Role of Finerenone in African American Veterans With Diabetic Kidney Disease

NCT ID: NCT07155694

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2027-08-31

Brief Summary

Primary Objectives: To study podocyte specific injury markers (podocyte specific proteins, PSP) nephrin, podocalyxin and Wilms'Tumor (WT-1) protein in exosomes urine from African American Veterans with albuminuric stage 2 and 3 chronic diabetic kidney disease (DKD), using Empagliflozin or Finerenone or combination therapy.

Secondary Objectives: (1). Correlate changes in exosome-based PSP with standardized biomarkers of kidney injury including urine albumin/creatinine ratio (ACR) and estimated GFR. (2) with systemic inflammatory markers (focusing on vascular and endothelial function) that are already established such as interleukins (IL1, IL6, IL-12), hs-CRP and (3) arterial stiffness measures and with (4) APOL1 mRNA expression levels in peripheral blood derived mononuclear cells (MNC).

Detailed Description

Chronic kidney disease (CKD) is a complex medical condition imposing deleterious effects on multiple organ systems. Prevention of increased cardiovascular mortality and progression to end-stage kidney disease (ESKD) are two major unmet medical needs in patients with CKD, with or without diabetes mellitus, especially in those with albuminuria. In patients with Diabetic Kidney Disease (DKD), the cornerstone of management includes blood pressure control, proteinuria management, maintenance of normal body weight, dietary adherence, and avoidance of nephrotoxic drugs. The management of DKD has undergone extensive changes with the advent of several foundational classes of guideline-based medical therapies (GDMT) for DKD. These include SGLT2i, GLP1-RAs along with Renin-Angiotensin System-inhibitors (RASi). While the benefits of the SGLT2i class of diabetes medications such as Empagliflozin for cardio-kidney outcomes in CKD are well recognized from the landmark EMPA-REG trial, there is less understood in terms of mechanisms of benefit, especially in high-risk patient phenotypes for progression to kidney failure, such as APOL1 positive gene mutation. The results from the recent FIDELIO-DKD and FIGARO-DKD studies showed that finerenone (an aldosterone receptor inhibitor) resulted in a decreased risk of cardiovascular events and slows down CKD progression in patients with type 2 diabetes (T2DM). This was a significant breakthrough and adds an additional class of medication for the treatment of DKD. However, the generalizability of the findings was limited as only 4.7% of the patients were African-American.

The Veterans Health Administration is the largest integrated healthcare system in the USA providing a comprehensive database of patients with CKD. The Nephrology and Endocrinology divisions at DC VAMC manage 175 new CKD patients each month (of whom 70% have diabetes) and 95% are African Americans. African Americans suffer from CKD at significantly higher rates and account for more than 35% of all patients receiving dialysis in the United States. Aggressive management with newer T2DM meds with reno-protective effects is important to be started early. Recently identified genetic variants in the APOL1 gene, found mostly in African Americans may explain a significant proportion of the rising burden of albuminuric CKD in African Americans. APOL1 risk variants G1 and G2 are trypanolytic factors that protect against trypanosomiasis in continental Africa but are associated with a significantly higher risk for the development of podocytopathy and ultimately progressive CKD. Though CKD is quite prevalent in African American patients, the precise mechanism of APOL1 risk variants leading to the progression of DKD in this patient population is unknown and requires further investigation. Interestingly the studies on APOL1 nephropathy have established an association with podocytopathy. Abnormalities in podocyte biology play a central role in the pathogenesis of albuminuric CKD. In CKD with albuminuria, podocyte injury is a key component in the pathophysiology of albuminuric CKD, which is also accompanied by systemic inflammation. The degree of podocyte injury is currently best assessed by kidney biopsy, which is an invasive procedure and not performed in the vast majority of patients with CKD. Therefore, the patterns and extent of podocyte injury in albuminuric CKD is less well understood. The investigators and others have shown improved endothelial function and decreased podocyte-specific urine protein injury markers production with SGLT2i in DKD. Additionally, the literature suggests close crosstalk between the glomerular vascular endothelium and the podocyte. The effect of Finerenone and SGLT2i on markers of podocyte injury, as well as markers of endothelial dysfunction (injury/inflammation) deserve further elucidation, either each medication on its own or in combination in African Americans with proteinuria.

