Purpose

The purpose of the study is to determine the renal and cardiovascular protective effects of antidiabetic medications 1) Standard of care 2) Empagliflozin, 3) Semaglutide, or 4) Fenerenone 5) Empaglifozin + Fenerenone, over the course of 52 weeks.

Category

IRB Number
STUDY00001235
NCT Number
-
Sponsor
-



Study Contact

Deanna Juarez
210-450-9269
juarezd2@uthscsa.edu

Principal Investigator
Carolina Solis-Herrera

Francisca Acosta
210-562-4094
acostafm@uthscsa.edu

Deanna Juarez
210-450-9059
juarezd2@uthscsa.edu



Eligibility

Eligible Ages
18+
Eligible Genders
ALL
Accepts Healthy Volunteers
No

Inclusion Criteria

    1. Patients aged ≥18 years with KTR 
    1. ≥3 months and <24 months post kidney transplantation 
    1. Diagnosis of T2DM prior to KTX, HbA1c = 6.0-12.0% 
    1. Estimated glomerular filtration rate [eGFR] ≥20 ml/min/1.73m2 
    1. Urine albumin: creatine ratio (UACR) ≥30ug/mg 
    1. Patients with serum potassium ≤4.8 mEq/L at both the run-in visit and the screening visit. 
    1. Stable kidney allograft function (within 20% baseline eGFR) and based on the clinical judgement of the investigator. 
    1. Preserved kidney allograft function defined as an eGFR ≥25mL/min/1.73m2 with <20% variation in the eGFR in the last 30 days. 
    1. Body-mass index [BMI] between 18.5-40kg/m2 
    1. BP <160/100 and >90/60 at screening 
    1. Body weight much be stable (+/- 5 pounds) over the last 3 months. 
    1. Oral diuretics and anti-hypertensives, if prescribed to patient according to local guidelines and discretion of the investigator, should be stable for at least 1 wk prior to randomization  
    1. Stable anti-rejection therapy for the last 30 days.  
    1. All ethnic groups.  
    1. Willing to adhere to medication regimen for up to 52 wks.  
    1. Patient on an ACE or ARB follows: i. For ≥4 weeks prior to the run-in visit, treated with either an ACEi or an ARB or both ii. Starting with the run-in visit, treated with only an ACEi or ARB. iii. For ≥4 weeks prior to the screening visit, treated with the maximum tolerated labeled dose (but not below the minimal labeled dose) of only an ACEi or an ARB (not both) preferably without any adjustments to dose.  
    1. For women of child-bearing potential, a negative pregnancy test at screening visit and agreeing to use adequate contraception (≥2 effective methods of birth control, of which ≥1 is a physical barrier). Patient with ability to understand and follow study-related instructions.  
    1. Patient providing written informed consent before any study-specific criteria  

Exclusion Criteria

    1. Type 1 diabetes 
    1. History of multi-organ transplant 
    1. Patients on SGLT2i, GLP1RA, or Finerenone, 1 month prior to screening.  
    1. eGFR by CKD EPI <30ml/mi/1.73m2  
    1. Participation in the MRI Study is excluded for certain pacemakers, electronic implants, shrapnel of the eye and certain types of aneurysm clips. 
    1. Documented recurrent lupus nephritis, Antineutrophilic Cytoplasmic Antibody (ANCA) vasculitis, membranoproliferative glomerulonephritis (including C3 glomerulopathy) 
    1. History of solid organ transplantation other than kidney 
    1. UACR >3500 mg/g at screening. This may be reassessed if one of the three first morning urine samples is >3500 mg/g at the screening visit. 
    1. Acute kidney injury requiring dialysis within 6 months prior to screening. 
    1. Addison's disease. 
    1. Hepatic insufficiency classified as Child-Pugh C 
    1. Pregnancy, breast feeding or intention to become pregnant. 
    1. Concomitant therapy with spironolactone, eplerenone, or potassium-sparing diuretic which cannot be discontinued at least 4 weeks prior to screening. 
    1. SGLT2i is used at the time of enrollment. 
    1. Use of potent CYP3A4 inhibitors or inducers (to be stopped at least 7 days before randomization). 
    1. Known allergy/sensitivity to study drugs/ingredients.  
    1. Major oncologic diagnosis in the last 5 yrs.  
    1. Inability or unwillingness of individual or legal guardian/representative to give written informed consent. Diagnosis of type 1 diabetes.  
    1. Presence of acute coronary syndrome, stroke or transient ischemic attack in the 3 months prior to screening.  
    1. Prior episode of graft pyelonephritis in the 1 month prior to screening. Episode of acute graft rejection in the 3 months prior to screening.   
    1. Initiation of a new immunosuppressive agent or discontinuation of an immunosuppressive agent in the 1 month prior to screening.  
    1. Active untreated urinary or genital tract infection. 
    1. Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment 
    1. Severe hypoglycemia within 3 months of screening, or hypoglycemia unawareness.  
    1. Malignancy in the last 5 years. 
    1. Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome (e.g., immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome etc.). 



Study Design

Arm Groups