ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 187 for:    BI10773

Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Type 2 Diabetics (EmDia)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02932436
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : August 15, 2018
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Philipp Wild, MD, MSc, Johannes Gutenberg University Mainz

Brief Summary:
The purpose of the EmDia trial is to compare the effects of empagliflozin with placebo in addition to standard diabetic treatment or dietetic treatment on cardiac diastolic function in patients with type 2 Diabetes mellitus.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Diastolic Dysfunction Drug: Empagliflozin Drug: Placebo Phase 4

Detailed Description:

Diabetes is a serious and increasing global health burden. It has been shown, that diabetes is associated with a two-fold higher risk for coronary heart disease, stroke and for the aggregate of other vascular death independently of other conventional risk factors. It is the leading cause of cardiovascular disease.

Diabetes mellitus substantially increases the risk of macrovascular and microvascular complications, such as vascular dysfunction with developing coronary, cerebrovascular, and peripheral arterial disease, heart failure, nerve disorders (neuropathy), eye complications (e.g. cataracts, glaucoma diabetic retinopathy), kidney disease (nephropathy), foot ulcers, restriction of mental function, and psychosomatic diseases (e.g. stress, anxiety and depression).

The most common of the cardiovascular complications in diabetics are ischemic cardiomyopathy and left ventricular (LV) dysfunction. Of particular interest here is the diastolic dysfunction, as an early sign of diabetic heart muscle disease followed by systolic damage.

Although diabetes has a decisive role in the development of cardiovascular disease, traditional glucose lowering agents have failed to convincingly show that intensive glucose control significantly reduces CVD events.

A new approach for treatment of adult patients with type 2 diabetes was found with the selective inhibition of sodium glucose cotransporter 2 (SGLT2). Studies have shown that empagliflozin, a potent SGLT2 inhibitor, not only effectively reduces the rates of hyperglycemia but also blood pressure and weight. (16, 18) In addition, beneficial effects on arterial stiffness and vascular resistance, visceral adiposity, albuminuria and plasma urate have been reported.

The results of the EMPA-REG OUTCOME study suggest that empagliflozin added to the standard therapy has a positive influence on cardiovascular outcomes and heart failure hospitalization in individuals with diabetic mellitus.

The aim of the present study is to investigate the effects of empagliflozin, in comparison with placebo, on cardiac and vascular function as well as on cardiac biomarker in individuals with type 2 diabetes with standard therapy, increased E/E' ratio and poor glycemic control.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 158 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IV, Single-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study on the Effects of Empagliflozin on Left Ventricular Diastolic Function Compared to Usual Care in Individuals With Type 2 Diabetes
Actual Study Start Date : October 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Empagliflozin
10 mg Empagliflozin daily per os for 12 weeks
Drug: Empagliflozin
10 mg per os daily for 12 weeks
Other Name: Jardiance

Experimental: Placebo
amount of Placebo corresponding to empagliflozin 10 mg daily per os for 12 weeks
Drug: Placebo
amount of Placebo corresponding to empagliflozin 10 mg per os daily for 12 weeks




Primary Outcome Measures :
  1. difference in E/E' ratio between 12 weeks after baseline and at baseline [ Time Frame: 12 weeks ]
    difference in E/E' ratio (noninvasive surrogate marker for left ventricular diastolic function (LVEDP) measured by 2D-echocardiography) between 12 weeks after baseline and at baseline


Secondary Outcome Measures :
  1. difference in E/E' ratio (change from baseline (V1) to 1 week follow-up) [ Time Frame: 1 week ]
    difference in E/E' ratio (change from baseline (V1) to 1 week follow-up (2D-echocardiography)

  2. difference in Left ventricular systolic function (LVEF) [ Time Frame: 1 week ]
    difference in Left ventricular systolic function (LVEF) from baseline to week 1

  3. difference in Left ventricular systolic function (LVEF) [ Time Frame: 12 weeks ]
    difference in Left ventricular systolic function (LVEF) from baseline to week 12

  4. difference in Left end-diastolic volume (LEDV) [ Time Frame: 1 week ]
    difference in Left end-diastolic volume (LEDV) from baseline to week 1

  5. difference in Left end-diastolic volume (LEDV) [ Time Frame: 12 weeks ]
    difference in Left end-diastolic volume (LEDV) from baseline to week 12

  6. difference in Carotid-femoral pulse wave velocity [ Time Frame: 1 week ]
    difference in Carotid-femoral pulse wave velocity (cf-PWV, vascular explorer - calculated) from baseline to week 1

  7. difference in Carotid-femoral pulse wave velocity [ Time Frame: 12 weeks ]
    difference in Carotid-femoral pulse wave velocity (cf-PWV, vascular explorer - calculated) from baseline to week 12

