Dapagliflozin Efficacy and Action in NASH

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy and Safety of Dapagliflozin in Non-alcoholic Steatohepatitis: a Multicentre, Randomized, Placebo-controlled Trial

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Significant alcohol consumption in the past six months (Consumed more than 20 g/day for women or 30 g/day for men); A history of alcoholic liver disease, chronic viral hepatitis, drug-induced hepatitis, autoimmune hepatitis, cirrhosis, and liver cancer; Obstructive biliary disease; Having any medical condition that would affect metabolism (i.e. Cushing syndrome, known hyperthyroidism or hypothyroidism); 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); Taking any medication (i.e. cortisol, methotrexate)that would affect steatohepatitis for more than two weeks in the past year; Chronic kidney disease or severe impaired renal function (serum creatinine≥ 2.0mg/dl); Serum alanine aminotransferase (ALT) greater than 300U/L A history of Type 1 diabetes; A history of bladder cancer; Women who are pregnant or plan to become pregnant; Serious medical disease with likely life expectancy less than 5 years; Patients who cannot be followed for 24 months (due to a health situation or migration); Participation in other clinical trial in the 30 days before randomization; Patients who are unwilling or unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin group<br>Participants will receive dapagliflozin 10mg po qd. | Drug: Dapagliflozin<br>* Participants will receive dapagliflozin 10mg po qd<br>|
| Placebo Comparator: Placebo group<br>Participants will receive placebo po qd. | Drug: Placebo<br>* Participants will receive placebo po qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in scored liver histological improvement over 12 months |  | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of NASH |  | Baseline to 12 months | 
| 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 | 
| Change in liver fat |  | Baseline to 12 months | 
| 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-12) |  | Baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonalcoholic Steatohepatitis, SGLT-2 inhibitor