Nonalcoholic Steatohepatitis
Conditions
Keywords
Nonalcoholic Steatohepatitis, SGLT-2 inhibitor
Brief summary
This is a multicentre, randomized, placebo-controlled trial to assess the efficacy and safety of dapagliflozin on improving non-alcoholic steatohepatitis as determined by liver biopsies and metabolic risk factors.
Interventions
DRUGDapagliflozin
Participants will receive dapagliflozin 10mg po qd
DRUGPlacebo
Participants will receive placebo po qd
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women aged≥18 years; * Non-alcoholic steatohepatitis as determined by liver biopsies within 6 months; * Patients with T2DM at screening had to have stable glycaemic control (HbA1c \<9.5%) .
Exclusion criteria
1. Significant alcohol consumption in the past six months (Consumed more than 20 g/day for women or 30 g/day for men); 2. A history of alcoholic liver disease, chronic viral hepatitis, drug-induced hepatitis, autoimmune hepatitis, cirrhosis, and liver cancer; 3. Obstructive biliary disease; 4. Having any medical condition that would affect metabolism (i.e. Cushing syndrome, known hyperthyroidism or hypothyroidism); 5. Poor glucose control (defined as HbA1C≤ 9.5% within 3 months) if diagnosed with T2DM, or taking any antidiabetic medication that would affect metabolism or weight loss (i.e. TZD, GLP-1, DPP-4i or initially using insulin in the past 3 months); 6. Taking any medication (i.e. cortisol, methotrexate)that would affect steatohepatitis for more than two weeks in the past year; 7. Chronic kidney disease or severe impaired renal function (serum creatinine≥ 2.0mg/dl); 8. Serum alanine aminotransferase (ALT) greater than 300U/L 9. A history of Type 1 diabetes; 10. A history of bladder cancer; 11. Women who are pregnant or plan to become pregnant; 12. Serious medical disease with likely life expectancy less than 5 years; 13. Patients who cannot be followed for 24 months (due to a health situation or migration); 14. Participation in other clinical trial in the 30 days before randomization; 15. Patients who are unwilling or unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement in scored liver histological improvement over 12 months | Baseline to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of fibrosis | Baseline to 12 months | defined as reduction in fibrosis of at least 1 stage) without worsening of NASH |
| Change in fibrosis score | Baseline to 12 months | — |
| Change in each component score in the NAS | Baseline to 12 months | — |
| Change in body weight | Baseline to 12 months | — |
| Change in waist circumference | Baseline to 12 months | — |
| Change in visceral fat | Baseline to 12 months | — |
| Resolution of NASH | Baseline to 12 months | defined as a hepatocellular ballooning score of 0, and lobular inflammation score of 0 or 1) without worsening of fibrosis |
| Change in HbA1C | Baseline to 12 months | — |
| Change in blood pressure | Baseline to 12 months | — |
| Change in serum lipids | Baseline to 12 months | — |
| Change in insulin resistance | Baseline to 12 months | — |
| Change in inflammatory markers of NASH | Baseline to 12 months | — |
| Change in health related quality of life scores (SF-36) | Baseline to 12 months | — |
| Change in liver fat | Baseline to 12 months | — |
Countries
China
Outcome results
None listed