Combined Active Treatment in Type 2 Diabetes With NASH
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 192
- 试验地点
- 46
- 主要终点
- Histological resolution of NASH without worsening of fibrosis
研究概览
简要总结
The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.
详细描述
Obesity and type 2 diabetes (T2D) are tightly associated with non-alcoholic fatty liver disease (NAFLD), which in turn predicts the development of T2D and cardiovascular disease.
Up to 80% of NAFLD patients with T2D have NASH and the presence of T2D is an independent risk factor for more-advanced fibrosis, higher rate of fibrosis progression, and increased mortality. Liver-related mortality is increased 10-fold in NASH patients compared with the general population. In addition, people with NASH are at an excessive risk of cardiovascular morbidity and mortality.
Currently, there are no established pharmacotherapies for NASH patients with T2D.
The aim of this trial is to evaluate efficacy of a combined treatment with semaglutide 1 mg/week (GLP1RA) and empagliflozin 10 mg/d (SGLT2I) or ii) empagliflozin 10 mg/d monotherapy by means of histological resolution of NASH in T2D patients without progression of fibrosis after 48 weeks treatment.
To confirm a histological diagnosis of NASH and proof efficacy of treatment, a liver biopsy will be performed prior to screening as well as at the end of treatment phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double-blind placebo-controlled
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of T2D and NASH with fibrosis stage F1-F3
- •Age between 25 and 75 years
- •HbA1c ≤ 9.5%
- •obtained written informed consent
排除标准
- •Contraindications on liver biopsy
- •Evidence of cirrhosis on liver biopsy
- •Liver disease of other etiology including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology
- •History of ketoacidosis
- •Alcohol consumption >30 g/d for males and >20 g/d for females
- •Past (≥5 years) or current history of alcohol or drug abuse and/or psychiatric disease including severe depression necessitating pharmacological treatment
- •Medications that may induce steatosis:tamoxifen, raloxifene, oral glucocorticoids or chloroquine
- •Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method
研究组 & 干预措施
Combined treatment with Empagliflozin and Semaglutide
Combined treatment with Empagliflozin, film-coated tablet, 10mg once daily and Semaglutide, colourless solution in pre-filled pen, 1mg once weekly
干预措施: Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector (Drug)
Empagliflozin monotherapy
Empagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)
干预措施: Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide (Drug)
Placebo
Placebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)
干预措施: Placebo matching empagliflozin and placebo pen injector matching semaglutide (Drug)
结局指标
主要结局
Histological resolution of NASH without worsening of fibrosis
时间窗: from baseline to 48 weeks
NAFLD status will be assessed by histologic evaluation of liver biopsy samples based on NAFLD activity score. NASH resolution is defined by disappearance of ballooning (score 0), together with either disappearance of lobular inflammation or the persistence of mild lobular inflammation only (score 0 or 1) and resulting in an overall pathologic diagnosis of either steatosis alone or steatosis with mild inflammation; with no worsening of fibrosis. Worsening of fibrosis is defined by an increase of at least one stage of the Kleiner fibrosis classification.
次要结局
- Overall NAFLD activity score (NAS)(from baseline to 48 weeks)
- Stage of fibrosis according to the Kleiner Fibrosis Classification(from baseline to 48 weeks)
- Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score(from baseline to 48 weeks)
- Hepatic steatosis grade(from baseline to 48 weeks)