Vascular Effects of SGLT2i in Non-diabetic CKD
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Empagliflozin, Placebo.
- Who it may be relevant to
- Registry conditions: Non-diabetic Chronic Kidney Disease. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
The Effects of SGLT2 Inhibition on Vascular Health and Physical Function in Veterans With CKD
Overview
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.
Detailed description
Overall Strategy: The investigators propose a randomized, double-blind, placebo-controlled, phase-II study in 52 Veterans with non-diabetic CKD without heavy albuminuria (\<300 mg/g) and eGFR 20-59 mL/min/1.73m2 to investigate if empagliflozin, a selective SGLT2i, can improve vascular function, functional capacity, and plasma biomarkers of inflammation, oxidative stress, and nitric oxide (NO). Veterans will be recruited from the Salt Lake City VA and randomized to 10 mg of empagliflozin or placebo at 1:1 ratio and treated for 16 weeks.
Overarching Hypothesis: SGLT2 inhibition improves endothelial function in both macro- and micro-vasculature, in part, by mitigating inflammation and oxidative stress and augmenting NO bioavailability in patients with CKD, even in the absence of heavy albuminuria. The improved vascular function contributes to increased functional capacity.
Specific Aim 1: Comprehensively evaluate the efficacy of empagliflozin to improve vascular health, as determined by conduit artery endothelium-dependent vasodilation (flow-mediated dilation, FMD), peripheral microvasculature reactivity (passive limb movement, PLM), and arterial stiffness (carotid-femoral pulse wave velocity, PWV), in non-diabetic Veterans with CKD and albuminuria \<300 mg/g.
Specific Aim 2: Evaluate the efficacy of empagliflozin to improve functional capacity using (a) handgrip exercise and (b) mobility tests (Timed Up-and-Go test, gait speeds, and 6-minute walk).
Specific Aim 3 (Exploratory): Evaluate the efficacy of empagliflozin to (a) reduce plasma biomarkers of systemic inflammation (C-reactive protein, interleukin-6, tumor necrosis factor- ) and oxidative stress (free radical concentration assessed by electron paramagnetic resonance spectroscopy) and (b) increase plasma NO, as reflected by plasma nitrite and nitrosyl hemoglobin levels.
Interventions
- Drug Empagliflozin
Empagliflozin 10 mg, encapsulated to match the placebo, will be used. - Drug Placebo
Matching placebo will be used.
Primary outcome measures
- Change in endothelium-dependent vasodilation as measured by flow mediated dilation (FMD) [Time frame: baseline, 8 weeks, 16 weeks]
Secondary outcome measures (4)
- Change in leg blood flow area-under-the-curve (LBF AUC) by Passive Leg Movement (PLM) [Time frame: baseline, 8 weeks, 16 weeks]
- Changes in aortic stiffness as measured by carotid-femoral pulse wave velocity (PWV) [Time frame: baseline, 8 weeks, 16 weeks]
- Changes in functional capacity as measured by handgrip exercise [Time frame: baseline, 8 weeks, 16 weeks]
- Mobility [Time frame: baseline, 8 weeks, and 16 weeks]
Eligibility criteria
Inclusion criteria
- adults aged 18 years of age or older
- eGFR 20-59 mL/min
- albuminuria <300 mg/g
Exclusion criteria
- Type 1 or 2 diabetes mellitus
- expected to start dialysis or receive kidney transplantation or die within 4 months
- prior therapy with SGLT2i within the previous year
- unable to participate in the physical function tests (hand grip, walk)
- infections requiring intravenous antibiotic treatment
- malignancy requiring systemic therapy
- extremity skin ulceration requiring active therapy
- history of Fournier's gangrene
- severe hypoglycemia requiring external assistance within the past one year
- known allergy to empagliflozin
- pregnancy
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 1 center
- VA Salt Lake City Health Care System, Salt Lake City, UT — Salt Lake City
Identifiers
NCT: NCT07060417 · NEPH-006-24F