SGLT2 Inhibition and Left Ventricular Mass

NCT02728453 | Terminated Phase 4

• 1 other identifier: CRC-KliPha-001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with type 2 diabetes mellitus are exposed to an excessive heart failure risk secondary to left ventricular hypertrophy and impaired diastolic filling, a condition not addressed by currently available treatments. The abnormality results from obesity-induced volume overload, increased blood pressure, and myocardial fat accumulation. By improving metabolism, body weight, and blood pressure, Empagliflozin addresses the root causes of type 2 diabetes-associated myocardial disease. We will assess left ventricular mass, function, and lipid content in patients with type 2 diabetes mellitus using cardiac magnetic resonance imaging and spectroscopy as well as echocardiography before and after empagliflozin or glimepiride treatment. We expect to observe improvements in left ventricular mass, function, and fat content with empagliflozin. The results of the study will help to position empagliflozin as an antidiabetic agent with the added value of protecting the heart.

Conditions

Diabetes Mellitus Type 2

Outcome Measures

Primary Outcomes (1)

• change in left ventricular mass

  change in left ventricular mass determined by cardiac MRI as the difference between 24 weeks and baseline

  baseline and 24 weeks

Secondary Outcomes (12)

• change in left ventricular end-systolic volume

  baseline and 24 weeks

• change in left ventricular function

  baseline and 24 weeks

• change in intramyocardial lipid content

  baseline and 24 weeks

• change in diastolic function

  baseline and 24 weeks

• change in HbA1c

  baseline and 24 weeks

Other Outcomes (5)

• change in cardiac fibrosis

  baseline and 24 weeks

• change in global long strain

  baseline and 24 weeks

• number of participants with abnormal laboratory values in the blood

  baseline and 4, 8, 12, 16, 20, 24 weeks

Study Arms (2)

Empagliflozin

EXPERIMENTAL

25 mg/d empagliflozin + matching glimepiride placebo for 24 weeks.

Drug: Empagliflozin

Glimepiride

ACTIVE COMPARATOR

2 or 4 mg/d glimepiride+ matching empagliflozin placebo for 24 weeks.

Drug: Glimepiride

Interventions

Empagliflozin DRUG

Treatment with empagliflozin vs. glimepiride to understand whether empagliflozin may reduce left ventricular mass in patients with type 2 Diabetes mellitus.

Also known as: Jardiance

Empagliflozin

Glimepiride DRUG

Treatment with empagliflozin vs. glimepiride to understand whether empagliflozin may reduce left ventricular mass in patients with type 2 Diabetes mellitus.

Also known as: Amaryl

Glimepiride

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women and men ≥40 and \<80 years of age
• patients with type 2 diabetes mellitus on stable anti-diabetic treatment for the last 3 months; at screening the following treatment conditions are allowed:
• metformin + sulfonylurea with HbA1c ≥6.5% and ≤9.0%
• metformin monotherapy with HbA1c ≥7.5% and ≤ 9.0%
• metformin + dipeptidylpeptidase-IV inhibitor with ≥6.5% and ≤9.0%
• waist circumference ≥80 cm in women or ≥94 cm in men
• women without childbearing potential defined by:
• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy
• hysterectomy
• ≥ 50 years and in postmenopausal state \> 1 year
• \< 50 years and in postmenopausal state \> 1 year with serum follicle-stimulating Hormone (FSH) \> 40 IU/l and serum estrogen \< 30 ng/l or a negative estrogen test, both at screening
• women of childbearing potential with a negative serum pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of 4 days following the last administration of study medication:
• correct use of reliable contraception methods. The following are acceptable: hormonal contraceptives (combined oral contraceptives, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUD/IUS) or a double barrier method, e.g. condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository)
• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)
• sexual relationship only with female partners

You may not qualify if:

• diabetes mellitus type 1
• uncontrolled diabetes mellitus type 2 with fasting glucose \> 13.3 mmol/l confirmed on a second day
• previous treatment with insulin, glucagon-like peptide-1 analogues, or pioglitazone during the last year before screening
• previous treatment with empagliflozin
• acute illness at screening or randomization according to judgement by the investigator or patient
• known or suspected hypersensitivity to empagliflozin, glimepiride or any excipients; known or suspected hypersensitivity to sulfonylureas or sulfonamides
• history of multiple severe hypoglycemic episodes
• any condition prohibiting MRI studies (e.g. metal implants, claustrophobia, body weight too high) including any suspected reaction after contrast agent application
• patient actively attempted to lose weight or experienced unintentional clinically significant weight loss during the last 3 months
• bariatric surgery or other gastrointestinal surgery procedures that induce chronic malabsorption
• treatment with any weight loss drug in the preceding 6 months
• planned significant changes of pre-study physical activity level during study participation
• heart failure New York Heart Association (NYHA) III - IV
• patients with known severe cardiovascular disease (e.g. myocardial infarction, unstable angina, stable coronary artery disease, stroke or transient ischemic attack)
• calculated glomerular filtration rate (eGFR) \<60 ml/min/1,73 m2

Sponsors & Collaborators

• Hannover Medical School: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Hannover Medical School

Hanover, 30625, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jens Jordan, Prof. Dr.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: April 5, 2016
• Study Start: April 27, 2016
• Primary Completion: September 25, 2017
• Study Completion: September 27, 2017
• Last Updated: March 22, 2019

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)