A single-center, prospective, placebo-controlled, double-blind, randomized, cross-over mechanistic intervention study to investigate the effect of empagliflozin on kidney function in people with either preserved or impaired kidney function with or without type 2 diabetes

Phase 4

Withdrawn

• Conditions: adult-onset diabetes; Type 2 Diabetes Mellitus; 10018424; 10029149

• Registration Number: NL-OMON49123
• Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 72

Inclusion Criteria

* 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 <10.5% (<91 mmol/mol); and eGFR
(CKD-EPI) between *25 and *50 mL/min/1.73m2 or >75 mL/min/1.73m2 at the
Screening Visit (Visit 1).
* In the normoglycemic, hypertensive, individuals: HbA1c <6.5% (<48 mmol/mol)
and an eGFR (CKD-EPI) between *25 and *50 mL/min/1.73m2 at the Screening Visit
(Visit 1).
* In the diabetic arm: people with an eGFR >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

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 (<3 months) history of cardiovascular disease, including:
o Acute coronary syndrome
o Chronic heart failure (New York Heart Association grade II-IV)
o Stroke or transient ischemic neurologic disorder
* Complaints compatible with neurogenic bladder and/or incomplete bladder
emptying (as determined by ultrasonic bladder scan)
* Severe hepatic insufficiency and/or significant abnormal liver function
defined as aspartate aminotransferase (AST) >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Investigate the effects of 7 days of therapy with the SGLT2 inhibitor<br /><br>empagliflozin (10 mg QD) versus placebo on measured glomerular filtration rate<br /><br>(mGFR)) in metformin and/or sulfonyl (SU) treated T2DM patients with normal<br /><br>kidney function, metformin, SU and/or insulin-treated T2DM patients with<br /><br>impaired kidney function and hypertensive people without T2DM with impaired<br /><br>kidney function, all treated with RAS blockers.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To assess the effects of 7 days treatment with SGLT2 inhibitor empagliflozin<br /><br>(10 mg QD) versus placebo in metformin and/or SU-treated T2DM patients with<br /><br>normal kidney function, metformin, SU and/or insulin-treated T2DM patients with<br /><br>impaired kidney function and hypertensive people without T2DM with impaired<br /><br>kidney function on:<br /><br>1) Renal hemodynamics including effective renal plasma flow (ERPF) and renal<br /><br>vascular resistance (RVR)<br /><br>2) Systemic hemodynamics (mean arterial pressure (MAP) & heart rate)<br /><br>3) Caffeine-induced changes in renal hemodynamics including GFR, ERPF and RVR<br /><br>4) Empagliflozin-induced proximal sodium excretion by using fractional<br /><br>excretion of lithium as a surrogate of proximal sodium handling. </p><br>