Non-alcoholic SteatohepatitisPhase 2NCT05254626
Efficacy and Safety of Dapagliflozin in Patients with Non-alcoholic Steatohepatitis
A Phase 2 study testing Dapagliflozin 10Mg Tab and Pioglitazone 30 mg in people with Non-alcoholic Steatohepatitis, run by Cairo University at 1 site in Egypt.
Trial summary
Patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of more aggressive liver disease; non-alcoholic steatohepatitis (NASH) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular diseases. NAFLD is spreading as an epidemic in patients with metabolic syndrome. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-alcoholic Steatohepatitis
- What is being tested?
- Dapagliflozin 10Mg Tab and Pioglitazone 30 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2022to 23 Jul 2024
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age range 18-65 years.
- Liver biopsy confirming NASH within 6 months.
- For diabetic patients, the patients should be with stable glycemic control defined as HbA1C <10%.
Who cannot join
- Active viral hepatitis (HBV, HCV).
- Child Pugh B or C cirrhosis.
- Alcohol consumption in the past six months.
- A history of alcoholic liver disease.
- Secondary causes of steatohepatitis.
- Autoimmune hepatitis.
Show all 24Show fewer
- Celiac disease.
- Hemochromatosis or Wilson's disease.
- Drug induced liver injury (DILI) or patient with history of taking medication(s) that may cause fatty liver (e.g., tamoxifen, valproic acid, amiodarone, methotrexate, steroids, oral contraceptives).
- Obstructive biliary disease.
- Serum alanine aminotransferase (ALT) more than 2.5 folds of UNL.
- History of serious hypersensitivity to dapagliflozin or pioglitazone or any component of the formulation.
- Pregnancy and breastfeeding.
- Renal impairment (eGFR <45 mL/minute/1.73 m2), end-stage renal disease (ESRD), or patients on dialysis.
- Having any medical condition that would affect metabolism (i.e., known hyperthyroidism or hypothyroidism).
- Hypopituitarism.
- Patients with Type 1 diabetes.
- Starvation.
- Serious medical disease with likely life expectancy less than 5 years.
- Participation in other clinical trial in the 30 days before enrollment.
- Patients who are unwilling or unable to give informed consent.
- Patients on statins.
- Heart failure defined as New York Heart Association (NYHA) class III or IV.
- Recent initiation or change of antidiabetic drugs that influence liver fat including thiazolidinediones, glucagon like peptide 1 receptor agonists or any SGLT2 inhibitor.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
National Hepatology and Tropical Medicine Research Institute
Cairo, Cairo Governorate
About this study
Official title: Efficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-diabetic Patients with Non-alcoholic Steatohepatitis
Patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of more aggressive liver disease; non-alcoholic steatohepatitis (NASH) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular diseases. NAFLD is spreading as an epidemic in patients with metabolic syndrome. Its components include obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The prevalence of NAFLD is likely to increase resulting in tremendous clinical, social and economic burdens. Unfortunately, there is no approved medication to treat patients with NASH-induced advanced fibrosis. Weight management is the first line of NASH treatment even in non-obese patients with at least 7% reduction of patient's weight. However, NASH patients need pharmacological treatment. Sodium glucose co-transporter (SGLT2) inhibitors demonstrated favorable effects on NAFLD without weight gain as an adverse event proposed by pioglitazone used for the same indication. SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with or without T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of body weight and hyperglycemia in patients with or without diabetes.
This study aims to evaluate the efficacy and safety of SGLT2 inhibitors in NASH patients in comparison to pioglitazone.
Read more
This is a randomized prospective parallel study, where all patients presented with NASH to the outpatient clinic in the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; will be screened for specific inclusion and exclusion criteria. Diabetic and non-diabetic patients will be randomly assigned to receive one of two treatment modalities. The first arm will be the NASH patients receiving dapagliflozin and the second arm will be the NASH patients receiving pioglitazone for 24 weeks. Each group will have an equal number of diabetic and non-diabetic patients.