  8. difference in Augmentation index (AIx) [ Time Frame: 1 week ]
    difference in Augmentation index (AIx, vascular explorer) from baseline to week 1

  9. difference in Augmentation index (AIx) [ Time Frame: 12 week ]
    difference in Augmentation index (AIx, vascular explorer) from baseline to week 12

  10. difference in Arterial stiffness index (SI) [ Time Frame: 1 week ]
    difference in Arterial stiffness index (SI, photo plethysmography) from baseline to week 1

  11. difference in Arterial stiffness index (SI) [ Time Frame: 12 weeks ]
    difference in Arterial stiffness index (SI, photo plethysmography) from baseline to week 12

  12. difference in Reflection index [ Time Frame: 1 week ]
    difference in Reflection index (photo plethysmography) from baseline to week 1

  13. difference in Reflection index [ Time Frame: 12 weeks ]
    difference in Reflection index (photo plethysmography) from baseline to week 12

  14. difference in Brain natriuretic peptide (BNP) [ Time Frame: 1 week ]
    difference in Brain natriuretic peptide (BNP) from baseline to week 1

  15. difference in Brain natriuretic peptide (BNP) [ Time Frame: 12 weeks ]
    difference in Brain natriuretic peptide (BNP) from baseline to week 12

  16. difference in High sensitive troponin I (hs TnI) [ Time Frame: 1 week ]
    difference in High sensitive troponin I (hs TnI) from baseline to week 1

  17. difference in High sensitive troponin I (hs TnI) [ Time Frame: 12 weeks ]
    difference in High sensitive troponin I (hs TnI) from baseline to week 12

  18. difference in High sensitive C-reactive protein (hs CRP) [ Time Frame: 1 week ]
    difference in High sensitive C-reactive protein (hs CRP) from baseline to week 1

  19. difference in High sensitive C-reactive protein (hs CRP) [ Time Frame: 12 weeks ]
    difference in High sensitive C-reactive protein (hs CRP) from baseline to week 12

  20. difference in E/E' ratio (change from baseline (V1) to 12 weeks follow-up) in the subgroup of patients with eGFR 45-59 ml/min/1.73 m² [ Time Frame: 12 weeks ]
    difference in E/E' ratio (noninvasive surrogate marker for left ventricular diastolic function (LVEDP) measured by 2D-echocardiography) between 12 weeks after baseline and at baseline in the subgroup of patients with eGFR 45-59 ml/min/1.73 m²

  21. difference in E/E' ratio (change from baseline (V1) to 12 weeks follow-up) in the subgroup of patients with HbA1c 6.5%-6.9% [ Time Frame: 12 weeks ]
    difference in E/E' ratio (noninvasive surrogate marker for left ventricular diastolic function (LVEDP) measured by 2D-echocardiography) between 12 weeks after baseline and at baseline in the subgroup of patients with with HbA1c 6.5%-6.9%


Other Outcome Measures:
  1. difference in biomarkers of cardiac diseases [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in biomarkers of cardiac diseases

  2. difference in biomarkers of cardiac diseases [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in biomarkers of cardiac diseases

  3. difference in biomarkers of vascular diseases [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in biomarkers of vascular diseases

  4. difference in biomarkers of vascular diseases [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in biomarkers of vascular diseases

  5. difference in biomarkers of metabolic/diabetic status [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in biomarkers of metabolic/diabetic status

  6. difference in biomarkers of metabolic/diabetic status [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in biomarkers of metabolic/diabetic status

  7. changes in vascular/endothelial function [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in vascular/endothelial function

  8. changes in vascular/endothelial function [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in vascular/endothelial function

  9. changes in carotid atherosclerosis [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in carotid atherosclerosis

  10. changes in carotid atherosclerosis [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in carotid atherosclerosis

  11. changes in pulmonary function [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in pulmonary function

  12. changes in pulmonary function [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in pulmonary function

  13. changes in ophthalmological diseases [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in ophthalmological diseases

  14. changes in ophthalmological diseases [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in ophthalmological diseases

  15. changes in psychosomatic diseases [ Time Frame: 1 week ]
    changes between baseline and follow-up after 1 week in psychosomatic diseases

  16. changes in psychosomatic diseases [ Time Frame: 12 weeks ]
    changes between baseline and follow-up after 12 weeks in psychosomatic diseases

  17. association analysis for selected SNPs [ Time Frame: baseline ]
    association analysis for selected SNPs (measured at baseline)



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 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects meeting all of the following criteria at visit 0 (screening) will be considered for admission to the trial:

