Empagliflozin as a Modulator of Systemic Vascular Resistance and Cardiac Output in Patients With Type 2 Diabetes

NCT03132181 | Completed Phase 2

• 1 other identifier: 15-124
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

SGLT2 inhibitors are a novel class of glucose lowering drugs that act in the kidney by inhibiting SGLT2-mediated glucose reabsorption in the proximal tubule. The resulting increase in urinary glucose excretion leads to a reduction in plasma glucose levels. This is accompanied by reduction of total body weight due to urinary energy loss. In addition, glucose dependent osmotic diuresis contributes to blood pressure lowering effects of SGLT2 inhibition. Aim of the trial is to assess hemodynamic changes by empagliflozin, identify new empagliflozin dependent metabolic regulators and evaluate empagliflozin dependent effects on cardiac function.

Conditions

Diabetes Mellitus Type 2 (T2DM)

Keywords

Empagliflozin; Diabetes; Systemic vascular resistance; Cardiac output; Blood pressure

Outcome Measures

Primary Outcomes (2)

• Mode of action

  vascular resistance (dyn\*s/cm\^5)

  3 months

• Mode of action

  cardiac output (l/min)

  3 months

Secondary Outcomes (12)

• Hemodynamics

  3 months

• Hemodynamics

  3 months

• Energie expenditure

  3 months

• Cardio cascular

  3 months

• Urine

  3 months

Study Arms (2)

Empagliofizin

EXPERIMENTAL

Patients will receive empagliflozin 10 mg qd for a period of 3 months.

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Patients of the placebo arm will receive placebo tablets qd for a period of 3 months.

Other: Placebo

Interventions

Empagliflozin DRUG

Patient will be treaded according to standard care but additionally take one tablet Empagliflozin per day

Also known as: Jardiance

Empagliofizin

Placebo OTHER

Patient will be treaded according to standard care but additionally take one tablet placebo per day

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• Serum levels of HbA1c ≥ 6.5 %, despite treatment with diet and glucose lowering agents, which should include metformin (unless intolerance or contraindication to metformin exists)
• Age ≥ 18 years
• Participants of child-bearing age should use adequate contraception
• Written informed consent prior to study participation

You may not qualify if:

• Type 1 diabetes
• Systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 90 mmHg
• Age ≥ 75 years
• Pregnancy or lactating females
• Urinary tract infections or significant formation of residual urine in medical history
• Renal impairment (GFR \< 30 ml/min/1.73 m2)
• Liver disease (serum levels of AST, ALT or AP more than three times the upper limit of normal)
• Uncontrolled thyroid disease
• Endocrinopathies like Graves' disease, acromegaly, Cushing's disease
• Hypertensive retinopathy or encephalopathy
• Acute coronary syndrome, stroke or transient ischemic attack in last 6 weeks prior to randomization
• The subject is mentally or legally incapacitated
• Patients with newly diagnosed diabetes, who have not been subjected to diet and glucose lowering drug treatment.
• Patients with particular risk for ketoacidosis (alcohol abuse, pancreatitis, pancreatic insulin deficiency from any cause, caloric restriction etc.) or ketoacidosis in the past
• Frequent hypoglycaemic events (in the opinion of the investigator)

Sponsors & Collaborators

• RWTH Aachen University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Department of Internal Medicine I RWTH Aachen University Hospital

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Related Publications (8)

• Cherney DZ, Perkins BA, Soleymanlou N, Har R, Fagan N, Johansen OE, Woerle HJ, von Eynatten M, Broedl UC. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol. 2014 Jan 29;13:28. doi: 10.1186/1475-2840-13-28.

  PMID: 24475922 BACKGROUND

• Chilton R, Tikkanen I, Cannon CP, Crowe S, Woerle HJ, Broedl UC, Johansen OE. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015 Dec;17(12):1180-93. doi: 10.1111/dom.12572. Epub 2015 Oct 9.

  PMID: 26343814 BACKGROUND

• DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.

  PMID: 23735727 BACKGROUND

• Mauricio D. [Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus]. Med Clin (Barc). 2013 Sep;141 Suppl 2:31-5. doi: 10.1016/S0025-7753(13)70061-7. Spanish.

  PMID: 24444522 BACKGROUND

• Sha S, Polidori D, Heise T, Natarajan J, Farrell K, Wang SS, Sica D, Rothenberg P, Plum-Morschel L. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2014 Nov;16(11):1087-95. doi: 10.1111/dom.12322. Epub 2014 Jul 8.

  PMID: 24939043 BACKGROUND

• Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013 Aug 20;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.

  PMID: 24026259 BACKGROUND

• Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.

  PMID: 27299675 BACKGROUND

• Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. No abstract available.

  PMID: 26981940 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Nikolaus Marx, Univ.-Prof. Dr. med.

  University Hospital, Aachen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: April 27, 2017
• Study Start: April 24, 2017
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: February 12, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)