Clinical trial NCT03723252: Dapagliflozin Efficacy and Action in NASH
Official title: Efficacy and Safety of Dapagliflozin in Non-alcoholic Steatohepatitis: a Multicentre, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nonalcoholic Steatohepatitis
Keywords: Nonalcoholic Steatohepatitis
SGLT-2 inhibitor
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2018-10-29
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Improvement in scored liver histological improvement over 12 months
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Resolution of NASH
timeFrame: Baseline to 12 months
measure: Improvement of fibrosis
timeFrame: Baseline to 12 months
measure: Change in fibrosis score
timeFrame: Baseline to 12 months
measure: Change in each component score in the NAS
timeFrame: Baseline to 12 months
measure: Change in body weight
timeFrame: Baseline to 12 months
measure: Change in waist circumference
timeFrame: Baseline to 12 months
measure: Change in visceral fat
timeFrame: Baseline to 12 months
measure: Change in liver fat
timeFrame: Baseline to 12 months
measure: Change in HbA1C
timeFrame: Baseline to 12 months
measure: Change in blood pressure
timeFrame: Baseline to 12 months
measure: Change in serum lipids
timeFrame: Baseline to 12 months
measure: Change in insulin resistance
timeFrame: Baseline to 12 months
measure: Change in inflammatory markers of NASH
timeFrame: Baseline to 12 months
measure: Change in health related quality of life scores (SF-36)
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Huijie Zhang, MD.PhD.
role: PRINCIPAL_INVESTIGATOR
References: