).
  • Meets the diagnostic criteria for non-alcoholic fatty liver disease (2018 Chinese Medical Association Treatment Guidelines ), and liver ultrasound showed moderate or higher fatty liver.
  • Metformin monotherapy for 3 months, but with poor glycemic control (7.5%≤HbA1c≤10.5%))
  • Obese or overweight when screening (BMI>24kg/m2);
  • 18 years old ≤ age ≤ 70 years old;
  • Have a good follow-up compliance, with follow-up months ≥ 24 weeks;

Exclusion Criteria:

  • Non-type 2 diabetes: type 1 diabetes, gestational diabetes, or other specific types of diabetes;
  • Diabetes patients with acute and chronic complications and serious infections; Pregnant and lactating women;
  • Those who have allergies or toxic side effects or contraindications to canagliflozin, pioglitazone and other drugs;
  • Active sexually transmitted diseases such as viral hepatitis, AIDS and syphilis, and infectious diseases such as tuberculosis;
  • Have a weight change of more than 10% in the 3 months prior to screening;
  • Have used other drugs that may affect blood glucose metabolism in the past 2 months, including systemic glucocorticoids (except inhalation or topical use), growth hormone, etc.;
  • Have used any sodium-glucose cotransporter-2 (SGLT-2) inhibitor or thiazolidinediones;
  • History of more than 2 severe hypoglycemic episodes in the past 1 year;
  • History or condition of any of the following: decompensated cardiac insufficiency (NYHA class III or IV); history of unstable angina, myocardial infarction, coronary artery bypass grafting, or coronary stenting; uncontrolled or severe heart rhythm Disorders (such as long QT syndrome, etc.), and evaluated by the investigator to be unsuitable to participate in this clinical trial; currently accompanied by clinically significant urinary tract/reproductive infection, or a history of complicated urinary tract infection, or nearly 6 A history of recurrent urinary tract infections within a month;
  • Currently known to have severe osteoporosis, or a history of secondary fractures within the past 1 year;
  • Any laboratory tests meet the following criteria: fasting plasma/serum glucose ≥ 15 mmol/L; alanine aminotransferase or aspartate aminotransferase > 3 times the upper limit of normal or total bilirubin > 1.5 times normal Upper limit; hemoglobin <100 g/L; glomerular filtration rate (eGFR) < 60 mL/min/1.73m2; fasting triglycerides > 5.64 mmol/L (500 mg/dL);
  • Has received or is receiving any other experimental drug/trial device treatment within the past 3 months;
  • Other conditions deemed inappropriate by the investigator to participate in this trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Canagliflozin treatment group

    Pioglitazone treatment group

    Arm Description

    Canagliflozin 100mg were given to the patients for 24 weeks

    Pioglitazone 30mg were given to the patients and the dosage will be increased to 45mg 2 weeks later

    Outcomes

    Primary Outcome Measures

    Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
    Measurements of liver inflammation and damage
    The activity of CEPT in pmol/mL/min
    Measurements of liver inflammation and damage

    Secondary Outcome Measures

    Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
    Measurements of liver inflammation and damage
    The activity of CEPT in pmol/mL/min
    Measurements of liver inflammation and damage

    Full Information

    First Posted
    June 9, 2022
    Last Updated
    September 18, 2022
    Sponsor
    First Affiliated Hospital Xi'an Jiaotong University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05422092
    Brief Title
    Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease
    Official Title
    Therapeutic Effects of Canagliflozin on the Liver Inflammation Damage and Lipoprotein Metabolism in Patients With Type 2 Diabetes Mellitus Combined With Nonalcoholic Fatty Liver Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 20, 2022 (Anticipated)
    Primary Completion Date
    January 2023 (Anticipated)
    Study Completion Date
    December 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    First Affiliated Hospital Xi'an Jiaotong University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Type 2 diabetes mellitus (T2DM) is always accompanied with nonalcoholic fatty liver disease (NAFLD).This prospective, randomized controlled intervention study was designed to reveal the potential clinical application and underlying mechanisms of canagliflozin in the treatment of type 2 diabetes combined with nonalcoholic fatty liver disease.
    Detailed Description
    Type 2 diabetes mellitus (T2DM) is one of the most important risk factors for nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH). Thus far, there are no approved medicines to treat NAFLD/NASH and none of plasma biomarkers are sufficient to accurately and rapidly diagnose NASH in clinic. Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that not only reduces glycemia, blood pressure and albuminuria, but also lowers body weight and improves dyslipidemia. However, whether canagliflozin can be used to treat NAFLD/NASH and its impacts on lipid and lipoprotein metabolism are still rather obscure. Based on findings from the previous studies, the investigators propose the following hypothesis: canagliflozin decreases body fat mass, in particular the visceral fat depots and liver fat content, thus alleviating hepatic steatosis, hepatic macrophage content and activation. Since the investigators have demonstrated for the first time that plasma cholesteryl ester transfer protein (CETP) is predominantly derived from hepatic macrophages, and CETP plays a pivotal role in regulating lipid and lipoprotein metabolism. Moreover, plasma CETP concentration and activity can be applied as an effective biomarker for hepatic steatosis and liver inflammation and damage. Collectively, in this study, 80 patients with T2DM combined with NAFLD, who have poor glycemic control response to metformin monotherapy, will be randomly assigned to receive canagliflozin or pioglitazone (as placebo control) on top of metformin. The primary outcome will be plasma CETP concentration and activity, as measurements of liver lipid content, hepatic steatosis, liver inflammation and damage. The secondary outcome will be nuclear magnetic resonance spectroscopy- based metabolomics, including lipoprotein profile, lipid species and metabolomic, to comprehensively evaluate the therapeutic effects of canagliflozin on lipids and lipoproteins. The investigators anticipate this prospective, randomized controlled intervention study will reveal the potential clinical application and underlying mechanisms of canagliflozin in the treatment of NAFLD/NASH, and also provide a theoretical basis for predicting its effect on cardiovascular disease events, thus having important economic value and scientific significance.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 2 Diabetes Mellitus With Complication

