CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

Study Overview
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Brief Summary
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CREST-KT is a single-center, double-blinded, randomized trial of empagliflozin therapy in 72 kidney transplant recipients with (n=36) and without type 2 diabetes (n=36). After evenly dividing patients by type 2 diabetes diagnosis, patients will be randomized 2:1 to empagliflozin 10mg versus placebo.

Detailed Description
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A screening visit will occur at which time an informed consent will be obtained, and eligibility determined. Women of childbearing potential will have a serum pregnancy test performed. This will be followed by a baseline visit. A renal biopsy and a 3D echocardiogram will be performed. At the next visit randomization will be performed and the subjects will receive their study medication, either empagliflozin or a placebo. Following the randomization visit the subject will return every 3 months (visits 2-7) for a total of 6 visits spanning 18 months. At each visit vital signs and weight will be taken. Other procedures include labs drawn for hematology, basic chemistry, coagulation, Glycated hemoglobin and serum insulin. A 3 D echocardiogram is repeated on Visits 4 and 6. A renal biopsy is repeated on Visit 3.

Official Title
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CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

Conditions
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Kidney Transplant; Complications, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Empagliflozin10Mg Tab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Equal to or greater than 12 months and up tp 60 months post kidney transplant Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid Able to provide written consent - Exclusion Criteria: Type I diabetes Any other solid organ transplant Hemoglobin A1c greater than 12 % SGLT2i use at the time of enrollment Prior SGLT2i allergy or intolerance Pregnant or nursing at the time of enrollment History of antibody medicated rejection (AMR) or a Banff score greater than 2B for acute cellular rejection (ACR) Active anticoagulant use other than aspirin 81 mg for primary prevention of cardiovascular disease Known positive donor-specific antibodies prior to enrollment Uncircumcised men Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment Any genital infections over the 12 months prior to enrollment -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-controlled, double-blind, randomized clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I: With Type II Diabetes<br>Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo. | Drug: Empagliflozin10Mg Tab<br>* Empagliflozin10 Mg daily or placebo daily for 18 months<br>Drug: Placebo<br>* 10Mg Placebo Tab<br>|
| Active Comparator: Arm 2: Without Diabetes<br>Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo | Drug: Empagliflozin10Mg Tab<br>* Empagliflozin10 Mg daily or placebo daily for 18 months<br>Drug: Placebo<br>* 10Mg Placebo Tab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in kidney function as measured by eGFR | eGFR will be measured by blood test | Baseline, 6 months, 9 months, 12 months and 18 months | 
| Change in kidney function as measured by albuminuria | Albuminuria will be measured by urine Albumin/Creatinine Ratio | Baseline, 6 months, 9 months, 12 months and 18 months | 
| Change in cardiac structure | Cardiac structure as measured by the 3D echocardiogram | Baseline, month 9 and month15 | 
| Change in blood insulin level | Blood insulin level will be determined lab values | Baseline, month 6 and month 18 | 
| Change in fasting blood sugar | Fasting Blood sugar will be determined lab values | Baseline, month 6 and month 18 | 
| Number of Urinary Tract infections | Data to be gathered from chart review and patient report | up to 18 months | 
| Number of Genital infections | Data to be gathered from chart review and patient report | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in kidney biopsy as measured by percentage of interstitial fibrosis |  | Baseline and 6 months | 
| Changes in Hemoglobin A1C as measured by blood work |  | Baseline, Months 3,6,9,12,15 and 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post operative kidney transplant