Non-alcoholic Fatty Liver DiseasePhase 4NCT04642261
Effect of Empagliflozin on Liver Fat in Non-diabetic Patients
A Phase 4 study testing Empagliflozin 10 MG in people with Non-alcoholic Fatty Liver Disease, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Empagliflozin 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 98 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jan 2021to 30 Jun 2023
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Potential study subjects will first be screened by transient elastography for the presence of hepatic steatosis (defined as a measurement of controlled attenuation parameter [CAP] >= 248 db/M).
- They will be recruited into study if steatosis is >= 5% as confirmed by MRI-PDFF
Who cannot join
- DM (defined as hemoglobin A1c [HbA1c] >= 6.5% or fasting glucose >= 7.0 mmol/L)
- alcohol intake > 20g within past 2 years
- concurrent chronic liver diseases (including chronic viral hepatitis infection, autoimmune hepatitis, Wilson's disease, hemochromatosis, congestive hepatopathy, primary biliary cholangitis, primary sclerosing cholangitis, biliary tract obstruction)
- drug-induced liver disease
- usage of drugs that can lead to hepatic steatosis (e.g. steroids, amiodarone, valproate, methotrexate, tamoxifen)
- decompensated cirrhosis (including ascites, hepatic hydrothorax, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome)
Show all 11Show fewer
- history of malignancy including HCC
- recreational substance abuse
- pregnancy
- contraindications to empagliflozin use (estimated glomerular filtration rate [eGFR] <45mL/min/1.73m2 as measured by the MDRD equation, history of recurrent genitourinary tract infections, gangrene, or allergy)
- contraindications to MRI (e.g., claustrophobia, certain cardiac pacemakers, implanted medical devices with ferromagnetic properties).
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site
The University of Hong Kong/Queen Mary Hospital
Hong Kong, Hong Kong, China, 852
About this study
Official title: Effect of Empagliflozin on Liver Fat in Non-alcoholic Fatty Liver Disease Patients Without Diabetes Mellitus: a Randomized, Double-blind, Placebo-controlled Trial
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors can reduce hepatic fat content in patients with DM. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and liver stiffness measurement (LSM) are non-invasive methods to diagnose hepatic steatosis and fibrosis/cirrhosis, respectively.
The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of empagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients without DM. A total of 98 adult patients will be randomly sampled from the liver clinic in our local hospital. Empagliflozin 10mg daily will be given to the treatment arm. The placebo pill will be manufactured to be identical in appearance to the study drug. Eligible subjects will be followed up until week 52, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and fasting blood) at baseline, week 6, 12, 26, 40 and 52. They will undergo LSM at baseline, week 26 and 52, and MRI-PDFF at baseline and week 52. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 52 from baseline between the two groups.
The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis in NAFLD patients without DM.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that reduce hepatic fat content in patients with DM, which is independent of glycemic control. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is an emerging non-invasive imaging technique, and is more sensitive than liver biopsy/histology in quantifying liver fat change. Liver stiffness measurement (LSM) by transient elastography is a non-invasive method to diagnose fibrosis/cirrhosis with high accuracy.
The novelty of utilizing the concept of "drug repositioning" by changing the role of SGLT2 inhibitors in treating DM to treating NAFLD in patients without DM deserves exploration. The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of empagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients without DM. A total of 98 adult patients will be randomly sampled from the liver clinical in our local hospital. Empagliflozin 10mg daily will be given to the treatment arm. The placebo pill will be manufactured to be identical in appearance to the study drug. Eligible subjects will be followed up until week 52, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and fasting blood) at baseline, week 6, 12, 26, 40 and 52. They will undergo LSM at baseline, week 26 and 52, and MRI-PDFF at baseline and week 52. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 52 from baseline between the two groups. The secondary outcomes will be remission of steatosis (MRI-PDFF <5%) at week 52, reduction of liver fibrosis (LSM) at week 26 and 52, improvement of laboratory results (including liver transaminases and ductal enzymes, fasting glucose, HbA1c, lipid profile), improvement of anthropometric measurements, and combined cardiovascular and cerebrovascular events.
