Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension

Phase 4

Recruiting

• Conditions: Kidney Transplantation Recipients; Magnetic Resonance Imaging (MRI); Sodium-Glucose Transporter 2 Inhibitors; Non-Diabetic Patients; Randomized Controlled Trial; Placebo Control Design
• Interventions: Drug: JARDIANCE 25mg; Drug: Placebo

• Registration Number: NCT06933355
• Lead Sponsor: Odense University Hospital

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.

Study Timeline

• Study Start: 2025-03-27
• Status Verified: 2025-04
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-15
• Last Update Submitted: 2025-04-15
• Study First Posted: 2025-04-18
• Last Update Posted: 2025-04-18
• Primary Completion: 2026-04-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SGLT2i	JARDIANCE 25mg	Single dose of SGLT2i (Jardiance 50 mg)
Placebo	Placebo	Single dose placebo

Primary Outcome Measures

Name	Time	Method
Kidney allograft cortex oxygenation, T2*	T2* measured at baseline, 3 and 6 hours post-intervention	BOLD-MRI, T2\* cortex, s-1

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Department of Nephrology, Odense University Hospital Kløvervænget 6, Enterance 93, 3. floor; 🇩🇰 Odense C, Denmark