All patients will be assessed for body composition, serum creatinine level, fasting blood glucose level, HbA1C, markers of insulin resistance (HOMA-IR), complete blood count, serum liver function tests, and NAFLD fibrosis score (NAS). Liver biopsy will be performed at baseline and at the end of the study and the total NAS score will be calculated. All patients will be assessed for any adverse drug reactions, and for their adherence by pill count method. Also, quality of life will be assessed for all patients using previously designed and validated questionnaire called Chronic Liver Disease Questionnaire (CLDQ).
- Conditions
- Non-alcoholic Steatohepatitis
- Being tested
- Dapagliflozin 10Mg Tab, Pioglitazone 30 mg
- Keywords
- Dapagliflozin, SGLT2 inhibitors, NASH, Efficacy, Safety, Liver biopsy, Pioglitazone, Fatty Liver, NAFLD activity score
- 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.
Dapagliflozin 10Mg TabDrug
Dapagliflozin 10 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; in comparison to pioglitazone.
Pioglitazone 30 mgDrug
Pioglitazone 30 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; as an active control and standard of care treatment.
| Study group | Role | What they receive |
|---|---|---|
| Diabetic Group 1 | Experimental | 25 diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks Receives: Drug: Dapagliflozin 10Mg Tab |
| Diabetic Group 2 | Active comparator | 25 diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks Receives: Drug: Pioglitazone 30 mg |
| Non-diabetic Group 1 | Experimental | 25 non-diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks. Receives: Drug: Dapagliflozin 10Mg Tab |
| Non-diabetic Group 2 | Active comparator | 25 non-diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks Receives: Drug: Pioglitazone 30 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histological Features (Liver Biopsy)
Change from baseline of NAFLD Activity Score (NAS) and other histological features. NAS score will be assessed using the NASH Clinical Research Network (NASH CRN) scoring system. NAS score ranges from 0 to 8 and the higher score towards 8 means worse outcome.
Measured: Baseline and 24th week
Secondary outcomes (16)
NAFLD fibrosis score
Change in NAFLD fibrosis score (NFS). The score ranges from < -1.45 (no significant fibrosis) to > 0.67 (significant fibrosis). The higher score means worse outcome.
Measured: Baseline and 24th week
Fibrosis Index Based on 4 factors
Change in Fibrosis Index Based on 4 factors (FIB-4). The score ranges from < 1.45 (minimal to no fibrosis) to > 3.4 (advanced fibrosis). The higher score means worse outcome.
Measured: Baseline and 24th week
Fibro-controlled attenuated parameter (fibro CAP)
Improvement of fibro-controlled attenuated parameter (fibro CAP)
Measured: Baseline and 24th week
Serum Alanine Transaminase level (ALT)
Change in ALT serum level as inflammatory markers of NASH
Measured: Baseline, 12th and 24th week
Serum Aspartate Aminotransferase level (AST)
Change in AST serum level as inflammatory markers of NASH
Measured: Baseline, 12th and 24th week
Serum Alkaline Phosphatase level (ALP)
Change in ALP serum level as inflammatory markers of NASH
Measured: Baseline, 12th and 24th week
Serum Gamma-glutamyl Transferase level (GGT)
Change in GGT serum level as inflammatory markers of NASH
Measured: Baseline, 12th and 24th week
Serum total and direct bilirubin.
Change in levels of serum total and direct bilirubin.
