Kidney Transplantation Recipients, Magnetic Resonance Imaging (MRI), Non-Diabetic Patients, Placebo Control Design, Randomized Controlled Trial, Sodium-Glucose Transporter 2 Inhibitors
Conditions
Keywords
SGLT2i, Kidney Transplant, Kidney Transplant Recipients, MRI, Magnetic resonance Imaging, BOLD-MRI, Blood oxygen level dependent MRI, non-diabetic patients, Sodium-glucose Transporter 2 inhibitors, RCT
Brief summary
The goal of this clinical trial is to investigate if a single dose of oral SGLT2i, (50 mg Jardiance) will change oxygen tension in the kidney transplant. The main questions it aims to answer are: * Does a single dose of oral SGLT2i (50 mg Jardiance) change oxygen tension in the kidney transplant cortex and medulla, estimated by magnetic resonance imaging? * Does a single dose of oral SGLT2i (50 mg Jardiance) change kidney transplant cortical and medullary perfusion? * Does a single dose of oral SGLT2i (50 mg Jardiance) change kidney transplant artery blood flow? * Does a single dose of oral SGLT2i (50 mg Jardiance) change blood glucoses, blood pressure and heart rate? Researchers will compare a single dose of oral SGLT2i (50 mg Jardiance) to a placebo (a look-alike substance that contains no drug) to see if a single dose of oral SGLT2i (50 mg Jardiance) changes oxygen tension in the kidney transplant. Kidney transplant recipients with out diabetes will: * Meet for two intervention days. * A single dose of oral SGLT2i (50 mg Jardiance) or placebo will be given in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment. * Kidney cortex oxygenation, and blood flow in different compartments of the kidney transplant, is estimated by blood-oxygen-dependent level magnetic resonance imaging (BOLD-MRI). Patients are evaluated by routine clinical examination and routine biochemical measures for kidney transplant patients.
Detailed description
Background: Kidney transplantation is the best treatment of end-stage renal disease (ESRD), although median allograft survival is only 15 years. In non-transplant diabetic and non-diabetic patient's sodium-glucose co-transporter type 2 inhibitors (SGLT2i) protect kidney function, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation and relieve hypoxia. Hypothesis: SGLT2i in kidney transplant recipients (KTR) will improve kidney allograft cortex oxygenation. Research Objective: We aim to test the acute effect of SGLT2i on kidney allograft oxygen tension. Design: A randomized, double-blind, placebo-controlled, crossover intervention study. Designed according to the CONSORT statement Methods: A single dose of oral SGLT2i (50 mg Jardiance) and placebo in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment. Kidney cortex oxygenation and blood flow in different compartments of the kidney allograft will be estimated by blood-oxygen-dependent level magnetic resonance imaging (BOLD-MRI). Patients will be evaluated by routine clinical examination and routine biochemical measures for transplant patients. Primary endpoint: \- Kidney allograft cortical and medullary oxygen tension, estimated by BOLD-MRI based renal T2\* relaxation rate. Secondary endpoint: * Renal cortical and medullary perfusion ml/100 g/min * Renal artery blood flow ml/min * Blood glucose mmol/L * Systolic blood pressure (SysBP) and diastolic blood pressure (DiaBP) mmHg * Heart rate (HR), beats min-1 Study population: 8 Non-diabetic kidney transplant recipients \> 6 months post-transplant and stable eGFR \>20 ml/min will be recruited from Odense University Hospital (OUH) kidney transplant outpatient clinic.
Interventions
DRUGJARDIANCE 25mg
The intervention will be SGLT2i compared with placebo. The trial include a total of 8 non-diabetic kidney transplant recipients. 4 patients will randomly be assigned to start in the active arm, and treated with a single dose SGLT2i at intervention day 1 and a single dose placebo at intervention day 2. 4 patients will randomly be assigned to start in the non-active arm, each participant will be treated with a single dose placebo at intervention day 1 and a single dose SGLT2i at intervention day 2.
DRUGPlacebo
The intervention will be SGLT2i compared with placebo. The trial include a total of 8 non-diabetic kidney transplant recipients. 4 patients will randomly be assigned to start in the active arm, and treated with a single dose SGLT2i at intervention day 1 and a single dose placebo at intervention day 2. 4 patients will randomly be assigned to start in the non-active arm, each participant will be treated with a single dose placebo at intervention day 1 and a single dose SGLT2i at intervention day 2.
Sponsors
Odense University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double blinded, placebo controlled, cross-over intervention study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, age ≥ 18 years. * Non-diabetic kidney transplant recipients * \> 6 months post-transplant * Stable eGFR\> 20 ml/min (defined as eGFR 20 ml/min ± 5 ml/min variation in the last 3 months) * Immunosuppressive: Tacrolimus (Adport) and Mycophenolatmofetil (Myfenax/Cellcept/Mycophenolatmofetil) * Capable of lying in a MR-scanner * Capable of providing a signed informed consent and comply with study requirements. * Negativ pregnancy test
Exclusion criteria
* Diabetic kidney disease type 1 or 2 (World Health Organization (WHO) criteria) * Hemoglobin A1c ≥ 48 mmol/mol * Fasting venous plasma glucose ≥ 7,0 mmol/l or * 2-hours venous plasma glucose ≥ 11,1 mmol/l after oral glucose tolerance test (OGTT). * Renal allograft failure (eGFR\< 20 ml/min) * Alanine aminotransferase (ALAT) \> 3 x upper normal limit * Bilirubin \> 2 x upper normal limit * Prednisone treatment * Pregnancy * Breastfeeding *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kidney allograft cortex oxygenation, T2* | T2* measured at baseline, 3 and 6 hours post-intervention | BOLD-MRI, T2\* cortex, s-1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal cortical perfusion, (ml/100g/min) | Renal cortical perfusion, measured at baseline, 3 and 6 hours post-intervention | BOLD-MRI estimated renal cortical perfusion, (ml/100 g/min) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Renal allograft artery blood flow (ml/min) | Renal allograft artery blood flow measured at baseline, 3 and 6 hours post-intervention | BOLD-MRI, renal allograft artery blood flow (ml/min) |
| Blood glucose (mmol/L) | Blood glucose, measured at baseline, 3 and 6 hours post-intervention | Blood glucose (mmol/L), estimated by handheld blood glucose meter |
| Blood pressure | Bloodpressure measured at baseline, 3 and 6 hours post-intervention | Systolic and diastolic blood pressure (mmHg), Estimated by a validated blood pressure device. |
Countries
Denmark
Outcome results
None listed