Clinical trial NCT04639414: Combined Active Treatment in Type 2 Diabetes with NASH
Official title: Combined Active Treatment in Type 2 Diabetes with NASH
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Type 2 Diabetes
Non-alcoholic Steatohepatitis (NASH)
Non-alcoholic Fatty Liver Disease (NAFLD)
Keywords: Type 2 Diabetes
Non-alcoholic Steatohepatitis (NASH)
Non-alcoholic Fatty Liver Disease (NAFLD)
Fatty liver
Diabetes mellitus
Empagliflozin
Semaglutide
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: German Center for Diabetes Research
name: Federal Ministry of Health, Germany
name: Ministry of Innovation, Science and Research in North Rhine-Westphalia
name: Novo Nordisk A/S
First posted: 2020-11-20
Enrollment: 192
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of T2D and NASH with fibrosis stage F1-F3
* Age between 25 and 75 years
* HbA1c ≤ 9.5%
* obtained written informed consent

Exclusion Criteria:

* 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

Primary outcomes:
measure: Histological resolution of NASH without worsening of fibrosis
timeFrame: from baseline to 48 weeks
Secondary outcomes:
measure: Overall NAFLD activity score (NAS)
timeFrame: from baseline to 48 weeks
measure: Stage of fibrosis according to the Kleiner Fibrosis Classification
timeFrame: from baseline to 48 weeks
measure: Activity component of NASH according to the steatosis-activity-fibrosis (SAF) score
timeFrame: from baseline to 48 weeks
measure: Hepatic steatosis grade
timeFrame: from baseline to 48 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Wiener Gesundheitsverbund, Klinik Landstraße
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Wien
country: Austria
facility: Wiener Gesundheitsverbund, Klinik Hietzing
city: Duesseldorf
country: Germany
facility: German Diabetes Center
state: Nordrhein-Westfalen
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Berlin
country: Germany
facility: Franziskus-Krankenhaus Berlin
city: Berlin
country: Germany
facility: Leber- und Studienzentrum Checkpoint
city: Berlin
country: Germany
facility: University Clinics Berlin Charité
city: Berlin
country: Germany
facility: University Clinics Berlin Charité
city: Bochum
country: Germany
facility: University Clinics Bochum
city: Brandenburg
country: Germany
facility: Städtisches Klinikum Brandenburg GmbH
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH
city: Dresden
country: Germany
facility: University Clinics Carl Gustav Carus Dresden
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: University Clinics Essen
city: Frankfurt
country: Germany
facility: University Clinics Frankfurt
city: Freiburg
country: Germany
facility: University Clinics Freiburg
city: Heidelberg
country: Germany
facility: University Clinics Heidelberg
city: Leipzig
country: Germany
facility: Eugastro GmbH
city: Mainz
country: Germany
facility: University Clinics Johannes-Gutenberg Mainz
city: München
country: Germany
facility: TUM
city: Tübingen
country: Germany
facility: University Clinics Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Würzburg
country: Germany
facility: University Clinics Würzburg
Study officials:
affiliation: German Diabetes Center
name: Michael Roden, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: