Type 2 DiabetesPhase 4NCT06218342
Henagliflozin in Relieving Type 2 Diabetes With Non-alcoholic Fatty Liver Disease
A Phase 4 study testing Henagliflozin and Background medication in people with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, run by Sir Run Run Shaw Hospital.
Trial summary
This study is a randomized, non-blinded clinical trial specifically designed to assess the initial feasibility and efficacy of SGLT2 inhibitors in treating NAFLD among adults diagnosed with type 2 diabetes. Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Henagliflozin and Background medication
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- No sites listed yet
- Study dates
- 15 Feb 2024to 31 Dec 2025
- Phase
- Phase 4
- 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 20 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 20 and 70 years old.
- Diagnosed with type 2 diabetes according to World Health Organization (WHO) diagnostic criteria, with evidence of fatty liver on ultrasound, and FIB-4 index >1.3.
- Willing to participate in this study and sign an informed consent form. In case the subject lacks the ability to read the informed consent form (e.g., illiterate subjects), the informed process must be witnessed by a designated person who will sign the informed consent form.
- Have not used oral antidiabetic medications or have used one to three oral antidiabetic medications (limited to metformin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, alpha-glucosidase inhibitors, or sulfonylureas) with an HbA1c between 7% and 10%, and fasting venous blood glucose ≤13.3 mmol/L.
- Have not used thiazolidinediones (TZDs), sodium-glucose co-transporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), or other antidiabetic drugs that may affect liver fat content in the last 90 days.
- Weight change of less than 5% in the last 3 months.
- If of childbearing age, must use reliable contraceptive measures.
Who cannot join
- Daily alcohol intake of >30 g in the past 10 years or daily alcohol intake of >10 g in the last year.
- History of liver diseases such as hepatitis B, chronic hepatitis C, primary biliary cholangitis (PBC), biliary obstruction disorders, drug-induced liver damage, hemochromatosis, liver cirrhosis, autoimmune hepatitis.
- Patients with decompensated liver cirrhosis, concurrent liver cancer, HIV-positive status, or substance abuse.
- Type 1 diabetes.
- Participation in other clinical trials of diabetes treatment drugs in the 3 months prior to the start of this study.
- Occurrence of diabetic ketoacidosis, diabetic lactic acidosis, or hyperosmolar non-ketotic coma in the past 6 months.
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- Occurrence of unexplained severe hypoglycemic events in the past 6 months (requiring assistance for recovery) or recurrent hypoglycemia: such as experiencing two or more low blood sugar events (blood glucose ≤3.9 mmol/L) in the month before screening.
- Severe heart disease patients, such as New York Heart Association (NYHA) class IV, unstable angina, or history of myocardial infarction.
- Abnormal liver function, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper normal limit, or total bilirubin (TBIL) greater than 2 times the upper normal limit.
- Chronic kidney damage, with a creatinine level (Cr) >200 µmol/L or an estimated glomerular filtration rate (eGFR) <30 mL·min-1.
- Use of corticosteroid medications (excluding short-term topical or inhaled use).
- Patients with malignant tumors, active tuberculosis, or acute/chronic infections.
- Vulnerable populations, including pregnant women, individuals with mental illness, critically ill patients, individuals with cognitive impairments, etc.
- History of recurrent urinary tract infections or genital infections, or allergies to the investigational drug or its components.
- Patients assessed by the clinical doctor as having low blood volume.
- Patients deemed unsuitable for participation in this clinical study by the investigator, for reasons not covered above.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Study of Henagliflozin in Relieving Progression of Type 2 Diabetes With Non-alcoholic Fatty Liver Disease
This study is a randomized, non-blinded clinical trial specifically designed to assess the initial feasibility and efficacy of SGLT2 inhibitors in treating NAFLD among adults diagnosed with type 2 diabetes.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that encompasses a spectrum of progressive pathological changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Epidemiological data demonstrate a close association between type 2 diabetes and NAFLD. Approximately 49% to 62% of individuals with type 2 diabetes have concurrent NAFLD, and those with NAFLD have a risk of developing diabetes more than twice that of the general population. NAFLD not only increases the risk of developing type 2 diabetes but also accelerates the progression of diabetes-related target organ damage, leading to adverse metabolic and cardiovascular risks. Currently, there is a global lack of comprehensive public health strategies for addressing NAFLD, and clinically, there are still no approved drugs specifically for treating NAFLD.
NAFLD is diagnosed through abnormal liver function test results and imaging examinations. The NAFLD Fibrosis Score (NFS) and Fibrosis-4 (FIB-4) Index can be used for clinical screening of NASH in individuals with type 2 diabetes. Ultrasound attenuation parameters (UAP) and liver stiffness measurements (LSM) based on transient elastography (TE) can accurately differentiate between liver steatosis and the degree of liver fibrosis. This technique, known for its non-invasive, safe, and reproducible nature, has found widespread application in diagnosing the extent of liver fat and fibrosis in patients with chronic liver diseases.
The primary approach to treating NAFLD involves modifying poor lifestyle habits, however, lifestyle changes are often difficult to sustain in the long term. Currently, neither the U.S. FDA nor the European Medicines Agency has approved any medications specifically for NAFLD treatment. Given the central role of insulin resistance in the development of NAFLD, hypoglycemic medications have become a new focus in the prevention and treatment of NAFLD. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, by inhibiting SGLT-2 activity, reduce the reabsorption of glucose in the proximal renal tubules, causing excess glucose to be excreted in the urine, thereby lowering blood sugar. Reports suggest that SGLT-2 inhibitors also have several other beneficial effects, including reducing the risk of cardiovascular and kidney diseases, improving blood pressure control, aiding weight reduction, and lowering liver fat content. Previous studies have shown that SGLT-2 inhibitors can improve alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and the FIB-4 Index in patients with type 2 diabetes complicated by NAFLD, potentially exhibiting anti-fibrotic effects on the liver. Henagliflozin, the SGLT-2 inhibitor used in this study, is a compound independently developed with intellectual property by Jiangsu Hengrui Medicine Co., Ltd. Henagliflozin has demonstrated efficacy and safety in monotherapy for inadequately controlled type 2 diabetes patients with poor diet and exercise control or in combination with metformin for inadequately controlled type 2 diabetes patients.
This study aims to observe the clinical efficacy of henagliflozin treatment for type 2 diabetes complicated by NAFLD in individuals, evaluating its potential to improve liver fat changes and fibrosis indicators in NAFLD, promoting NASH regression, and alleviating the progression of liver fibrosis, building upon lifestyle changes and basic treatments. The secondary objectives include investigating the effects of henagliflozin on liver fat content, visceral fat area, liver enzymes, and blood sugar improvement.
- Conditions
- Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease
- Being tested
- Henagliflozin, Background medication
- Medical subject headings
- Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HenagliflozinDrug
Besides lifestyle intervention and background medication, participants will be prescribed Henagliflozin at standard clinical doses.
Background medicationOther
Participants will only receive lifestyle intervention and background medication.
| Study group | Role | What they receive |
|---|---|---|
| Henagliflozin | Experimental | Participants in this group will receive a combination of lifestyle intervention, background medication, and Henagliflozin. The choice of hypoglycemic drugs within the background medication is restricted to either one, two, or three among metformin, DPP-4 inhibitors, alpha-glucosidase inhibitors, or secretagogues. Receives: Drug: Henagliflozin |
| Control | Other | Participants in this group will receive lifestyle intervention and background medication. The choice of hypoglycemic drugs within the background medication is restricted to either one, two, or three among metformin, DPP-4 inhibitors, alpha-glucosidase inhibitors, or secretagogues. Receives: Other: Background medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ultrasound attenuation parameter (UAP)
Changes in ultrasound attenuation parameter (UAP) from baseline. Higher UAP correlates with increased severity of steatosis.
Measured: 24 weeks
Liver stiffness measurement (LSM)
Changes in liver stiffness measurement (LSM) from baseline. Higher LSM values correlate with advancement in the stage of liver fibrosis.
Measured: 24 weeks
Secondary outcomes (8)
Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS)
Changes in Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) from baseline. Higher NFS score suggests advanced liver fibrosis.
