Type 2 Diabetes Mellitus With ComplicationNCT05513729
Effect of Canagliflozin on Liver Inflammation Damage in Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease
An observational study of Type 2 Diabetes Mellitus With Complication, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus With Complication
- What is being tested?
- Canagliflozin and Pioglitazone
- Type of treatment
- Pill or oral medicine
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 18 Aug 2022to 1 Mar 2024
- How long will I take part?
- 6 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease who have been treated with metformin monotherapy for at least 3 months.
Who may be able to join
- 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;
Who cannot join
- 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.;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital Xi'an Jiaotong University
Xi'an, Shannxi, 710061
About this study
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
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.
Read the 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.
- Being tested
- Canagliflozin, Pioglitazone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanagliflozinDrug
Also called Canagliflozin tablets
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.
PioglitazoneDrug
Also called Pioglitazone Hydrochloride Tablets
According to the newest guideline of Diabetes，pioglitazone will be given to 40 patients with T2DM combined with NAFLD if their HbA1c above target.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Canagliflozin | |
| 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. Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma cholesteryl ester transfer protein(CETP) concentration(ug/mL)
Measurements of liver inflammation and damage
Measured: 24 weeks after the date of enrollment
The activity of CEPT in pmol/mL/min
Measurements of liver inflammation and damage
Measured: Time Frame: 24 weeks after the date of enrollment
Secondary outcomes (2)
Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
Measurements of liver inflammation and damage
Measured: Baseline
The activity of CEPT in pmol/mL/min
Measurements of liver inflammation and damage
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2022
- Study start18 Aug 2022
- Primary completion31 Dec 2023 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes Mellitus With ComplicationStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- YAYI HE, Principal investigator, First Affiliated Hospital Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05513729
- Sponsor's protocol ID
- XJTU1AF2022LSK-319
- Status last verified
- Aug 2022
- First submitted
- 22 Aug 2022
- Last updated
- 24 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05513729
- Acronym / sponsor ID
- XJTU1AF2022LSK-319
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- 18 Aug 2022 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 24 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Canagliflozin treatment group | – | Drug: Canagliflozin40 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. |
| Pioglitazone treatment group | – | Drug: Pioglitazone40 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Type 2 Diabetes Patients With Nonalcoholic Fatty Liver Disease who have been treated with metformin monotherapy for at least 3 months.
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanagliflozinAlso: Canagliflozin tabletsAccording 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. | Drug | Canagliflozin treatment group |
| PioglitazoneAlso: Pioglitazone Hydrochloride TabletsAccording to the newest guideline of Diabetes，pioglitazone will be given to 40 patients with T2DM combined with NAFLD if their HbA1c above target. | Drug | Pioglitazone treatment group |
Primary outcome
Plasma cholesteryl ester transfer protein(CETP) concentration(ug/mL)
Time frame: 24 weeks after the date of enrollment
Measurements of liver inflammation and damage
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
2 secondary outcomes
Plasma cholesteryl ester transfer protein(CETP) concentration in ug/mL
Time frame: Baseline
The activity of CEPT in pmol/mL/min
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
YAYI HE principal investigator
First Affiliated Hospital Xi'an Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes Mellitus With Complication, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact YAYI HE (0086-15934880897, mailto:008099@xjtufh.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma cholesteryl ester transfer protein(CETP) concentration(ug/mL) (time frame: 24 weeks after the date of enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.