ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes (EmLiFa)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02637973
Recruitment Status : Completed
First Posted : December 22, 2015
Last Update Posted : January 14, 2019
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
German Diabetes Center ( The Deutsche Diabetes Forschungsgesellschaft e.V. )

Brief Summary:
The effects of empagliflozin treatment on hepatocellular lipid content, liver energy metabolism and body composition will be investigated in a multicentre, prospective, placebo-controlled, double-blind, randomized, 2-arm parallel, interventional and exploratory pilot study in patients with newly diagnosed type 2 diabetes.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Non-alcoholic Fatty Liver Disease Drug: Empagliflozin Drug: Placebo Phase 4

Detailed Description:

In this multicentre, prospective, placebo-controlled, double-blind, randomized, 2-arm parallel, interventional pilot study HCL and intramyocellular lipids (IMCL) will be quantified with 1H magnetic resonance (MR) spectroscopy. Hepatic ATP and inorganic phosphate (Pi) concentrations will be assessed with 31P MR spectroscopy (1). Whole-body and hepatic insulin sensitivity and metabolic flexibility will be measured by combining hyperinsulinemic-euglycemic pancreatic clamp tests with isotopic dilution of 6,6-2H2 glucose and indirect calorimetry as shown (2). Abdominal fat distribution will be quantified by MR imaging.

Newly diagnosed patients with type 2 diabetes (T2D) will be randomly allocated to once daily 25 mg empagliflozin (EMPA) or placebo for 24 weeks with a computer-generated random sequence and will be masked to the treatment assignment. Participants will visit the clinical research center at baseline, 12 weeks and 24 weeks for MRS and metabolic examinations, including blood sampling for hepato- and adipocytokines. Anthropometric parameters (body weight, waist circumference, total body fat, blood pressure) and glycemic control (HbA1C, fasting blood glucose, FBG) will be assessed at baseline and during monitoring visits every 4 weeks.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes
Study Start Date : December 2015
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018


Arm Intervention/treatment
Experimental: Empagliflozin
Empagliflozin, film-tablet, 25mg once daily
Drug: Empagliflozin
25 mg once daily
Other Name: Jardiance

Placebo Comparator: Placebo
Placebo, once daily
Drug: Placebo
once daily




Primary Outcome Measures :
  1. Change in liver fat content [ Time Frame: from baseline to 24 weeks ]
    Change in liver fat content between baseline and 24 weeks measured with magnetic resonance spectroscopy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 18 and 75 years
  • BMI<45 kg/m2
  • known diabetes duration up to 7 years
  • 6%≤HbA1c≤8%
  • drug naïve - no previous antihyperglycemic treatment or one month washout period of treatment with oral glucose lowering drugs (no previous treatment with thiazolidinedione (TZD) drugs allowed)
  • obtained written informed consent

Exclusion Criteria:

  • uncontrolled hyperglycaemia at screening (glucose level ≥240 mg/dl after an overnight fast, confirmed by a second measurement)
  • acute coronary syndrome, stroke or transient ischemic attack within 3 months prior to consent
  • previous lower limb amputation
  • severe lower limb infection/ulceration within 3 months prior to consent
  • liver disease 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
  • AST or ALT > 3 x ULN
  • positive result on hepatitis B (HBs-AG), hepatitis C (HCV-AB), or HIV 1 and 2 test
  • impaired kidney function (estimated glomerular filtration rate [eGFR]<60 mL/min/1.73m2) during screening
  • structural and functional urogenital abnormalities, that predispose for urogenital infections
  • gastrointestinal surgeries that induce chronic malabsorption
  • history of cancer (except basal cell carcinoma) or treatment for cancer within 5 years
  • blood dyscrasias or any disorders causing haemolysis or unstable erythrocytes
  • treatment with antiobesity drugs 3 months prior to consent
  • treatment with immunomodulatory drugs (oral steroids, antihistamines)
  • change in dosage of thyroid hormones within 6 weeks of consent
  • pregnancy, lactation period
  • metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible (according to MRT safety checklist in Appendix 11.3)
  • claustrophobia
  • cigarette smoking (non-smoker < 1year), alcohol consumption (male >30 g/d, female >20g/d)
  • drug abuse or psychiatric disease
  • night-worker or circumstances not allowing normal day-night rhythm
  • hypersensitivity to empagliflozin (or drugs of similar chemical structure) or any of the drug compounds
  • pharmaceutical preparations with which interactions can be expected - amiloride, furosemide, indapamide, spironolactone, torasemide, triamterene
  • use of anti-NASH drugs (vitamin E, ursodeoxycholic acid, S-adenosylmethionine, betaine, silymarin, gemfibrozil, anti-TNF therapies, probiotics) in the 3 months prior to randomization
  • women of childbearing potential not using two adequate methods of contraception including a barrier method and a highly efficacious non-barrier method
  • persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • persons held in an institution by legal or official order
  • participation in another trial in the last 10 weeks before randomization or planned participation during the trial period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02637973


Locations
Germany
Charite Universitaetsmedizin Berlin
Berlin, Germany
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Germany, 01307
German Diabetes Center
Dusseldorf, Germany
University Clinic Heidelberg
Heidelberg, Germany
University Clinic Tübingen
Tübingen, Germany
Sponsors and Collaborators
The Deutsche Diabetes Forschungsgesellschaft e.V.
Boehringer Ingelheim

Additional Information:
Responsible Party: The Deutsche Diabetes Forschungsgesellschaft e.V.
ClinicalTrials.gov Identifier: NCT02637973     History of Changes
Other Study ID Numbers: EmLiFa001
First Posted: December 22, 2015    Key Record Dates
Last Update Posted: January 14, 2019
Last Verified: January 2019

Additional relevant MeSH terms:
Empagliflozin
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs