Clinical trial NCT06933355: Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension
Official title: Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension: A Randomized, Double-blind, Placebo Controlled Crossover Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Kidney Transplantation Recipients
Magnetic Resonance Imaging (MRI)
Sodium-Glucose Transporter 2 Inhibitors
Non-Diabetic Patients
Randomized Controlled Trial
Placebo Control Design
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
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2025-04-18
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, double blinded, placebo controlled, cross-over intervention study.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* Exclusion criteria for MRI o Claustrophobia/physical not able to lie in MR-s

Primary outcomes:
measure: Kidney allograft cortex oxygenation, T2*
timeFrame: T2* measured at baseline, 3 and 6 hours post-intervention
Secondary outcomes:
measure: Renal cortical perfusion, (ml/100g/min)
timeFrame: Renal cortical perfusion, measured at baseline, 3 and 6 hours post-intervention
Other outcomes:
measure: Renal allograft artery blood flow (ml/min)
timeFrame: Renal allograft artery blood flow measured at baseline, 3 and 6 hours post-intervention
measure: Blood glucose (mmol/L)
timeFrame: Blood glucose, measured at baseline, 3 and 6 hours post-intervention
measure: Blood pressure
timeFrame: Bloodpressure measured at baseline, 3 and 6 hours post-intervention
Locations:
city: Odense C
country: Denmark
facility: Department of Nephrology, Odense University Hospital Kløvervænget 6, Enterance 93, 3. floor
Study officials:
affiliation: Department of Nephrology, Odense University Hospital
name: Lotte B Lange, MD
role: PRINCIPAL_INVESTIGATOR
References: