COMBAT T2 NASH

This study investigates whether combination therapy with empagliflozin and semaglutide or therapy with empagliflozin alone leads to a regression of non-alcoholic steatohepatitis (NASH) and at the same time prevents the progression of liver fibrosis.

The study is planned to be conducted at 40 locations across Germany.

Background of the study

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease of type 2 diabetes mellitus. Clinical studies have shown that diabetic patients with NAFLD have an increased risk of cardiovascular disease, chronic kidney disease and diabetic neuropathy.
NAFLD is characterized by an excessive accumulation of fat in the liver cells. In addition, patients with type 2 diabetes in particular have an increased risk of the disease progressing to non-alcoholic steatohepatitis (NASH), dynamic connective tissue remodeling of the liver tissue (fibrosis; end stage: cirrhosis) with potential liver failure, and the development of liver cell carcinoma. NASH is characterized by a build-up of excess fat in the liver, accompanied by inflammation in the liver tissue.
NASH is currently not treated with targeted drugs, but rather with lifestyle changes aimed at weight loss. However, research suggests that drugs that are effective for type 2 diabetes may also have a beneficial effect on NAFLD.
In the COMBAT T2 NASH study, the active substances empagliflozin (Jardiance®) and semaglutide (Ozempic®), which are already approved for the treatment of type 2 diabetes in Germany, will be compared with a placebo (i.e. tablets or injection liquid that contain no active substance) in order to examine their effectiveness on NASH. The study will investigate whether combination therapy with empagliflozin and semaglutide or therapy with empagliflozin alone leads to a regression of NASH and at the same time prevents the progression of liver fibrosis.
The treatment with the above-mentioned drugs supports the blood glucose control of your diabetes and could at the same time contribute to the regression or non-progression of NAFLD and other diabetes-related complications.   

 

Eligible participants   

  • Men and women between the ages of 25 and 75
  • Diagnosed type 2 diabetes
  • Suspected or diagnosed non-alcoholic steatohepatitis (NASH)
  • BMI ≤45 kg/m2

 

Key exclusion criteria

  • Age under 25 or over 75 years
  • Contraindications for liver biopsy
  • No evidence of liver fibrosis
  • Previous diabetic ketoacidosis
  • High alcohol consumption
  • Liver diseases due to other causes (e.g. chronic viral hepatitis (B or C), alcohol abuse, liver cirrhosis
  • Use of certain drugs (e.g. pioglitazone therapy within the last 12 months, tamoxifen, raloxifene, oral glucocorticosteroids, chloroquine, methotrexate, amiodarone, biologicals)
  • Planned pregnancy, pregnant or breastfeeding women
  • Addictions such as alcohol or drug abuse

 

Study procedure

In total, the study comprises around 18 visits to the study center lasting several hours.
At the beginning and after the end of the drug treatment phase, you will have a liver biopsy (removal  of tissue from the liver through the skin using a thin needle), performed as an outpatient procedure. The first liver biopsy is used to confirm NASH and liver fibrosis and checks whether you meet all inclusion criteria for participation in the study. The second liver biopsy will be conducted to determine whether there has been any change or, if possible, an improvement in your liver disease compared to when you started your participation in the study.
The drug treatment phase lasts 48 weeks and involves taking a daily tablet and having a weekly injection under the skin. During this phase you must come to the study center once a month to have your blood values checked, among other things.
In certain cases it may be necessary, in consultation with your study physician, to suspend or change your previous diabetes medication for the duration of the study participation.
During the entire duration of the study, you will be asked to measure your blood glucose at least once a day and to keep a blood glucose diary.
Participation in the study will take around 15 months in total. 

 

Medical tests and examinations

  • Medical physical examination
  • Body measurements (weight, height, abdominal and waist circumference)
  • Measurement of vital signs (i.e. blood pressure, pulse, body temperature)
  • Electrocardiogram (ECG)
  • Blood and urine tests
  • Ultrasound scan of your liver
  • Elastography measurement of the liver using FibroScan® (special ultrasound technology; depending on the equipment of your study center)
  • Screening of the liver in an MRI scanner to measure your liver fat content and to determine liver stiffness (depending on the equipment of your study center)
  • Mixed-Meal Test (MMT) to assess the insulin sensitivity of body cells as well as the insulin secretion of special cells of the pancreas
  • Recording of eating habits, alcohol consumption and quality of life using questionnaires

 

Reimbursement of expenses

All examinations are free of charge for you – the study center bears the costs. You will receive a financial allowance for participating in the examinations during the study visits as well as a reimbursement of your travel costs to the study center. 

 

Participating Clinics:

Berlin/Potsdam
Prof. Andreas Pfeiffer
German Institute of Human Nutrition /
Charité Berlin
Phone: 033200–882778 or 882774
gesund.leben(at)dife.de


Düsseldorf
PD Dr.  Julia Szendrödi
German Diabetes Center
Phone: 0211–3382209
studienzentrum(at)ddz.de


Dresden
Study Center Dresden
studien-stoffwechsel(at)ukdd.de


Heidelberg
Prof. Peter Nawroth
Heidelberg University Hospital
Phone: 06221 56-8606
DZD.Studien(at)med.uni-heidelberg.de 


München
Prof. Jochen Seißler, Dr. Andreas Lechner
Ludwig-Maximilians-University
Phone: 089–4400–52234


Tübingen
Prof. Andreas Fritsche, Prof. Norbert Stefan,
Tübingen University Hospital
Phone: 07071–2980687