Diabetes Mellitus type 2
Conditions
Interventions
Trade Name: jardiance
Product Name: Empagliflozine
Product Code: A10BK03
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the p
Sponsors
Amsterdam University Medical Center - location VU Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Caucasian* • Both genders (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L) • Age: 45 - 80 years • BMI: >25 kg/m2 • For with people with diabetes - a diagnosis of T2DM with glycosylated haemoglobin (HbA1c) =6.5% (=48 mmol/mol) and 75 mL/min/1.73m2 at the Screening Visit (Visit 1). • In the normoglycemic, hypertensive, individuals: HbA1c 75 ml/min/1.73m2 should be treated with a stable dose of metformin and/or SU, people with an eGFR between =25 and =50 mL/min/1.73m2 should be treated with a stable dose of metformin, SU and/or insulin therapy for at least 3 months prior to inclusion • Patient specific antihypertensive dose of an angiotensin receptor blocker (ARB) (as per Investigator’s judgement) for at least 4 weeks prior to Visit 2 (Day 3). • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: History of unstable or rapidly progressing renal disease • Diagnosis of polycystic kidney disease. • Post renal transplant • History of or current lupus nephritis. • Abnormal vital signs, after 10 minutes supine rest, definas as any of the following (Visit 1): o Systolic blood pressure above 180 mmHg o Diastolic blood pressure above 110 mmHg • Current/chronic use of the following medication: SGLT2 inhibitors,TZD, GLP-1RA, DPP-4 inhibitors, , antimicrobial agents or chemotherapeutics. • Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status. • Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drug can be taken within a time-frame of 2 weeks prior to renal-testing • History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to the Screening visit. • Current urinary tract infection and active nephritis • Recent (3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN • History of or actual malignancy (except basal cell carcinoma) • History of or actual severe mental disease • Substance abuse (alcohol: defined as >4 units/day) • Allergy to any of the agents used in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Investigate the effects of 7 days of therapy with the SGLT2 inhibitor empagliflozin (10 mg QD) versus placebo on measured glomerular filtration rate (mGFR)) in metformin and/or sulfonyl (SU) treated T2DM patients with normal kidney function, metformin, SU and/or insulin-treated T2DM patients with impaired kidney function and hypertensive people without T2DM with impaired kidney function, all treated with RAS blockers.;Secondary Objective: To assess the effects of 7 days treatment with SGLT2 inhibitor empagliflozin (10 mg QD) versus placebo in metformin and/or SU-treated T2DM patients with normal kidney function, metformin, SU and/or insulin-treated T2DM patients with impaired kidney function and hypertensive people without T2DM with impaired kidney function on: 1) Renal hemodynamics including effective renal plasma flow (ERPF) and renal vascular resistance (RVR) 2) Systemic hemodynamics (mean arterial pressure (MAP) & heart rate) 3) Caffeine-induced changes in renal hemodynamics including GFR, ERPF and RVR 4) Empagliflozin-induced proximal sodium excretion by using fractional excretion of lithium as a surrogate of proximal sodium handling.;Primary end point(s): Investigate the effects of 7 days of therapy with the SGLT2 inhibitor empagliflozin (10 mg QD) versus placebo on measured glomerular filtration rate (mGFR)) in metformin and/or sulfonyl (SU) treated T2DM patients with normal kidney function, metformin, SU and/or insulin-treated T2DM patients with impaired kidney function and hypertensive people without T2DM with impaired kidney function, all treated with RAS blockers.;Timepoint(s) of evaluation of this end point: after 7 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To investigate the effects of 7 days of therapy with SGLT-2 inhibitor empagliflozin (10 mg QD) versus placebo on: • Other renal hemodynamics: o Effective Renal Plasma Flow (ERPF) o Renal Vascular Resistance (RVR) • Systemic hemodynamics, measured as: o Mean Arterial Pressure (MAP) • Caffeine-induced changes in renal and systemic hemodynamics: GFR, ERPF, RVR and MAP • Empagliflozin-induced proximal sodium excretion. o Fractional excretion of lithium will be used as a surrogate to measure proximal tubular sodium handling, wheres fractional excretion of sodium assesses total overall (proximal and distal (tubular sodium handling).;Timepoint(s) of evaluation of this end point: 7 days | — |
Countries
Netherlands
Contacts
Public ContactDaniel van Raalte
Amsterdam University Medical Center - location VU Medical Center
Outcome results
None listed