Measured: Baseline, 12th and 24th week
Waist circumference
Change in waist circumference
Measured: Baseline, 3rd, 6th, 12th, 18th and 24th week
Body weight
Change in body weight
Measured: Baseline, 3rd, 6th, 12th, 18th and 24th week
Lipid profile
Change in serum lipids
Measured: Baseline, 12th and 24th week
Glycated hemoglobin (HbA1C)
Change in HbA1C level for patients with T2DM
Measured: Baseline, 12th and 24th week
Fasting blood glucose level
Change in fasting blood glucose for patients with T2DM
Measured: Baseline, 3rd, 6th, 12th, 18th and 24th week
Insulin resistance (HOMA-IR)
Measured: Baseline, 12th and 24th week
Quality of life Questionnaire (quality of life assessment)
Change in health-related quality of life scores using chronic liver disease questionnaire (CLDQ)
Measured: Baseline and 24th week
Drugs adverse events
Assessment of safety by reporting any adverse events
Measured: Baseline, 3rd, 6th, 12th, 18th and 24th week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2022
- Study start1 Aug 2022
- Primary completion23 Jan 2024
- Study completion23 Jul 2024
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 SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Cairo 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nirmeen Ahmed Sabry, Cairo University
- Investigators
- Nirmeen A. Sabry, Principal investigator, Clinical Pharmacy Department - Faculty of Pharmacy - Cairo university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05254626
- Sponsor's protocol ID
- CL (3148)
- Status last verified
- Sep 2024
- First submitted
- 1 Dec 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abdel Monem MS, Adel A, Abbassi MM, Abdelaziz DH, Hassany M, Raziky ME, Sabry NA. Efficacy and safety of dapagliflozin compared to pioglitazone in diabetic and non-diabetic patients with non-alcoholic steatohepatitis: A randomized clinical trial. Clin Res Hepatol Gastroenterol. 2025 Mar;49(3):102543. doi: 10.1016/j.clinre.2025.102543. Epub 2025 Jan 29.
PubMed 39884573
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-diabetic Patients with Non-alcoholic Steatohepatitis
- ClinicalTrials.gov ID
- NCT05254626
- Acronym / sponsor ID
- CL (3148)
- Conditions
- Non-alcoholic Steatohepatitis
- Keywords
- Dapagliflozin, SGLT2 inhibitors, NASH, Efficacy, Safety, Liver biopsy, Pioglitazone, Fatty Liver
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 23 Jan 2024 (actual)
- Study completion
- 23 Jul 2024 (actual)
- First posted
- 24 Feb 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.
Patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of more aggressive liver disease; non-alcoholic steatohepatitis (NASH) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular diseases. NAFLD is spreading as an epidemic in patients with metabolic syndrome. Its components include obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The prevalence of NAFLD is likely to increase resulting in tremendous clinical, social and economic burdens. Unfortunately, there is no approved medication to treat patients with NASH-induced advanced fibrosis. Weight management is the first line of NASH treatment even in non-obese patients with at least 7% reduction of patient's weight. However, NASH patients need pharmacological treatment. Sodium glucose co-transporter (SGLT2) inhibitors demonstrated favorable effects on NAFLD without weight gain as an adverse event proposed by pioglitazone used for the same indication. SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with or without T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of body weight and hyperglycemia in patients with or without diabetes.
This study aims to evaluate the efficacy and safety of SGLT2 inhibitors in NASH patients in comparison to pioglitazone.
This is a randomized prospective parallel study, where all patients presented with NASH to the outpatient clinic in the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; will be screened for specific inclusion and exclusion criteria. Diabetic and non-diabetic patients will be randomly assigned to receive one of two treatment modalities. The first arm will be the NASH patients receiving dapagliflozin and the second arm will be the NASH patients receiving pioglitazone for 24 weeks. Each group will have an equal number of diabetic and non-diabetic patients.
All patients will be assessed for body composition, serum creatinine level, fasting blood glucose level, HbA1C, markers of insulin resistance (HOMA-IR), complete blood count, serum liver function tests, and NAFLD fibrosis score (NAS). Liver biopsy will be performed at baseline and at the end of the study and the total NAS score will be calculated. All patients will be assessed for any adverse drug reactions, and for their adherence by pill count method. Also, quality of life will be assessed for all patients using previously designed and validated questionnaire called Chronic Liver Disease Questionnaire (CLDQ).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Diabetic Group 1 | Experimental | Drug: Dapagliflozin 10Mg Tab25 diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks |
| Diabetic Group 2 | Active comparator | Drug: Pioglitazone 30 mg25 diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks |
| Non-diabetic Group 1 | Experimental | Drug: Dapagliflozin 10Mg Tab25 non-diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks. |
| Non-diabetic Group 2 | Active comparator | Drug: Pioglitazone 30 mg25 non-diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age range 18-65 years.