Measured: 24 weeks
Fibrosis Index Based on 4 Factors (FIB-4 Index)
Changes in FIB-4 Index from baseline. Higher FIB-4 Index correlates with increased severity of hepatic fibrosis.
Measured: 24 weeks
Liver fat content
Changes in liver fat content from baseline
Measured: 24 weeks
Liver enzymes
Changes in liver enzymes from baseline, the enzymes include ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), and GGT (gamma-glutamyl transferase).
Measured: 24 weeks
Cholestatic proteins (Chitinase 3-like protein 1, CHI3L1)
Changes in CHI3L1 from baseline. Higher CHI3L1 level suggests advanced liver fibrosis.
Measured: 24 weeks
Intrabdominal fat
Changes in visceral fat area from baseline
Measured: 24 weeks
Glucose level
Changes in HbA1c from baseline
Measured: 24 weeks
Body weight
Changes in body weight from baseline
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start15 Feb 2024 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Sir Run Run Shaw HospitalThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sir Run Run Shaw Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jiaqiang Zhou, Principal investigator, Sir Run Run Shaw Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06218342
- Sponsor's protocol ID
- 2023412
- Status last verified
- Jan 2024
- First submitted
- 21 Nov 2023
- Last updated
- 23 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of Henagliflozin in Relieving Progression of Type 2 Diabetes With Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT06218342
- Acronym / sponsor ID
- 2023412
- Conditions
- Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Sir Run Run Shaw HospitalUniversity, hospital or other
- Study start
- 15 Feb 2024 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 23 Jan 2024 (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.
This study is a randomized, non-blinded clinical trial specifically designed to assess the initial feasibility and efficacy of SGLT2 inhibitors in treating NAFLD among adults diagnosed with type 2 diabetes.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that encompasses a spectrum of progressive pathological changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Epidemiological data demonstrate a close association between type 2 diabetes and NAFLD. Approximately 49% to 62% of individuals with type 2 diabetes have concurrent NAFLD, and those with NAFLD have a risk of developing diabetes more than twice that of the general population. NAFLD not only increases the risk of developing type 2 diabetes but also accelerates the progression of diabetes-related target organ damage, leading to adverse metabolic and cardiovascular risks. Currently, there is a global lack of comprehensive public health strategies for addressing NAFLD, and clinically, there are still no approved drugs specifically for treating NAFLD.
NAFLD is diagnosed through abnormal liver function test results and imaging examinations. The NAFLD Fibrosis Score (NFS) and Fibrosis-4 (FIB-4) Index can be used for clinical screening of NASH in individuals with type 2 diabetes. Ultrasound attenuation parameters (UAP) and liver stiffness measurements (LSM) based on transient elastography (TE) can accurately differentiate between liver steatosis and the degree of liver fibrosis. This technique, known for its non-invasive, safe, and reproducible nature, has found widespread application in diagnosing the extent of liver fat and fibrosis in patients with chronic liver diseases.
The primary approach to treating NAFLD involves modifying poor lifestyle habits, however, lifestyle changes are often difficult to sustain in the long term. Currently, neither the U.S. FDA nor the European Medicines Agency has approved any medications specifically for NAFLD treatment. Given the central role of insulin resistance in the development of NAFLD, hypoglycemic medications have become a new focus in the prevention and treatment of NAFLD. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, by inhibiting SGLT-2 activity, reduce the reabsorption of glucose in the proximal renal tubules, causing excess glucose to be excreted in the urine, thereby lowering blood sugar. Reports suggest that SGLT-2 inhibitors also have several other beneficial effects, including reducing the risk of cardiovascular and kidney diseases, improving blood pressure control, aiding weight reduction, and lowering liver fat content. Previous studies have shown that SGLT-2 inhibitors can improve alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and the FIB-4 Index in patients with type 2 diabetes complicated by NAFLD, potentially exhibiting anti-fibrotic effects on the liver. Henagliflozin, the SGLT-2 inhibitor used in this study, is a compound independently developed with intellectual property by Jiangsu Hengrui Medicine Co., Ltd. Henagliflozin has demonstrated efficacy and safety in monotherapy for inadequately controlled type 2 diabetes patients with poor diet and exercise control or in combination with metformin for inadequately controlled type 2 diabetes patients.
