Vascular Effects of SGLT2i in Non-diabetic CKD

NCT07060417 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NEPH-006-24F
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-diabetic Chronic Kidney Disease

Keywords

CKD; SGLT2 inhibitor; endothelial function

Outcome Measures

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).

  baseline, 8 weeks, 16 weeks

Secondary Outcomes (4)

• Change in leg blood flow area-under-the-curve (LBF AUC) by Passive Leg Movement (PLM)

  baseline, 8 weeks, 16 weeks

• Changes in aortic stiffness as measured by carotid-femoral pulse wave velocity (PWV)

  baseline, 8 weeks, 16 weeks

• Changes in functional capacity as measured by handgrip exercise

  baseline, 8 weeks, 16 weeks

• Mobility

  baseline, 8 weeks, and 16 weeks

Other Outcomes (3)

• Changes in plasma biomarkers of systemic inflammation

  baseline, 8 weeks, 16 weeks

• biomarkers of oxidative stress

  baseline, 8 weeks, 16 weeks

• nitric oxide bioavailability

  baseline, 8 weeks, 16 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The placebo will be encapsulated to look identical to the study drug.

Drug: Placebo

Empagliflozin

OTHER

Matching 10-mg empagliflozin dose will be used.

Drug: Empagliflozin

Interventions

Empagliflozin DRUG

Empagliflozin 10 mg, encapsulated to match the placebo, will be used.

Also known as: Jardiance

Empagliflozin

Placebo DRUG

Matching placebo will be used.

Placebo

Eligibility Criteria

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

You may qualify if:

• adults aged 18 years of age or older
• eGFR 20-59 mL/min
• albuminuria \<300 mg/g

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

Location

MeSH Terms

Interventions

empagliflozin

Study Officials

• Monique Cho, MD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monique Cho, MD

CONTACT

(801) 582-1565; monique.cho@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization to either the placebo or empagliflozin group will be performed using a secure web-based system and allocation of empagliflozin vs. placebo in 1:1 ratio. The allocation of the study group will remain blinded to both participants and all study staff and investigators until the completion of the study. Participants will receive encapsulated empagliflozin and matching placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is 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.

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 11, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)