- Liver biopsy confirming NASH within 6 months.
- For diabetic patients, the patients should be with stable glycemic control defined as HbA1C <10%.
Key exclusion criteria (24 listed)
- Active viral hepatitis (HBV, HCV).
- Child Pugh B or C cirrhosis.
- Alcohol consumption in the past six months.
- A history of alcoholic liver disease.
- Secondary causes of steatohepatitis.
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 |
|---|---|---|
| Dapagliflozin 10Mg TabDapagliflozin 10 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; in comparison to pioglitazone. | Drug | Diabetic Group 1, Non-diabetic Group 1 |
| Pioglitazone 30 mgPioglitazone 30 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; as an active control and standard of care treatment. | Drug | Diabetic Group 2, Non-diabetic Group 2 |
Primary outcome
Histological Features (Liver Biopsy)
Time frame: Baseline and 24th week
Change from baseline of NAFLD Activity Score (NAS) and other histological features. NAS score will be assessed using the NASH Clinical Research Network (NASH CRN) scoring system. NAS score ranges from 0 to 8 and the higher score towards 8 means worse outcome.
16 secondary outcomes
NAFLD fibrosis score
Time frame: Baseline and 24th week
Fibrosis Index Based on 4 factors
Time frame: Baseline and 24th week
Fibro-controlled attenuated parameter (fibro CAP)
Time frame: Baseline and 24th week
Serum Alanine Transaminase level (ALT)
Time frame: Baseline, 12th and 24th week
Serum Aspartate Aminotransferase level (AST)
Time frame: Baseline, 12th and 24th week
Serum Alkaline Phosphatase level (ALP)
Time frame: Baseline, 12th and 24th week
Serum Gamma-glutamyl Transferase level (GGT)
Time frame: Baseline, 12th and 24th week
Serum total and direct bilirubin.
Time frame: Baseline, 12th and 24th week
Waist circumference
Time frame: Baseline, 3rd, 6th, 12th, 18th and 24th week
Body weight
Time frame: Baseline, 3rd, 6th, 12th, 18th and 24th week
Lipid profile
Time frame: Baseline, 12th and 24th week
Glycated hemoglobin (HbA1C)
Time frame: Baseline, 12th and 24th week
Fasting blood glucose level
Time frame: Baseline, 3rd, 6th, 12th, 18th and 24th week
Insulin resistance (HOMA-IR)
Time frame: Baseline, 12th and 24th week
Quality of life Questionnaire (quality of life assessment)
Time frame: Baseline and 24th week
Drugs adverse events
Time frame: Baseline, 3rd, 6th, 12th, 18th and 24th week
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 19 Sep 2024.
- Derived from this study: PubMed 39884573Abdel Monem MS, Adel A, Abbassi MM, Abdelaziz DH, Hassany M, Raziky ME, Sabry NA. Efficacy and safety of dapagliflozin compared to pioglitazone in diabetic and non-diabetic patients with non-alcoholic steatohepatitis: A randomized clinical trial. Clin Res Hepatol Gastroenterol. 2025 Mar;49(3):102543. doi: 10.1016/j.clinre.2025.102543. Epub 2025 Jan 29.
- Individual participant dataSharing planned: No
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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.
Nirmeen A. Sabry principal investigator
Clinical Pharmacy Department - Faculty of Pharmacy - Cairo university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin 10Mg Tab and Pioglitazone 30 mg in people with Non-alcoholic Steatohepatitis, run by Cairo University at 1 site in Egypt.
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 3 inclusion and 24 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 19 Sep 2024. 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 Egypt. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Histological Features (Liver Biopsy) (time frame: Baseline and 24th week). 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 NCT05254626, 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 19 Sep 2024.