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Canagliflozin treatment group
    Arm Type
    Experimental
    Arm Description
    Canagliflozin 100mg were given to the patients for 24 weeks
    Arm Title
    Pioglitazone treatment group
    Arm Type
    Placebo Comparator
    Arm Description
    Pioglitazone 30mg were given to the patients and the dosage will be increased to 45mg 2 weeks later
    Intervention Type
    Drug
    Intervention Name(s)
    Canagliflozin
    Other Intervention Name(s)
    Canagliflozin tablets
    Intervention Description
    40 patients with T2DM combined with NAFLD, who have poor glycemic control response to metformin monotherapy, will be randomly assigned to receive canagliflozin on top of metformin as experimental group.
    Intervention Type
    Drug
    Intervention Name(s)
    Pioglitazone
    Other Intervention Name(s)
    Pioglitazone Hydrochloride Tablets
    Intervention Description
    40 patients with T2DM combined with NAFLD, who have poor glycemic control response to metformin monotherapy, will be randomly assigned to receive pioglitazone 45mg on top of metformin as placebo comparator group.
    Primary Outcome Measure Information:
    Title
    Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
    Description
    Measurements of liver inflammation and damage
    Time Frame
    24 weeks after the date of enrollment
    Title
    The activity of CEPT in pmol/mL/min
    Description
    Measurements of liver inflammation and damage
    Time Frame
    24 weeks after the date of enrollment
    Secondary Outcome Measure Information:
    Title
    Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
    Description
    Measurements of liver inflammation and damage
    Time Frame
    Baseline
    Title
    The activity of CEPT in pmol/mL/min
    Description
    Measurements of liver inflammation and damage
    Time Frame
    Baseline

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Meets the diagnostic criteria for type 2 diabetes(1999 WHO criteria). Meets the diagnostic criteria for non-alcoholic fatty liver disease (2018 Chinese Medical Association Treatment Guidelines ), and liver ultrasound showed moderate or higher fatty liver. Metformin monotherapy for 3 months, but with poor glycemic control (7.5%≤HbA1c≤10.5%)) Obese or overweight when screening (BMI>24kg/m2); 18 years old ≤ age ≤ 70 years old; Have a good follow-up compliance, with follow-up months ≥ 24 weeks; Exclusion Criteria: Non-type 2 diabetes: type 1 diabetes, gestational diabetes, or other specific types of diabetes; Diabetes patients with acute and chronic complications and serious infections; Pregnant and lactating women; Those who have allergies or toxic side effects or contraindications to canagliflozin, pioglitazone and other drugs; Active sexually transmitted diseases such as viral hepatitis, AIDS and syphilis, and infectious diseases such as tuberculosis; Have a weight change of more than 10% in the 3 months prior to screening; Have used other drugs that may affect blood glucose metabolism in the past 2 months, including systemic glucocorticoids (except inhalation or topical use), growth hormone, etc.; Have used any sodium-glucose cotransporter-2 (SGLT-2) inhibitor or thiazolidinediones; History of more than 2 severe hypoglycemic episodes in the past 1 year; History or condition of any of the following: decompensated cardiac insufficiency (NYHA class III or IV); history of unstable angina, myocardial infarction, coronary artery bypass grafting, or coronary stenting; uncontrolled or severe heart rhythm Disorders (such as long QT syndrome, etc.), and evaluated by the investigator to be unsuitable to participate in this clinical trial; currently accompanied by clinically significant urinary tract/reproductive infection, or a history of complicated urinary tract infection, or nearly 6 A history of recurrent urinary tract infections within a month; Currently known to have severe osteoporosis, or a history of secondary fractures within the past 1 year; Any laboratory tests meet the following criteria: fasting plasma/serum glucose ≥ 15 mmol/L; alanine aminotransferase or aspartate aminotransferase > 3 times the upper limit of normal or total bilirubin > 1.5 times normal Upper limit; hemoglobin <100 g/L; glomerular filtration rate (eGFR) < 60 mL/min/1.73m2; fasting triglycerides > 5.64 mmol/L (500 mg/dL); Has received or is receiving any other experimental drug/trial device treatment within the past 3 months; Other conditions deemed inappropriate by the investigator to participate in this trial.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    YAYI HE
    Phone
    0086-15934880897
    Email
    008099@xjtufh.edu.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    YAYI He
    Organizational Affiliation
    First Affiliated Hospital Xi'an Jiaotong University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease

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