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
About this trial
This is an interventional diagnostic trial for Type 2 Diabetes Mellitus With Complication
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.
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
NCT ID
NCT05422092
First Posted
June 9, 2022
Last Updated
September 18, 2022
Sponsor
First Affiliated Hospital Xi'an Jiaotong University
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
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Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease
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