This study aims to observe the clinical efficacy of henagliflozin treatment for type 2 diabetes complicated by NAFLD in individuals, evaluating its potential to improve liver fat changes and fibrosis indicators in NAFLD, promoting NASH regression, and alleviating the progression of liver fibrosis, building upon lifestyle changes and basic treatments. The secondary objectives include investigating the effects of henagliflozin on liver fat content, visceral fat area, liver enzymes, and blood sugar improvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Henagliflozin | Experimental | Drug: HenagliflozinParticipants in this group will receive a combination of lifestyle intervention, background medication, and Henagliflozin. The choice of hypoglycemic drugs within the background medication is restricted to either one, two, or three among metformin, DPP-4 inhibitors, alpha-glucosidase inhibitors, or secretagogues. |
| Control | Other | Other: Background medicationParticipants in this group will receive lifestyle intervention and background medication. The choice of hypoglycemic drugs within the background medication is restricted to either one, two, or three among metformin, DPP-4 inhibitors, alpha-glucosidase inhibitors, or secretagogues. |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age between 20 and 70 years old.
- Diagnosed with type 2 diabetes according to World Health Organization (WHO) diagnostic criteria, with evidence of fatty liver on ultrasound, and FIB-4 index >1.3.
- Willing to participate in this study and sign an informed consent form. In case the subject lacks the ability to read the informed consent form (e.g., illiterate subjects), the informed process must be witnessed by a designated person who will sign the informed consent form.
- Have not used oral antidiabetic medications or have used one to three oral antidiabetic medications (limited to metformin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, alpha-glucosidase inhibitors, or sulfonylureas) with an HbA1c between 7% and 10%, and fasting venous blood glucose ≤13.3 mmol/L.
- Have not used thiazolidinediones (TZDs), sodium-glucose co-transporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), or other antidiabetic drugs that may affect liver fat content in the last 90 days.
Key exclusion criteria (16 listed)
- Daily alcohol intake of >30 g in the past 10 years or daily alcohol intake of >10 g in the last year.
- History of liver diseases such as hepatitis B, chronic hepatitis C, primary biliary cholangitis (PBC), biliary obstruction disorders, drug-induced liver damage, hemochromatosis, liver cirrhosis, autoimmune hepatitis.
- Patients with decompensated liver cirrhosis, concurrent liver cancer, HIV-positive status, or substance abuse.
- Type 1 diabetes.
- Participation in other clinical trials of diabetes treatment drugs in the 3 months prior to the start of this study.
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 |
|---|---|---|
| HenagliflozinBesides lifestyle intervention and background medication, participants will be prescribed Henagliflozin at standard clinical doses. | Drug | Henagliflozin |
| Background medicationParticipants will only receive lifestyle intervention and background medication. | Other | Control |
Primary outcome
Ultrasound attenuation parameter (UAP)
Time frame: 24 weeks
Changes in ultrasound attenuation parameter (UAP) from baseline. Higher UAP correlates with increased severity of steatosis.
Liver stiffness measurement (LSM)
Time frame: 24 weeks
Changes in liver stiffness measurement (LSM) from baseline. Higher LSM values correlate with advancement in the stage of liver fibrosis.
8 secondary outcomes
Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS)
Time frame: 24 weeks
Fibrosis Index Based on 4 Factors (FIB-4 Index)
Time frame: 24 weeks
Liver fat content
Time frame: 24 weeks
Liver enzymes
Time frame: 24 weeks
Cholestatic proteins (Chitinase 3-like protein 1, CHI3L1)
Time frame: 24 weeks
Intrabdominal fat
Time frame: 24 weeks
Glucose level
Time frame: 24 weeks
Body weight
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
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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.
Jiaqiang Zhou principal investigator
Sir Run Run Shaw Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Henagliflozin and Background medication in people with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, run by Sir Run Run Shaw Hospital.
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 7 inclusion and 16 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 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Yangchi Yang (+86 571 8600 6811, yyc261@foxmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ultrasound attenuation parameter (UAP) (time frame: 24 weeks). 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 23 Jan 2024.