Ignite Creation Date:
2024-05-06 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 3:12 PM
Study NCT ID:
NCT06110130
Status:
RECRUITING
Last Update Posted:
2024-04-29
First Post:
2023-10-25
Brief Title:
Effect of Empagliflozin on Podocyte Specific Proteins in African American Veterans With NDKD
Sponsor:
Washington DC Veterans Affairs Medical Center
Organization:
Washington DC Veterans Affairs Medical Center
Study Overview
Official Title:
Effect of Empagliflozin on Podocyte Specific Proteins Injury Markers in African American Veterans With Albuminuric Non-Diabetic Chronic Kidney Disease
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NDKD
Brief Summary:
Primary ObjectiveTo study podocyte specific injury markers in African American Veterans with non-diabetic kidney diseaseNDKD on empagliflozin therapy
Primary Endpoint Assess the effect of Empagliflozin on podocyte-specific proteins in exosomes isolated from subjects urine such as nephrin podocalyxin and WilmsTumor WT-1 protein
Secondary Objective
1 Correlate changes in exosome-based podocyte specific proteins with standardized biomarkers of kidney injury including urine albumincreatinine ratio ACR and estimated GFR
2 Correlate systemic inflammatory markers focusing on vascular and endothelial function that are already established such as interleukins IL1 IL6 IL-12 hs-CRP and arterial stiffness measures with urine exosome-based podocyte protein estimation
3 Correlate urine podocyte-specific protein markers with APOL1 mRNA expression levels in blood mononuclear cells MNC
Primary Endpoint Assess the effect of Empagliflozin on podocyte-specific proteins in exosomes isolated from subjects urine such as nephrin podocalyxin and WilmsTumor WT-1 protein
Secondary Objective
1 Correlate changes in exosome-based podocyte specific proteins with standardized biomarkers of kidney injury including urine albumincreatinine ratio ACR and estimated GFR
2 Correlate systemic inflammatory markers focusing on vascular and endothelial function that are already established such as interleukins IL1 IL6 IL-12 hs-CRP and arterial stiffness measures with urine exosome-based podocyte protein estimation
3 Correlate urine podocyte-specific protein markers with APOL1 mRNA expression levels in blood mononuclear cells MNC
Detailed Description:
Nephropathy is a progressive complication of DKD and NDKD and substantially increases morbidity and mortality Clinicians frequently measure proteinuria using urine protein creatinine and urine albumincreatinine ratios which in several instances do not manifest substantial improvement even after an intervention such as SGLT2i particularly if the intervention period is is less than 6 months There is therefore a clear need for other markers of podocyte injury in early phases of chronic kidney disease
Based on published studies podocyte-specific injury proteins such as podocalyxin Nephrin and Wilms tumor 1 WT1 can be candidate marker proteins of injury Urinary exosome analysis is a non-invasive and potentially more sensitive assay These sensitive markers would reduce the need for biopsies to detect podocytopathy
The Veterans Health Administration has been a prominent caregiver to the African American community across the United States Over the past decade investigators have established the basic population genetics and epidemiology of APOL1-associated kidney disease and are making progress in understanding disease mechanisms at the cellular and molecular levels With therapeutic approaches for APOL1 kidney disease now being explored by many groups in pharma and academia studies to assess the relationship of APOL1 gene expression levels with podocyte injury in CKD are of paramount importance and will better inform treatment in the near future These studies may address one important cause of the significant racial disparity in CKD rates among African-Americans This study aim to explore mechanistic insights gained from the effect of SGLT2i on podocyte injury markers further in the backdrop of APOL1 expression to understand the potential therapeutic impact SGLT2i may have in this clinical context
As APOL-1 gene mutation is much more common in African Americans and approximately 80 of VA population is African Americans this study has been decided to enroll only from African American race in order to keep the population homogenous and achieve statistically significant results Though the study will only include African Americans the study will be quite relevant in USA as worsening CKD is a major health problem in this country and the African American patient population is at particularly at a high risk for progressive CKD A largely under-recognized public health issue CKD is the ninth leading cause of death in the US today Although African Americans constitute 13 of the population they suffer more than triple the rate of kidney failure of Caucasians
Based on published studies podocyte-specific injury proteins such as podocalyxin Nephrin and Wilms tumor 1 WT1 can be candidate marker proteins of injury Urinary exosome analysis is a non-invasive and potentially more sensitive assay These sensitive markers would reduce the need for biopsies to detect podocytopathy
The Veterans Health Administration has been a prominent caregiver to the African American community across the United States Over the past decade investigators have established the basic population genetics and epidemiology of APOL1-associated kidney disease and are making progress in understanding disease mechanisms at the cellular and molecular levels With therapeutic approaches for APOL1 kidney disease now being explored by many groups in pharma and academia studies to assess the relationship of APOL1 gene expression levels with podocyte injury in CKD are of paramount importance and will better inform treatment in the near future These studies may address one important cause of the significant racial disparity in CKD rates among African-Americans This study aim to explore mechanistic insights gained from the effect of SGLT2i on podocyte injury markers further in the backdrop of APOL1 expression to understand the potential therapeutic impact SGLT2i may have in this clinical context
As APOL-1 gene mutation is much more common in African Americans and approximately 80 of VA population is African Americans this study has been decided to enroll only from African American race in order to keep the population homogenous and achieve statistically significant results Though the study will only include African Americans the study will be quite relevant in USA as worsening CKD is a major health problem in this country and the African American patient population is at particularly at a high risk for progressive CKD A largely under-recognized public health issue CKD is the ninth leading cause of death in the US today Although African Americans constitute 13 of the population they suffer more than triple the rate of kidney failure of Caucasians
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None