Vascular Effects of SGLT2i in Non-diabetic CKD
ConditionNon-diabetic Chronic Kidney Disease
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVA Office of Research and Development
About this trial
Empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), is a novel diabetic medication that reduces the risk of progression of chronic kidney disease (CKD) and heart failure and improves exercise tolerance regardless of the diabetes status. One of the important ways that empagliflozin improves health may be through its benefits on blood vessels. The effects of empagliflozin on blood vessels and physical function have not been examined in patients with chronic kidney disease, and it is less clear if empagliflozin may be beneficial in patients with chronic kidney disease without heavy urinary protein leakage. The investigators will examine if empagliflozin can improve blood vessel function and exercise tolerance in Veterans with chronic kidney disease without heavy urinary protein leakage.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
eGFR (estimated glomerular filtration rate) 20-59 mL/min (milliliters per minute)
albuminuria <300 mg/g (milligrams per gram)
Disqualifiers
Type 1 or 2 diabetes mellitus
expected to start dialysis or receive kidney transplantation or die within 4 months
prior therapy with SGLT2i (Sodium-Glucose Co-Transporter 2 inhibitors) within the previous year
unable to participate in the physical function tests (hand grip, walk)
Trial design
Design model
Parallel
Treatments tested in this trial
Empagliflozin
DrugEmpagliflozin 10 mg, encapsulated to match the placebo, will be used.
Placebo
DrugMatching placebo will be used.
Treatment groups
52 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 1 intervention
Group B: EmpagliflozinOther 1 intervention
Trial outcomes
Primary outcomes
1
Change in endothelium-dependent vasodilation as measured by flow mediated dilation (FMD)
Brachial artery FMD will be used to assess if empagliflozin can improve endothelial function of conduit arteries in the upper limb. Brachial artery FMD outcome will be quantified as the maximal change in brachial artery diameter during the two-minute period after cuff release, expressed as a percentage increase from the pre-occlusion value (%FMD).
Time frame
baseline, 8 weeks, 16 weeksSecondary outcomes
1
Change in leg blood flow area-under-the-curve (LBF AUC) by Passive Leg Movement (PLM)
PLM measures the movement-induced increase of blood flow mediated mostly by nitric oxide in feed arteries and microvascular beds of the leg. The total hyperemic response to PLM, expressed as LBF AUC, will be used as the main PLM endpoint.
Time frame
baseline, 8 weeks, 16 weeks2
Changes in aortic stiffness as measured by carotid-femoral pulse wave velocity (PWV)
Carotid-femoral PWV is the gold standard for non-invasive assessment of central arterial stiffness, and our study will follow the established guidelines.
Time frame
baseline, 8 weeks, 16 weeks3
Changes in functional capacity as measured by handgrip exercise
Handgrip strength will be measured during the maximal voluntary contraction using a handgrip dynamometer. The highest value of three maximal contractions will be used.
Time frame
baseline, 8 weeks, 16 weeks4
Mobility
Timed Up-and-Go test will be used to assess sequential mobility tasks that incorporate walking and turning. The gait speed test over a 10-meter distance will be assessed during both comfortable and fast-gait speeds. The 6-minute walk test will measure the total distance covered during a 6-minute duration.
Time frame
baseline, 8 weeks, and 16 weeksOther outcomes
1
Changes in plasma biomarkers of systemic inflammation
Assays for plasma TNF-alpha (Tumor necrosis factor-alpha), CRP (C-reactive protein), IL-6 (Interleukin-6) will be performed using a quantitative multiplex bead assay.
Time frame
baseline, 8 weeks, 16 weeks2
biomarkers of oxidative stress
Plasma free radicals will be measured via electron paramagnetic resonance (EPR) spectroscopy.
Time frame
baseline, 8 weeks, 16 weeks3
nitric oxide (NO) bioavailability
Measures of NO bioavailability will be assessed using both nitrosyl-hemoglobin (NO-Hb) and ozone-chemiluminescence (Sievers Nitric Oxide Analyzer) methods for NO2-.
Time frame
baseline, 8 weeks, 16 weeksSponsors and contacts
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Source ClinicalTrials.gov
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