Efficacy and Mechanisms of Dapagliflozin in Promoting Kidney Function and Cardiovascular Health in Kidney Transplant Recipients

Study Overview
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Brief Summary
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Long-term allograft function in kidney transplant recipients (KTRs) remain suboptimal, and graft failure causes significant morbidity and mortality, with cardiovascular disease being the leading cause of death in KTRs and the most common cause of death with a functioning graft. Sodium-glucose cotransporter 2 (SGLT2) inhibitors safely lower cardiovascular and kidney disease risk in the non-transplant population, yet data in KTRs are lacking. This clinical trial seeks to establish the efficacy and safety of dapagliflozin, a SGLT2 inhibitor, for improving cardiovascular and kidney graft function in adult KTRs with type 2 diabetes and post-transplant diabetes, and to leverage innovate translational methods to define the underlying mechanisms of action.

Official Title
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Efficacy and Mechanisms of Dapagliflozin in Promoting Kidney Function and Cardiovascular Health in Kidney Transplant Recipients

Conditions
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Kidney Transplant; Complications, Vascular Diseases, Diabetes

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Kidney transplant received 1 year prior to randomization estimated glomerular filtration rate 30-90 ml/min/1.73m2 Urine albumin to creatinine ratio (ACR) 30-5000 mg/g Pre-existing type 2 diabetes or post-transplant diabetes mellitus Blood pressure <130/80 mm Hg prior to randomization Able to provide informed consent Stable immunosuppression for at least 3 months prior to baseline consisting of tacrolimus, mycophenolate mofetil/mycophenolic acid and prednisone Stable anti-hypertensive regimen for at least 1month prior to baseline Stable diabetes management for at least 3 months prior to baseline Stable angiotensin converting enzyme inhibitor/angiotensin receptor blocker use for at least 3 months prior to baseline (if applicable) Glucagon-like peptide-1 receptor agonist (GLP-1RA) for at least 3 months prior to baseline (if applicable) Exclusion Criteria: Type 1 diabetes Anticipated life expectancy <1 year Uncontrolled hypertension Hemoglobin A1c >9% Body mass index >40 kg/m2 New York Heart Association Class 3 or 4 heart failure symptoms, an EF ≤30%, or hospitalization for heart failure in the past 3 months Pregnancy, plans to become pregnant, or breastfeeding Current use of sodium glucose cotransporter-2 (SGLT2) inhibitors Current urinary or urogenital infection Use of anticoagulants (contraindication to kidney biopsy) Magnetic resonance imaging (MRI) contraindications History of lower-limb amputation irrespective of etiology Known hypersensitivity to dapagliflozin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Participants will receive dapagliflozin 10mg daily | Drug: Dapagliflozin 10mg Tab<br>* Dapagliflozin 10mg orally daily<br>|
| Placebo Comparator: Placebo<br>Participants will receive one placebo tablet daily | Drug: Placebo<br>* Placebo one tablet orally daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albuminuria | Measured by urine albumin to creatinine ratio | Change from baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney fibrosis | Measured by Magnetic Resonance Imaging (MRI) | Change from baseline to 12 months | 
| Kidney oxygenation | Measured by MRI | Change from baseline to 12 months | 
| Arterial stiffness | Measured by aortic pulse wave velocity | Change from baseline to 12 months |