Diabetes, Kidney Transplant; Complications, Vascular Diseases
Conditions
Brief summary
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.
Interventions
DRUGDapagliflozin 10mg Tab
Dapagliflozin 10mg orally daily
DRUGPlacebo
Placebo one tablet orally daily
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Albuminuria | Change from baseline to 12 months | Measured by urine albumin to creatinine ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney oxygenation | Change from baseline to 12 months | Measured by MRI |
| Arterial stiffness | Change from baseline to 12 months | Measured by aortic pulse wave velocity |
| Left ventricular mass | Change from baseline to 12 months | measured by cardiac MRI |
| Kidney fibrosis | Change from baseline to 12 months | Measured by Magnetic Resonance Imaging (MRI) and kidney biopsy tissue |
| Kidney morphometry, metabolomics from paired kidney biopsies | Change from baseline to 12 months | measured by single cell RNA sequencing from paired kidney biopsies |
| safety and tolerability | baseline, 6 and 12 months | assessed on basis of adverse events |
| estimated glomerular filtration rate | Change from baseline to 12 months | estimated by CKD epi equation |
Countries
United States
Contacts
Primary ContactJessica Kendrick
Backup ContactPetter Bjornstad
Outcome results
None listed