The comparator in this study is Empagliflozin which is a standard of care in DKD. However, the investigators hypothesize that the combination will be more efficacious that either medication alone and synergistic for podocytopathy and proteinuria reversal similar to CONFIDENCE trial even in a CKD prone population of African Americans with diabetes

Conditions

Diabetic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Finerenone

Finerenone 10mg orally daily for 4 months

Group Type: ACTIVE_COMPARATOR

Finerenone 10 MG

Intervention Type: DRUG

Take Finerenone 10 mg orally daily

Empagliflozin

Empagliflozin 10mg orally daily for 4 months

Group Type: ACTIVE_COMPARATOR

Empagliflozin 10 MG

Intervention Type: DRUG

Take Empagliflozin 10 mg orally daily for 4 months

Finerenone and Empagliflozin combination

Take 10mg Empagliflozin daily, followed by Fineronone 10mg daily after 4 weeks or 1 month of taking empagliflozin. The combination will continue for 3 months or 12 weeks

Group Type: ACTIVE_COMPARATOR

Finerenone 10 MG

Intervention Type: DRUG

Take Finerenone 10 mg orally daily

Empagliflozin 10 MG

Intervention Type: DRUG

Take Empagliflozin 10 mg orally daily for 4 months

Interventions

Finerenone 10 MG

Take Finerenone 10 mg orally daily

Intervention Type: DRUG

Empagliflozin 10 MG

Take Empagliflozin 10 mg orally daily for 4 months

Intervention Type: DRUG

Other Intervention Names

Kerendia; Jardiance

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of type 2 diabetes (HbA1C at or above 6.5%, or fasting blood glucose of more than 125 or random/ post prandial blood glucose of more than 199mg%)

2. African American veterans

3. Age 20-90 years

4. eGFR ≥25-89 mL/min/1.73 m2 by the CKD-EPI equation)

5. Albuminuria of 30 mg/g or higher

6. BMI=18-39.9

7. Blood pressure controlled to ≤140/90

8. Ability to provide informed consent before any trial related activities are conducted.

Exclusion Criteria

1. If a patient is on statin, need to be on a stable dose for a month.

2. Biopsy proven diagnosis of glomerular disease/glomerulonephritis

3. Active smokers,

4. Active skin wounds undergoing treatment or recent surgery within 1 month (due to possible aberrations in glycemic control)

5. Women who are pregnant, planning to become pregnant, nursing mothers, women of childbearing potential not using birth control measure

6. Hypersensitivity to empagliflozin or finerenone

7. Patients on dialysis

8. eGFR less than 25 mL/min/1.73 m2 by the CKD-EPI equation

9. Planned surgery or planned hospital admission within 5 months of participation in the study

10. At the discretion of PI to ensure health, safety, and well-being of the veteran, participation in this study may be stopped (please see withdrawal criteria)

11. Patients with prior history of diagnosis of heart failure with documented EF of less than 50.

12. Proven diagnosis of Polycystic Kidney Disease.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Sabyasachi Sen, MD, PhD

Chief of Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sabyasachi Sen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington DC VA Medical Center

Locations

Washington DC Veterans Affairs Medical Center (688)

Washington D.C., District of Columbia, United States

Countries

United States

Central Contacts

Sabyasachi Sen, MD, PhD

Role: CONTACT

sabyasachi.sen@va.gov

202-745-8000 ext. 55810

Shannen Nicole D Ubalde, MS

Role: CONTACT

shannen.ubalde@va.gov

202-745-8000 ext. 55835

Facility Contacts

Sabyasachi Sen, MD

Role: primary

sabyasachi.sen@va.gov

202-745-8303

Ping Li, MD

Role: backup

ping.li2@va.gov

202-745-8000 ext. 55910

Other Identifiers

1780095

Identifier Type: -

Identifier Source: org_study_id