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

Primary Purpose

Type 2 Diabetes, Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Empagliflozin
Placebo
Sponsored by
The Deutsche Diabetes Forschungsgesellschaft e.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Charite Universitaetsmedizin Berlin
  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
  • German Diabetes Center
  • University Clinic Heidelberg
  • University Clinic Tübingen

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Empagliflozin

Placebo

Arm Description

Empagliflozin, film-tablet, 25mg once daily

Placebo, once daily

Outcomes

Primary Outcome Measures

Change in liver fat content
Change in liver fat content between baseline and 24 weeks measured with magnetic resonance spectroscopy

Secondary Outcome Measures

Full Information

First Posted
December 16, 2015
Last Updated
June 2, 2023
Sponsor
The Deutsche Diabetes Forschungsgesellschaft e.V.
Collaborators
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT02637973
Brief Title
Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes
Acronym
EmLiFa
Official Title
Effects of Empagliflozin on Liver Fat Content, Energy Metabolism and Body Composition in Patients With Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
August 2018 (Actual)
Study Completion Date
August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Deutsche Diabetes Forschungsgesellschaft e.V.
Collaborators
Boehringer Ingelheim

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Non-alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Experimental
Arm Description
Empagliflozin, film-tablet, 25mg once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, once daily
Intervention Type
Drug
Intervention Name(s)
Empagliflozin
Other Intervention Name(s)
Jardiance
Intervention Description
25 mg once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
No Drug Therapy
Intervention Description
once daily
Primary Outcome Measure Information:
Title
Change in liver fat content
Description
Change in liver fat content between baseline and 24 weeks measured with magnetic resonance spectroscopy
Time Frame
from baseline to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Roden, MD
Organizational Affiliation
Deutsches Diabetes Zentrum
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charite Universitaetsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
German Diabetes Center
City
Dusseldorf
Country
Germany
Facility Name
University Clinic Heidelberg
City
Heidelberg
Country
Germany
Facility Name
University Clinic Tübingen
City
Tübingen
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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