The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis and regress fibrosis in NAFLD patients without DM.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Empagliflozin 10 MG, Placebo pills
- Keywords
- NAFLD, NASH, fatty liver, empagliflozin, SGLT2 inhibitors
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Also called empagliflozin
Empagliflozin 10mg daily
Placebo pillsDrug
Identical in appearance to empagliflozin 10mg daily
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin group | Experimental | Empagliflozin 10mg daily for 52 weeks Receives: Drug: Empagliflozin 10 MG |
| Placebo group | Placebo comparator | Placebo pills (identical in appearance to empagliflozin 10mg) daily for 52 weeks Receives: Drug: Placebo pills |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fat content
Difference in the change of liver fat content between the two groups at week 52 from the baseline as measured by MRI-PDFF
Measured: week 52
Secondary outcomes (17)
Remission of steatosis
Remission of steatosis (defined as MRI-PDFF < 5%) at week 52
Measured: week 52
Change of liver fat content
Difference in the change of liver fat content between the two groups at week 26 and 52 from the baseline (CAP measured by transient elastography)
Measured: week 26 and 52
Changes of alanine aminotransferase (ALT)
Changes of ALT at week 52
Measured: week 52
Changes of aspartate aminotransferase (AST)
Changes of AST at week 52
Measured: week 52
Changes of alkaline phosphatase (ALP)
Changes of ALP at week 52
Measured: week 52
Changes of gamma glutamyl transferase (GGT)
Changes of GGT at week 52
Measured: week 52
Changes of fasting glucose
Changes of fasting glucose at week 52
Measured: week 52
Changes of haemoglobin A1c (HbA1c)
Changes of HbA1c at week 52
Measured: week 52
Changes of total cholesterol
Changes of total cholesterol at week 52
Measured: week 52
Changes of low density lipoprotein (LDL)
Changes of LDL at week 52
Measured: week 52
Changes of high density lipoprotein (HDL)
Changes of HDL at week 52
Measured: week 52
Changes of body weight
Changes of body weight at week 52
Measured: week 52
Changes of height
Changes of height at week 52
Measured: week 52
Changes of body mass index (BMI)
Changes of BMI at week 52
Measured: week 52
Changes of waist circumference
Changes of waist circumference at week 52
Measured: week 52
Changes of systolic blood pressure
Changes of systolic blood pressure at week 52
Measured: week 52
Changes of diastolic blood pressure
Changes of diastolic blood pressure at week 52
Measured: week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2020
- Study start1 Jan 2021
- Primary completion31 May 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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
- Model description
- Eligible subjects will be randomly allocated to either the empagliflozin group or placebo group (i.e. control group)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Health Bureau, Hong Kong
- Responsible party
- Principal investigator, Cheung Ka Shing, The University of Hong Kong
- Investigators
- Ka Shing Cheung, MD, MPH, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04642261
- Sponsor's protocol ID
- UW 20-065
- Status last verified
- Dec 2023
- First submitted
- 6 Nov 2020
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will be made available in the form of excel files upon request by other researchers
Publications
Cheung KS, Ng HY, Hui RWH, Lam LK, Mak LY, Ho YC, Tan JT, Chan EW, Seto WK, Yuen MF, Leung WK. Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Hepatology. 2024 Oct 1;80(4):916-927. doi: 10.1097/HEP.0000000000000855. Epub 2024 Mar 27.
PubMed 38536017
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Empagliflozin on Liver Fat in Non-alcoholic Fatty Liver Disease Patients Without Diabetes Mellitus: a Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT04642261
- Acronym / sponsor ID
- UW 20-065
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- NAFLD, NASH, fatty liver, empagliflozin, SGLT2 inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Food and Health Bureau, Hong Kong
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 24 Nov 2020 (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.
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors can reduce hepatic fat content in patients with DM. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and liver stiffness measurement (LSM) are non-invasive methods to diagnose hepatic steatosis and fibrosis/cirrhosis, respectively.
The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of empagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients without DM. A total of 98 adult patients will be randomly sampled from the liver clinic in our local hospital. Empagliflozin 10mg daily will be given to the treatment arm. The placebo pill will be manufactured to be identical in appearance to the study drug. Eligible subjects will be followed up until week 52, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and fasting blood) at baseline, week 6, 12, 26, 40 and 52. They will undergo LSM at baseline, week 26 and 52, and MRI-PDFF at baseline and week 52. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 52 from baseline between the two groups.
The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis in NAFLD patients without DM.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is a global epidemic with a prevalence of 25%. Currently therapies for NAFLD patients without diabetes mellitus (DM) are limited, and are associated with various adverse side effects. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that reduce hepatic fat content in patients with DM, which is independent of glycemic control. However, the role of SGLT2 inhibitors in NAFLD patients without DM has not been investigated. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is an emerging non-invasive imaging technique, and is more sensitive than liver biopsy/histology in quantifying liver fat change. Liver stiffness measurement (LSM) by transient elastography is a non-invasive method to diagnose fibrosis/cirrhosis with high accuracy.
The novelty of utilizing the concept of "drug repositioning" by changing the role of SGLT2 inhibitors in treating DM to treating NAFLD in patients without DM deserves exploration. The investigators propose a double-blind, randomized, placebo-controlled trial to compare the effects of empagliflozin (a type of SLGT2 inhibitors) versus placebo (in a 1:1 ratio) in reducing hepatic fat content as measured by MRI-PDFF in NAFLD patients without DM. A total of 98 adult patients will be randomly sampled from the liver clinical in our local hospital. Empagliflozin 10mg daily will be given to the treatment arm. The placebo pill will be manufactured to be identical in appearance to the study drug. Eligible subjects will be followed up until week 52, and will undergo clinical, anthropometric and laboratory assessments (including liver function test and fasting blood) at baseline, week 6, 12, 26, 40 and 52. They will undergo LSM at baseline, week 26 and 52, and MRI-PDFF at baseline and week 52. The primary outcome will be a difference in change of liver fat content (measured by MRI-PDFF) at week 52 from baseline between the two groups. The secondary outcomes will be remission of steatosis (MRI-PDFF <5%) at week 52, reduction of liver fibrosis (LSM) at week 26 and 52, improvement of laboratory results (including liver transaminases and ductal enzymes, fasting glucose, HbA1c, lipid profile), improvement of anthropometric measurements, and combined cardiovascular and cerebrovascular events.
The study results will determine whether SGLT2 inhibitors can reduce hepatic steatosis and regress fibrosis in NAFLD patients without DM.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Eligible subjects will be randomly allocated to either the empagliflozin group or placebo group (i.e. control group)
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin group | Experimental | Drug: Empagliflozin 10 MGEmpagliflozin 10mg daily for 52 weeks |
| Placebo group | Placebo comparator | Drug: Placebo pillsPlacebo pills (identical in appearance to empagliflozin 10mg) daily for 52 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Potential study subjects will first be screened by transient elastography for the presence of hepatic steatosis (defined as a measurement of controlled attenuation parameter [CAP] >= 248 db/M).
- They will be recruited into study if steatosis is >= 5% as confirmed by MRI-PDFF
Key exclusion criteria (11 listed)
- DM (defined as hemoglobin A1c [HbA1c] >= 6.5% or fasting glucose >= 7.0 mmol/L)
- alcohol intake > 20g within past 2 years
- concurrent chronic liver diseases (including chronic viral hepatitis infection, autoimmune hepatitis, Wilson's disease, hemochromatosis, congestive hepatopathy, primary biliary cholangitis, primary sclerosing cholangitis, biliary tract obstruction)
- drug-induced liver disease
- usage of drugs that can lead to hepatic steatosis (e.g. steroids, amiodarone, valproate, methotrexate, tamoxifen)
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 |
|---|---|---|
| Empagliflozin 10 MGAlso: empagliflozinEmpagliflozin 10mg daily | Drug | Empagliflozin group |
| Placebo pillsIdentical in appearance to empagliflozin 10mg daily | Drug | Placebo group |
Primary outcome
Change in liver fat content
Time frame: week 52
Difference in the change of liver fat content between the two groups at week 52 from the baseline as measured by MRI-PDFF
17 secondary outcomes
Remission of steatosis
Time frame: week 52
Change of liver fat content
Time frame: week 26 and 52
Changes of alanine aminotransferase (ALT)
Time frame: week 52
Changes of aspartate aminotransferase (AST)
Time frame: week 52
Changes of alkaline phosphatase (ALP)
Time frame: week 52
Changes of gamma glutamyl transferase (GGT)
Time frame: week 52
Changes of fasting glucose
Time frame: week 52
Changes of haemoglobin A1c (HbA1c)
Time frame: week 52
Changes of total cholesterol
Time frame: week 52
Changes of low density lipoprotein (LDL)
Time frame: week 52
Changes of high density lipoprotein (HDL)
Time frame: week 52
Changes of body weight
Time frame: week 52
Changes of height
Time frame: week 52
Changes of body mass index (BMI)
Time frame: week 52
Changes of waist circumference
Time frame: week 52
Changes of systolic blood pressure
Time frame: week 52
Changes of diastolic blood pressure
Time frame: week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Derived from this study: PubMed 38536017Cheung KS, Ng HY, Hui RWH, Lam LK, Mak LY, Ho YC, Tan JT, Chan EW, Seto WK, Yuen MF, Leung WK. Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Hepatology. 2024 Oct 1;80(4):916-927. doi: 10.1097/HEP.0000000000000855. Epub 2024 Mar 27.
- Individual participant dataSharing planned: No. IPD will be made available in the form of excel files upon request by other researchers
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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.
Ka Shing Cheung, MD, MPH principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 10 MG in people with Non-alcoholic Fatty Liver Disease, run by The University of Hong Kong at 1 site in Hong Kong.
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 2 inclusion and 11 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: finished, as of the sponsor's last update on 7 Dec 2023. 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 Hong Kong. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in liver fat content (time frame: week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04642261, which also lists 1 linked publication.
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 7 Dec 2023.