- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05513729
Effect of Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease
August 22, 2022 updated by: First Affiliated Hospital Xi'an Jiaotong University
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
Type 2 diabetes mellitus (T2DM) is always accompanied with nonalcoholic fatty liver disease (NAFLD).This prospective 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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 dyslipidaemia.
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 our previous studies, we 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 we 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 been given metformin monotherapy for at least 3 months, will be assigned to receive canagliflozin or pioglitazone (as placebo control) on top of metformin according to the guideline of Type 2 diabets.
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.
We anticipate this prospective 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.
Study Type
Observational
Enrollment (Anticipated)
80
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: YAYI HE
- Phone Number: 0086-15934880897
- Email: 008099@xjtufh.edu.cn
Study Contact Backup
- Name: YAYI HE
- Phone Number: 0086-15934880897
- Email: mailto:008099@xjtufh.edu.cn
Study Locations
-
-
Shannxi
-
Xi'an, Shannxi, China, 710061
- Recruiting
- First Affiliated Hospital Xi'an Jiaotong University
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease who have been treated with metformin monotherapy for at least 3 months.
Description
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
- 8 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 in the 3 months prior to screening;
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Canagliflozin treatment group
40 patients with T2DM combined with NAFLD will be assigned to receive canagliflozin on top of metformin monotherapy according to clinical guideline of type 2 diabetes as experimental group.
|
According to the guideline of type 2 diabetes,canagliflozin will be given to 40 patients with type 2 diabetes combined with NAFLD as first-line choice if accompanied with indicators of high risk or established atherosclerotic cardiovascular disease, chronic kidney disease or heart failure, independently of HbA1c level.
It can be also given to T2DM combined with NAFLD if their HbA1c above target.
Other Names:
|
Pioglitazone treatment group
40 patients with T2DM combined with NAFLD will be assigned to receive pioglitazone on top of metformin monotherapy according to clinical guideline of type 2 diabetes as experimental group.
as placebo comparator group.
|
According to the newest guideline of Diabetes,pioglitazone will be given to 40 patients with T2DM combined with NAFLD if their HbA1c above target.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma cholesteryl ester transfer protein(CETP) concentration(ug/mL)
Time Frame: 24 weeks after the date of enrollment
|
Measurements of liver inflammation and damage
|
24 weeks after the date of enrollment
|
The activity of CEPT in pmol/mL/min
Time Frame: Time Frame: 24 weeks after the date of enrollment
|
Measurements of liver inflammation and damage
|
Time Frame: 24 weeks after the date of enrollment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
Time Frame: Baseline
|
Measurements of liver inflammation and damage
|
Baseline
|
The activity of CEPT in pmol/mL/min
Time Frame: Baseline
|
Measurements of liver inflammation and damage
|
Baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: YAYI HE, First Affiliated Hospital Xi'an Jiaotong University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 18, 2022
Primary Completion (Anticipated)
December 31, 2023
Study Completion (Anticipated)
March 1, 2024
Study Registration Dates
First Submitted
August 22, 2022
First Submitted That Met QC Criteria
August 22, 2022
First Posted (Actual)
August 24, 2022
Study Record Updates
Last Update Posted (Actual)
August 24, 2022
Last Update Submitted That Met QC Criteria
August 22, 2022
Last Verified
August 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Liver Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Inflammation
- Hepatitis
- Fatty Liver
- Non-alcoholic Fatty Liver Disease
- Diabetes Complications
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Sodium-Glucose Transporter 2 Inhibitors
- Pioglitazone
- Canagliflozin
Other Study ID Numbers
- XJTU1AF2022LSK-319
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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