  • Diagnosis of type 2-diabetes mellitus with stable glucose-lowering background therapy and/or dietetic treatment for at least 12 weeks
  • In subjects without glucose-lowering background therapy: the application of Metformin was considered to be unsuitable due to drug intolerance
  • HbA1c level of ≥6.5% and ≤10.0% at visit 0 (screening) for subjects on antidiabetic background therapy or HbA1c level of ≥6.5% and ≤9.0% for drug-naïve subjects with dietetic treatment
  • Diastolic cardiac dysfunction E/E' ratio ≥8 (2D-echocardiography)
  • Age 18 - 84 years
  • BMI ≤ 45 kg/m² (Body Mass Index)
  • For women: post-menopausal for more than 12 months without an alternative medical cause can participate in the trial. Women with childbearing potential can only participate, if they are surgically sterile or a negative pregnancy test (serum or urine) is available at visit 1 and they are willing to practice highly effective birth control method during trial. Reliable highly effective contraception comprises

    • combined (estrogen and progesteron containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
    • progesteron-only hormonal contraception associated with inhibition of ovaluation (oral, injectable, implantable)
    • intrauterine device (IUD)
    • intrauterine hormone-releasing system (IUS)
    • bilateral tubal occlusion
    • vasectomised partner (provided that partner is the sole sexual partner and that the vasectomised partner has received medical assessment of the surgical success)
    • sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
  • Ability of subject to understand nature, importance and individual consequences of clinical trial
  • Signed and dated informed consent of the subject must be available before start of any specific trial procedures which is consistent with ICH-GCP guidelines and local legislation

Exclusion Criteria:

Subjects presenting with any of the following criteria at visit 0 (screening) will not be included in the trial:

  • Pretreatment with empagliflozin or other SGLT2 inhibitor within the last 3 months
  • Pretreatment with known inducers of UGT enzymes
  • Uncontrolled hyperglycemia with a glucose level > 240 mg/dl (>13.3 mmol/L) after an overnight fast
  • Impaired renal function, defined as eGFR <45 ml/min/1.73 m² of body-surface-area
  • End-stage renal failure or dialysis
  • Severe hepatic dysfunction, defined by serum levels of either SGPT, SGOT, or alkaline phosphatase above 3 x upper limit of normal (ULN)
  • Acute urinary tract infection (UTI)
  • Known acute genital infection (GI)
  • Symptomatic hypotension
  • Hematocrit above the upper limit of the reference range
  • Hypoglycemic tendencies
  • Severe PAD (Fontaine classification Stage IIb - IV)
  • Medical history of cancer and/or treatment for cancer within the last 5 years, subjects basalioma can be included in the study
  • Medical history of pancreatitis or surgery on pancreas
  • Known ketoacidosis (in the past)
  • Acute febrile disease
  • NYHA classification III - IV
  • Pregnant and/or nursing women at visit 1 (baseline)
  • Acute coronary syndrome, stroke or TIA within the last 2 months
  • Planned cardiac surgery or angioplasty within 3 months
  • Gastrointestinal surgeries that induce chronic malabsorption
  • Blood dyscrasia or any disorders causing hemolysis or unstable Red Blood Cells (e.g. malaria, babesiosis, hemolytic anemia)
  • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
  • Alcohol or drug abuse within the last 3 months that would interfere with trial participation
  • Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial (at visit 0 (screening) or at visit 1 (baseline))
  • Medical condition that does not allow enrollment in the trial at visit 1 (baseline)
  • Current treatment with systemic steroids or change in dosage of thyroid hormones within the last 6 weeks or any other uncontrolled endocrine disorder except type 2 diabetes mellitus
  • Hereditary glucose intolerance, galactose intolerance, Lapp-lactase deficiency or glucose-galactose-malabsorption
  • Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial (involving an investigational drug and/or follow-up)

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): NCT02932436


Contacts
Contact: Philipp Wild, MD, MSc 00496131 ext 17 170 philipp.wild@unimedizin-mainz.de
Contact: Claus Jünger, MD, M.san. 00496131 ext 17 170 claus.juenger@unimedizin-mainz.de

Locations
Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kardiologie, Präventive Kardiologie und Medizinische Prävention Recruiting
Mainz, Germany, 55131
Contact: Philipp Wild, MD    00496131 ext 17 170    philipp.wild@unimedizin-mainz.de   
Contact: Tommaso Gori, MD    00496131 ext 17 170    tommaso.gori@unimedizin-mainz.de   
Sponsors and Collaborators
Johannes Gutenberg University Mainz
Boehringer Ingelheim
Investigators
Principal Investigator: Philipp Wild, MD, MSc Johannes Gutenberg University Mainz

Responsible Party: Philipp Wild, MD, MSc, principal investigator, Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier: NCT02932436     History of Changes
Other Study ID Numbers: UMCM-2016EPI05
2016-001264-11 ( EudraCT Number )
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Philipp Wild, MD, MSc, Johannes Gutenberg University Mainz:
empagliflozin
diastolic function
poorly controlled type 2 diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs