Combined Active Treatment in Type 2 Diabetes with NASH

NCT ID: NCT04639414

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-26
• Study Completion Date: 2025-12-31

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.

Conditions

Type 2 Diabetes; Non-alcoholic Steatohepatitis (NASH); Non-alcoholic Fatty Liver Disease (NAFLD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector

Intervention Type: DRUG

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d compared to matching placebo after 48-week treatment.

Empagliflozin monotherapy

Empagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Group Type: EXPERIMENTAL

Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide

Intervention Type: DRUG

Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Placebo

Placebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Group Type: PLACEBO_COMPARATOR

Placebo matching empagliflozin and placebo pen injector matching semaglutide

Intervention Type: DRUG

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d OR empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Interventions

Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d compared to matching placebo after 48-week treatment.

Intervention Type: DRUG

Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide

Measurement of the effect of empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Intervention Type: DRUG

Placebo matching empagliflozin and placebo pen injector matching semaglutide

Measurement of the effect of the combined treatment with semaglutide 1mg/week and empagliflozin 10 mg/d OR empagliflozin monotherapy 10mg/d compared to matching placebo after 48-week treatment.

Intervention Type: DRUG

Other Intervention Names

Jardiance(R), Ozempic(R); Jardiance(R); Control / Placebo

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

German Center for Diabetes Research

OTHER

Sponsor Role: collaborator

Federal Ministry of Health, Germany

OTHER_GOV

Sponsor Role: collaborator

Ministry of Innovation, Science and Research in North Rhine-Westphalia

UNKNOWN

Sponsor Role: collaborator

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

German Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Roden, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

German Diabetes Center

Locations

Medizinische Universität Graz

Graz, , Austria

Medizinische Universität Innsbruck

Innsbruck, , Austria

Wiener Gesundheitsverbund, Klinik Landstraße

Vienna, , Austria

Medizinische Universität Wien

Vienna, , Austria

Wiener Gesundheitsverbund, Klinik Hietzing

Vienna, , Austria

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, Germany

Herz- und Diabeteszentrum NRW

Bad Oeynhausen, , Germany

Franziskus-Krankenhaus Berlin

Berlin, , Germany

Leber- und Studienzentrum Checkpoint

Berlin, , Germany

University Clinics Berlin Charité

Berlin, , Germany

University Clinics Berlin Charité

Berlin, , Germany

University Clinics Bochum

Bochum, , Germany

Städtisches Klinikum Brandenburg GmbH

Brandenburg, , Germany

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, , Germany

University Clinics Carl Gustav Carus Dresden

Dresden, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

University Clinics Essen

Essen, , Germany

University Clinics Frankfurt

Frankfurt, , Germany

University Clinics Freiburg

Freiburg im Breisgau, , Germany

University Clinics Heidelberg

Heidelberg, , Germany

Eugastro GmbH

Leipzig, , Germany

University Clinics Johannes-Gutenberg Mainz

Mainz, , Germany

TUM

München, , Germany

University Clinics Tübingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

University Clinics Würzburg

Würzburg, , Germany

Countries

Austria; Germany

Other Identifiers

2019-001987-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Combat_T2_NASH_002

Identifier Type: -

Identifier Source: org_study_id